Materiały źródłowe

• #1 Chronic Lymphocytic Leukemia (CLL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/199313-overview

  Some patients die rapidly, within 2-3 years of diagnosis, because of complications from CLL. […] In most patients CLL initially has a relatively benign course, but eventually enters a progressive, treatment-resistant phase. During this later phase, morbidity is considerable, both from the disease and from complications of therapy. […] With the advances in treatment of CLL in recent decades, prolonged survival is possible. However, treatment rarely cures CLL, and mortality rates in patients with CLL remain significantly higher than in the general population. […] Prognosis depends on the disease stage at diagnosis as well as the presence or absence of high-risk markers. […] Given the recent advancements in CLL treatment, the Rai and Binet staging systems do not provide sufficient utility to estimate prognosis. The most accurate prognostic score currently utilized by oncologists is the CLL International Prognostic Index (CLL-IPI), which relies on five independent prognostic factors: Patient age, Clinical stage (Rai or Binet), Serum B2 microglobulin level, Mutational status of immunoglobulin heavy chain variable (IGVH), 17p deletion and/or TP53 mutation.

• #2 The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

  https://www.mdpi.com/2075-4418/11/5/853

  The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. […] Prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. […] In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients. […] CLL has long been known to be an extremely clinically heterogeneous disease that can be linked by the vast genetic heterogeneity observed in patients through optimal sequencing strategies. […] In the last decades, the improved understanding of CLL pathogenesis has resulted into the identification of a great number of prognostic markers (clinical systems, serum markers, genetic alterations, etc.), significantly improving patient stratification.

• #3 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A prognosis is the doctor’s best estimate of how cancer will affect you and how it will respond to treatment. Survival is the percentage of people with a disease who are alive at some point in time after their diagnosis. Prognosis and survival depend on many factors. […] The following are prognostic and predictive factors for chronic lymphocytic leukemia (CLL). […] CLL that has a chromosome 13 deletion with no other chromosome changes means a better prognosis. […] A chromosome 11 deletion is associated with the loss of the ATM gene. It predicts a decreased response to chemotherapy, so knowing this helps with planning treatment. […] Trisomy 12 (having an extra copy of chromosome 12) is associated with an intermediate prognosis. […] CLL with a 17p chromosome deletion (often written as „del(17p)”) doesn’t respond well to chemotherapy, so it has a poor prognosis.

• #4 The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

  https://www.mdpi.com/2075-4418/11/5/853

  The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. […] Prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. […] In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients. […] CLL has long been known to be an extremely clinically heterogeneous disease that can be linked by the vast genetic heterogeneity observed in patients through optimal sequencing strategies. […] In the last decades, the improved understanding of CLL pathogenesis has resulted into the identification of a great number of prognostic markers (clinical systems, serum markers, genetic alterations, etc.), significantly improving patient stratification.

• #5 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team. […] The presentation and course of CLL is strikingly varied in patients, with some individuals presenting with a biologically indolent course whereas others present with an aggressive course. Hence, it is imperative to get information about individual patient prognosis in order to define a therapeutic strategy and to allow patients to plan their lives moving forward. It is important to understand that these prognostic factors were developed and studied in the era of chemoimmunotherapy. Novel targeted inhibitors, such as ibrutinib and venetoclax, have improved the overall outcomes and landscape in CLL, although the follow-up is limited. Hence, our understanding of prognostic factors in the era of novel inhibitors is still evolving.

• #6 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team. […] The presentation and course of CLL is strikingly varied in patients, with some individuals presenting with a biologically indolent course whereas others present with an aggressive course. Hence, it is imperative to get information about individual patient prognosis in order to define a therapeutic strategy and to allow patients to plan their lives moving forward. It is important to understand that these prognostic factors were developed and studied in the era of chemoimmunotherapy. Novel targeted inhibitors, such as ibrutinib and venetoclax, have improved the overall outcomes and landscape in CLL, although the follow-up is limited. Hence, our understanding of prognostic factors in the era of novel inhibitors is still evolving.

• #7 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  CD38 immunophenotype. CD38 positivity (30%) correlates with a worse prognosis, but there is a 30% false-positive rate and a 50% false-negative rate using IGH mutational status as the gold standard for prognosis. […] Other malignancies. Patients with CLL are also at increased risk of developing other malignancies, even before therapy. […] An international prognostic index for CLL (CLL-IPI) identified four prognostic subgroups based on IGH mutational status, clinical stage, age (65 years vs. 65 years), and TP53 status (no abnormalities vs. del(17p), TP53 variant, or both). […] Any new prognostic model, and even the commonly used CLL-IPI, may be outdated because of the use of highly effective frontline therapies, including BCL2 inhibitors and BTK inhibitors. Revalidation of these prognostic models will be required.

• #8 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #9 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #10 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A prognosis is the doctor’s best estimate of how cancer will affect you and how it will respond to treatment. Survival is the percentage of people with a disease who are alive at some point in time after their diagnosis. Prognosis and survival depend on many factors. […] The following are prognostic and predictive factors for chronic lymphocytic leukemia (CLL). […] CLL that has a chromosome 13 deletion with no other chromosome changes means a better prognosis. […] A chromosome 11 deletion is associated with the loss of the ATM gene. It predicts a decreased response to chemotherapy, so knowing this helps with planning treatment. […] Trisomy 12 (having an extra copy of chromosome 12) is associated with an intermediate prognosis. […] CLL with a 17p chromosome deletion (often written as „del(17p)”) doesn’t respond well to chemotherapy, so it has a poor prognosis.

• #11 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #12 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A prognosis is the doctor’s best estimate of how cancer will affect you and how it will respond to treatment. Survival is the percentage of people with a disease who are alive at some point in time after their diagnosis. Prognosis and survival depend on many factors. […] The following are prognostic and predictive factors for chronic lymphocytic leukemia (CLL). […] CLL that has a chromosome 13 deletion with no other chromosome changes means a better prognosis. […] A chromosome 11 deletion is associated with the loss of the ATM gene. It predicts a decreased response to chemotherapy, so knowing this helps with planning treatment. […] Trisomy 12 (having an extra copy of chromosome 12) is associated with an intermediate prognosis. […] CLL with a 17p chromosome deletion (often written as „del(17p)”) doesn’t respond well to chemotherapy, so it has a poor prognosis.

• #13 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #14 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A prognosis is the doctor’s best estimate of how cancer will affect you and how it will respond to treatment. Survival is the percentage of people with a disease who are alive at some point in time after their diagnosis. Prognosis and survival depend on many factors. […] The following are prognostic and predictive factors for chronic lymphocytic leukemia (CLL). […] CLL that has a chromosome 13 deletion with no other chromosome changes means a better prognosis. […] A chromosome 11 deletion is associated with the loss of the ATM gene. It predicts a decreased response to chemotherapy, so knowing this helps with planning treatment. […] Trisomy 12 (having an extra copy of chromosome 12) is associated with an intermediate prognosis. […] CLL with a 17p chromosome deletion (often written as „del(17p)”) doesn’t respond well to chemotherapy, so it has a poor prognosis.

• #15 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #16 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A prognosis is the doctor’s best estimate of how cancer will affect you and how it will respond to treatment. Survival is the percentage of people with a disease who are alive at some point in time after their diagnosis. Prognosis and survival depend on many factors. […] The following are prognostic and predictive factors for chronic lymphocytic leukemia (CLL). […] CLL that has a chromosome 13 deletion with no other chromosome changes means a better prognosis. […] A chromosome 11 deletion is associated with the loss of the ATM gene. It predicts a decreased response to chemotherapy, so knowing this helps with planning treatment. […] Trisomy 12 (having an extra copy of chromosome 12) is associated with an intermediate prognosis. […] CLL with a 17p chromosome deletion (often written as „del(17p)”) doesn’t respond well to chemotherapy, so it has a poor prognosis.

• #17 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  Del (17p) which results in the loss of TP53, is the most important prognostic marker in CLL and is associated with poor outcomes, rapid disease progression and is historically associated with resistance to standard fludarabine-based chemoimmunotherapy. This chromosomal aberration is rare at diagnosis (less than 10%) but is more common in previously-treated patients. This underscores the importance of retesting for this aberration at clinical progression since it has therapeutic implications. 80% of patients with Del (17p) harbor mutations of the remaining TP53 allele. However, 4-5% of CLL patients carry a TP53 mutation in the absence of del (17p). These patients also carry a poor prognosis akin to patients with del (17p). This iterates to the fact that patients should undergo testing for TP53 mutation in addition to standard FISH testing for Del(17p). Patients with del(17p) or TP53 mutation respond well to targeted inhibitors of the B-cell receptor pathway and BCL-2 pathway, such as Ibrutinib and venetoclax respectively. Hence patients with these aberrations at diagnosis or progression are treated with these targeted inhibitors.

• #18 Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia | BMC Bioinformatics | Full Text

  https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-11-S9-S5

  Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It is a highly heterogeneous disease, and can be divided roughly into indolent and progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH) mutational status was found to be associated with patient survival outcome, and biomarkers linked to the IgVH status has been a focus in the CLL prognosis research field. However, biomarkers highly correlated with IgVH mutational status which can accurately predict the survival outcome are yet to be discovered. […] We have identified a set of genes that are potential CLL prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient IgVH mutational status with high accuracies. Their prognostic capabilities were cross-validated by applying these biomarker candidates to classify patients into different outcome groups using a CLL microarray datasets with clinical information.

• #19 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #20 Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11009732/

  Accurate long-term prognosis in CLL is a challenge. Existing prognostic models, such as the CLL-IPI, are limited as they provide predictions based on a single time point, typically at diagnosis, without taking into account years already survived. This limitation hinders effective disease management and appropriate counseling of CLL patients. […] With a mean post-diagnostic follow-up of 7.3 years, we observed a constant 5-year CS of approximately 75% for the entire patient cohort, demonstrating stable survival over a period of up to 10 years. […] Notably, CS remained remarkably stable regardless of age at diagnosis, although patients older than 65 years exhibited approximately 20% lower CS likelihood. […] The much less favorable prognosis of patients with an unmutated IGHV locus and the marked deterioration over time (CS decreases by approximately 30% over 10 years) not seen in IGHV-mutated patients reflect the heterogeneity of CLL and the fundamental biological differences of the disease associated with the IGHV mutation status.

• #21 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Prognostic markers help stratify patients in clinical trials, assess the need for therapy, and select the type of therapy. Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, and CD38 immunophenotype. […] Prognostic markers include the following: IGH pathogenic variant. The finding of significant numbers of variants in this region is associated with a median survival in excess of 20 to 25 years. The absence of variants is associated with a median survival of 8 to 10 years. […] FISH test results. FISH chromosomal abnormalities were associated with prognosis in retrospective and prospective studies, and clonal evolution has been seen over time. The following chromosomal abnormalities have been reported: del(13q) is a favorable prognostic marker (median overall survival [OS], 17 years in one prospective study). Trisomy 12 and del(11) have a less favorable prognosis (median OS, 9-11 years in one prospective study). del(17p) is associated with TP53 pathogenic variants, poor response rates, and short duration of response to the standard therapeutic options. del(17p) is associated with the most unfavorable prognosis (median OS, 7 years in one prospective trial).

• #22 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #23 Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11009732/

  Accurate long-term prognosis in CLL is a challenge. Existing prognostic models, such as the CLL-IPI, are limited as they provide predictions based on a single time point, typically at diagnosis, without taking into account years already survived. This limitation hinders effective disease management and appropriate counseling of CLL patients. […] With a mean post-diagnostic follow-up of 7.3 years, we observed a constant 5-year CS of approximately 75% for the entire patient cohort, demonstrating stable survival over a period of up to 10 years. […] Notably, CS remained remarkably stable regardless of age at diagnosis, although patients older than 65 years exhibited approximately 20% lower CS likelihood. […] The much less favorable prognosis of patients with an unmutated IGHV locus and the marked deterioration over time (CS decreases by approximately 30% over 10 years) not seen in IGHV-mutated patients reflect the heterogeneity of CLL and the fundamental biological differences of the disease associated with the IGHV mutation status.

• #24

  https://link.springer.com/article/10.1007/s00277-024-05627-w

  Notably, CS remained remarkably stable regardless of age at diagnosis, although patients older than 65 years exhibited approximately 20% lower CS likelihood. […] These data suggest that the probability of surviving additional 5 years remains at 75% or slightly below over the disease course, indicating that CLL patients face a constant risk of death with each additional year of survival. […] For IGHV mutation status, our CS analyses revealed a clinically meaningful and significant separation of subgroups. […] The much less favorable prognosis of patients with an unmutated IGHV locus and the marked deterioration over time (CS decreases by approximately 30% over 10 years) not seen in IGHV-mutated patients reflect the heterogeneity of CLL and the fundamental biological differences of the disease associated with the IGHV mutation status.

• #25 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. […] We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. […] Our results provide a springboard to indepth functional validation of putative drivers and our integrated genome-wide approach could, after independent clinical validation, refine current clinical outcome prediction. […] Thus far, only mutations in TP53 influence clinical practice. […] Other prognostic markers, including the immunoglobulin heavy chain variable (IGHV) region mutational status, and existing molecular classifications have limited predictive value in individual patients.

• #26 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  Del (17p) which results in the loss of TP53, is the most important prognostic marker in CLL and is associated with poor outcomes, rapid disease progression and is historically associated with resistance to standard fludarabine-based chemoimmunotherapy. This chromosomal aberration is rare at diagnosis (less than 10%) but is more common in previously-treated patients. This underscores the importance of retesting for this aberration at clinical progression since it has therapeutic implications. 80% of patients with Del (17p) harbor mutations of the remaining TP53 allele. However, 4-5% of CLL patients carry a TP53 mutation in the absence of del (17p). These patients also carry a poor prognosis akin to patients with del (17p). This iterates to the fact that patients should undergo testing for TP53 mutation in addition to standard FISH testing for Del(17p). Patients with del(17p) or TP53 mutation respond well to targeted inhibitors of the B-cell receptor pathway and BCL-2 pathway, such as Ibrutinib and venetoclax respectively. Hence patients with these aberrations at diagnosis or progression are treated with these targeted inhibitors.

• #27 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  Del (17p) which results in the loss of TP53, is the most important prognostic marker in CLL and is associated with poor outcomes, rapid disease progression and is historically associated with resistance to standard fludarabine-based chemoimmunotherapy. This chromosomal aberration is rare at diagnosis (less than 10%) but is more common in previously-treated patients. This underscores the importance of retesting for this aberration at clinical progression since it has therapeutic implications. 80% of patients with Del (17p) harbor mutations of the remaining TP53 allele. However, 4-5% of CLL patients carry a TP53 mutation in the absence of del (17p). These patients also carry a poor prognosis akin to patients with del (17p). This iterates to the fact that patients should undergo testing for TP53 mutation in addition to standard FISH testing for Del(17p). Patients with del(17p) or TP53 mutation respond well to targeted inhibitors of the B-cell receptor pathway and BCL-2 pathway, such as Ibrutinib and venetoclax respectively. Hence patients with these aberrations at diagnosis or progression are treated with these targeted inhibitors.

• #28

  https://haematologica.org/article/view/9598

  A significantly lower overall response rate was found only for TP53 mutated cases (HR 5.20,P0.01). In univariate analysis, significantly decreased PFS was found for patients with mutations in TP53 (HR 2.02,P0.01), SF3B1 (HR 1.66,P0.01), and NOTCH1 (HR 1.39, P=0.03), but not for patients with mutations in ATM (HR 1.16,P=0.42) or BIRC3 (HR 1.63, P=0.23). […] Notably, this correlation was observed despite the high degree of collinearity with 17p deletion, confirming the need of TP53 mutation testing in addition to 17p deletion diagnostics in routine practice, as recommended by current ERIC and International Workshop on CLL (iwCLL) guidelines.

• #29

  https://haematologica.org/article/view/9598

  Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. […] While most mutations lacked prognostic significance, TP53 (HR2.02,p0.01), SF3B1 (HR1.66,p=0.01) and NOTCH1 (HR1.39,p=0.03) were associated with inferior PFS in univariate analysis. Multivariate analysis confirmed the independent prognostic role of TP53 for PFS (HR1.71,p=0.04) and OS (HR2.78,p=0.02) and of SF3B1 for PFS only (HR1.52,p=0.02). […] In summary, TP53 and SF3B1 were confirmed as independent prognostic and NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial.

• #30

  https://haematologica.org/article/view/9598

  A significantly lower overall response rate was found only for TP53 mutated cases (HR 5.20,P0.01). In univariate analysis, significantly decreased PFS was found for patients with mutations in TP53 (HR 2.02,P0.01), SF3B1 (HR 1.66,P0.01), and NOTCH1 (HR 1.39, P=0.03), but not for patients with mutations in ATM (HR 1.16,P=0.42) or BIRC3 (HR 1.63, P=0.23). […] Notably, this correlation was observed despite the high degree of collinearity with 17p deletion, confirming the need of TP53 mutation testing in addition to 17p deletion diagnostics in routine practice, as recommended by current ERIC and International Workshop on CLL (iwCLL) guidelines.

• #31 The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

  https://www.mdpi.com/2075-4418/11/5/853

  The Rai and Binet staging systems still remain as the backbone of prognostication due to their simplicity and low cost. […] However, these staging systems have limited power to predict the evolution of the disease and response to therapy. […] The presence of 13q deletion has been associated with a favorable outcome, while the 11q and 17p deletions have been related to worse outcomes. […] The assessment of the TP53 status is crucial to predict the clinical outcome and therapy response, as its alterations contribute to a poor prognosis and chemotherapy resistance. […] The expansion of next-generation sequencing (NGS) has contributed to get a deep insight into the mechanisms of the pathogenesis of CLL. […] Several studies have demonstrated the prognostic impact of some of these genetic alterations in the time to first treatment (TTFT), progression-free survival (PFS) and overall survival (OS).

• #32

  https://haematologica.org/article/view/9598

  Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. […] While most mutations lacked prognostic significance, TP53 (HR2.02,p0.01), SF3B1 (HR1.66,p=0.01) and NOTCH1 (HR1.39,p=0.03) were associated with inferior PFS in univariate analysis. Multivariate analysis confirmed the independent prognostic role of TP53 for PFS (HR1.71,p=0.04) and OS (HR2.78,p=0.02) and of SF3B1 for PFS only (HR1.52,p=0.02). […] In summary, TP53 and SF3B1 were confirmed as independent prognostic and NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial.

• #33

  https://haematologica.org/article/view/9598

  A significantly lower overall response rate was found only for TP53 mutated cases (HR 5.20,P0.01). In univariate analysis, significantly decreased PFS was found for patients with mutations in TP53 (HR 2.02,P0.01), SF3B1 (HR 1.66,P0.01), and NOTCH1 (HR 1.39, P=0.03), but not for patients with mutations in ATM (HR 1.16,P=0.42) or BIRC3 (HR 1.63, P=0.23). […] Notably, this correlation was observed despite the high degree of collinearity with 17p deletion, confirming the need of TP53 mutation testing in addition to 17p deletion diagnostics in routine practice, as recommended by current ERIC and International Workshop on CLL (iwCLL) guidelines.

• #34

  https://haematologica.org/article/view/9598

  Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. […] While most mutations lacked prognostic significance, TP53 (HR2.02,p0.01), SF3B1 (HR1.66,p=0.01) and NOTCH1 (HR1.39,p=0.03) were associated with inferior PFS in univariate analysis. Multivariate analysis confirmed the independent prognostic role of TP53 for PFS (HR1.71,p=0.04) and OS (HR2.78,p=0.02) and of SF3B1 for PFS only (HR1.52,p=0.02). […] In summary, TP53 and SF3B1 were confirmed as independent prognostic and NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial.

• #35

  https://haematologica.org/article/view/9598

  A significantly lower overall response rate was found only for TP53 mutated cases (HR 5.20,P0.01). In univariate analysis, significantly decreased PFS was found for patients with mutations in TP53 (HR 2.02,P0.01), SF3B1 (HR 1.66,P0.01), and NOTCH1 (HR 1.39, P=0.03), but not for patients with mutations in ATM (HR 1.16,P=0.42) or BIRC3 (HR 1.63, P=0.23). […] Notably, this correlation was observed despite the high degree of collinearity with 17p deletion, confirming the need of TP53 mutation testing in addition to 17p deletion diagnostics in routine practice, as recommended by current ERIC and International Workshop on CLL (iwCLL) guidelines.

• #36 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  Our results provide a springboard to indepth functional validation of putative drivers and our integrated genome-wide approach could, after independent clinical validation, refine current clinical outcome prediction. […] Restricting analysis to patients with information on long-term survival outcome, 13 known or putative drivers and recurrent CNAs were significantly associated with progression-free survival (PFS) and 11 with overall survival (OS). […] Out of the 22 putative drivers, 21 were also related to disease progression. […] Mutations showed evidence of clonal expansion in more advanced disease and altered RNA expression. […] This gene contributes to the differentiation of immature B-cells and is associated with a familial form of common variable immunodeficiency disorder. […] Similarly, SMCHD1 mutations showed clonal expansion and were associated with adverse OS.

• #37 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. […] We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. […] Our results provide a springboard to indepth functional validation of putative drivers and our integrated genome-wide approach could, after independent clinical validation, refine current clinical outcome prediction. […] Thus far, only mutations in TP53 influence clinical practice. […] Other prognostic markers, including the immunoglobulin heavy chain variable (IGHV) region mutational status, and existing molecular classifications have limited predictive value in individual patients.

• #38 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Other prognostic factors include the following: Anemia and thrombocytopenia. These are important adverse prognostic variables, but only if due to extensive marrow involvement by CLL. Autoimmune hemolytic anemia and immune thrombocytopenic purpura do not confer a worse prognosis. Age. CLL occurs primarily in middle-aged and older adults, with worse prognosis in successive decades of life. Stage. […] Positron emission tomography (PET)-CT scan results. This test should only be used in the context of recurrent fever, soaking night sweats, weight loss (10% baseline weight in 6 months), or rapidly growing lymph nodes, because these findings might herald histological transformation to a diffuse large B-cell lymphoma (DLBCL) (so-called Richter transformation). […] Lymphocyte doubling time. Doubling of the white blood cell count in less than 1 year implies a worse prognosis.

• #39 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #40 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Other prognostic factors include the following: Anemia and thrombocytopenia. These are important adverse prognostic variables, but only if due to extensive marrow involvement by CLL. Autoimmune hemolytic anemia and immune thrombocytopenic purpura do not confer a worse prognosis. Age. CLL occurs primarily in middle-aged and older adults, with worse prognosis in successive decades of life. Stage. […] Positron emission tomography (PET)-CT scan results. This test should only be used in the context of recurrent fever, soaking night sweats, weight loss (10% baseline weight in 6 months), or rapidly growing lymph nodes, because these findings might herald histological transformation to a diffuse large B-cell lymphoma (DLBCL) (so-called Richter transformation). […] Lymphocyte doubling time. Doubling of the white blood cell count in less than 1 year implies a worse prognosis.

• #41 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #42 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #43 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #44 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #45 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Other prognostic factors include the following: Anemia and thrombocytopenia. These are important adverse prognostic variables, but only if due to extensive marrow involvement by CLL. Autoimmune hemolytic anemia and immune thrombocytopenic purpura do not confer a worse prognosis. Age. CLL occurs primarily in middle-aged and older adults, with worse prognosis in successive decades of life. Stage. […] Positron emission tomography (PET)-CT scan results. This test should only be used in the context of recurrent fever, soaking night sweats, weight loss (10% baseline weight in 6 months), or rapidly growing lymph nodes, because these findings might herald histological transformation to a diffuse large B-cell lymphoma (DLBCL) (so-called Richter transformation). […] Lymphocyte doubling time. Doubling of the white blood cell count in less than 1 year implies a worse prognosis.

• #46 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Other prognostic factors include the following: Anemia and thrombocytopenia. These are important adverse prognostic variables, but only if due to extensive marrow involvement by CLL. Autoimmune hemolytic anemia and immune thrombocytopenic purpura do not confer a worse prognosis. Age. CLL occurs primarily in middle-aged and older adults, with worse prognosis in successive decades of life. Stage. […] Positron emission tomography (PET)-CT scan results. This test should only be used in the context of recurrent fever, soaking night sweats, weight loss (10% baseline weight in 6 months), or rapidly growing lymph nodes, because these findings might herald histological transformation to a diffuse large B-cell lymphoma (DLBCL) (so-called Richter transformation). […] Lymphocyte doubling time. Doubling of the white blood cell count in less than 1 year implies a worse prognosis.

• #47 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Beta-2-microglobulin. Higher levels imply a worse prognosis. […] Richter transformation. In 2% to 10% of patients, CLL will transform into a more aggressive lymphoma, termed Richter transformation. This is usually a DLBCL of the more aggressive activated B-cell subtype. The prognosis is similar to de novo presentations of DLBCL when the CLL has never required therapy or when there is no clonal connection between the CLL and DLBCL. However, the prognosis is poor (median survival, 6-14 months) for most patients with Richter transformation to DLBCL when there has been prior therapy for CLL with chemoimmunotherapy, Bruton tyrosine kinase (BTK) inhibitors, and/or venetoclax. […] Clearance of measurable residual disease (MRD). The improvements in response rates from more intensive regimens have maximized the clearance of MRD. In one prospective trial of 493 patients, clearance of MRD was an independent predictor of OS by multivariate analysis.

• #48 Prognosis and survival for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival

  A mutation, or change, of the TP53 gene is also associated with a 17p chromosome deletion. CLL with mutated TP53 doesn’t respond well to chemotherapy, so it has a poor prognosis. […] CLL with an unmutated, or unchanged, gene for IGHV (immunoglobulin heavy chain variable region) is often more aggressive and requires treatment right away. CLL with an unmutated IGHV gene does not respond well to chemotherapy. It has a poor prognosis. […] A protein level in the blood of less than 3.5 beta-2-microglobulin means a better prognosis. […] People 70 years old and older have a poorer prognosis. […] CLL that is at a lower stage (stage 0 or 1) at the time of diagnosis has a better prognosis. […] People with a good performance status at the time of diagnosis have a better prognosis. […] Men have a worse prognosis than women when diagnosed with CLL. […] CLL with a lymphocyte doubling time of more than 1 year has a better prognosis. […] The CLL International Prognostic Index (CLL-IPI) helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat CLL.

• #49 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Beta-2-microglobulin. Higher levels imply a worse prognosis. […] Richter transformation. In 2% to 10% of patients, CLL will transform into a more aggressive lymphoma, termed Richter transformation. This is usually a DLBCL of the more aggressive activated B-cell subtype. The prognosis is similar to de novo presentations of DLBCL when the CLL has never required therapy or when there is no clonal connection between the CLL and DLBCL. However, the prognosis is poor (median survival, 6-14 months) for most patients with Richter transformation to DLBCL when there has been prior therapy for CLL with chemoimmunotherapy, Bruton tyrosine kinase (BTK) inhibitors, and/or venetoclax. […] Clearance of measurable residual disease (MRD). The improvements in response rates from more intensive regimens have maximized the clearance of MRD. In one prospective trial of 493 patients, clearance of MRD was an independent predictor of OS by multivariate analysis.

• #50 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Beta-2-microglobulin. Higher levels imply a worse prognosis. […] Richter transformation. In 2% to 10% of patients, CLL will transform into a more aggressive lymphoma, termed Richter transformation. This is usually a DLBCL of the more aggressive activated B-cell subtype. The prognosis is similar to de novo presentations of DLBCL when the CLL has never required therapy or when there is no clonal connection between the CLL and DLBCL. However, the prognosis is poor (median survival, 6-14 months) for most patients with Richter transformation to DLBCL when there has been prior therapy for CLL with chemoimmunotherapy, Bruton tyrosine kinase (BTK) inhibitors, and/or venetoclax. […] Clearance of measurable residual disease (MRD). The improvements in response rates from more intensive regimens have maximized the clearance of MRD. In one prospective trial of 493 patients, clearance of MRD was an independent predictor of OS by multivariate analysis.

• #51 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Beta-2-microglobulin. Higher levels imply a worse prognosis. […] Richter transformation. In 2% to 10% of patients, CLL will transform into a more aggressive lymphoma, termed Richter transformation. This is usually a DLBCL of the more aggressive activated B-cell subtype. The prognosis is similar to de novo presentations of DLBCL when the CLL has never required therapy or when there is no clonal connection between the CLL and DLBCL. However, the prognosis is poor (median survival, 6-14 months) for most patients with Richter transformation to DLBCL when there has been prior therapy for CLL with chemoimmunotherapy, Bruton tyrosine kinase (BTK) inhibitors, and/or venetoclax. […] Clearance of measurable residual disease (MRD). The improvements in response rates from more intensive regimens have maximized the clearance of MRD. In one prospective trial of 493 patients, clearance of MRD was an independent predictor of OS by multivariate analysis.

• #52 Machine learning can identify newly diagnosed patients with CLL at high risk of infection | Nature Communications

  https://www.nature.com/articles/s41467-019-14225-8

  Infections have become the major cause of morbidity and mortality among patients with chronic lymphocytic leukemia (CLL) due to immune dysfunction and cytotoxic CLL treatment. […] Predictive models for identifying these patients are warranted, since prognostic factors for infections in CLL prior to and upon CLL treatment are largely unknown. […] The first step in changing the natural history of CLL-induced immune dysfunction is thus to identify patients at risk of infection or CLL treatment at time of diagnosis. […] CLL-TIM identifies patients at risk of severe infection or CLL treatment within 2-years of CLL diagnosis with high precision (0.72 CI95%: 0.630.81) and recall (0.75 CI95%: 0.650.86). […] CLL-TIM predicted infection and CLL treatment with similar frequencies as first events, thus validating the ability of CLL-TIM to identify both patients at risk of infection and in need of CLL treatment.

• #53

  https://link.springer.com/article/10.1007/s00277-024-05625-y

  Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. […] The mortality rate due to infections ranges from 30 to 50%. Moreover, patients with a history of infections within the first year after diagnosis have exhibited lower overall survival. […] In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients. […] The median TTFI for the entire cohort was not reached at 25 years. Patients older than 65 had a shorter TTFI with a median of 15.4 years.

• #54

  https://link.springer.com/article/10.1007/s00277-024-05625-y

  Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. […] The mortality rate due to infections ranges from 30 to 50%. Moreover, patients with a history of infections within the first year after diagnosis have exhibited lower overall survival. […] In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients. […] The median TTFI for the entire cohort was not reached at 25 years. Patients older than 65 had a shorter TTFI with a median of 15.4 years.

• #55 Machine learning can identify newly diagnosed patients with CLL at high risk of infection | Nature Communications

  https://www.nature.com/articles/s41467-019-14225-8

  The correlation between immune dysfunction in CLL and aggressive disease is in accordance with recent reports of inferior survival and TTFT for CLL patients suffering from infection within the first year of diagnosis. […] CLL-IPI was developed for prediction of OS and validated for TTFT but performed poorly for prediction of infection. […] Thus, approaching CLL modeling with a larger and more heterogeneous set of features, together with the addition of infection as an outcome, were necessary to improve overall detection.

• #56 Machine learning can identify newly diagnosed patients with CLL at high risk of infection | Nature Communications

  https://www.nature.com/articles/s41467-019-14225-8

  Infections have become the major cause of morbidity and mortality among patients with chronic lymphocytic leukemia (CLL) due to immune dysfunction and cytotoxic CLL treatment. […] Predictive models for identifying these patients are warranted, since prognostic factors for infections in CLL prior to and upon CLL treatment are largely unknown. […] The first step in changing the natural history of CLL-induced immune dysfunction is thus to identify patients at risk of infection or CLL treatment at time of diagnosis. […] CLL-TIM identifies patients at risk of severe infection or CLL treatment within 2-years of CLL diagnosis with high precision (0.72 CI95%: 0.630.81) and recall (0.75 CI95%: 0.650.86). […] CLL-TIM predicted infection and CLL treatment with similar frequencies as first events, thus validating the ability of CLL-TIM to identify both patients at risk of infection and in need of CLL treatment.

• #57 Chronic Lymphocytic Leukemia (CLL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/199313-overview

  Some patients die rapidly, within 2-3 years of diagnosis, because of complications from CLL. […] In most patients CLL initially has a relatively benign course, but eventually enters a progressive, treatment-resistant phase. During this later phase, morbidity is considerable, both from the disease and from complications of therapy. […] With the advances in treatment of CLL in recent decades, prolonged survival is possible. However, treatment rarely cures CLL, and mortality rates in patients with CLL remain significantly higher than in the general population. […] Prognosis depends on the disease stage at diagnosis as well as the presence or absence of high-risk markers. […] Given the recent advancements in CLL treatment, the Rai and Binet staging systems do not provide sufficient utility to estimate prognosis. The most accurate prognostic score currently utilized by oncologists is the CLL International Prognostic Index (CLL-IPI), which relies on five independent prognostic factors: Patient age, Clinical stage (Rai or Binet), Serum B2 microglobulin level, Mutational status of immunoglobulin heavy chain variable (IGVH), 17p deletion and/or TP53 mutation.

• #58 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  CD38 immunophenotype. CD38 positivity (30%) correlates with a worse prognosis, but there is a 30% false-positive rate and a 50% false-negative rate using IGH mutational status as the gold standard for prognosis. […] Other malignancies. Patients with CLL are also at increased risk of developing other malignancies, even before therapy. […] An international prognostic index for CLL (CLL-IPI) identified four prognostic subgroups based on IGH mutational status, clinical stage, age (65 years vs. 65 years), and TP53 status (no abnormalities vs. del(17p), TP53 variant, or both). […] Any new prognostic model, and even the commonly used CLL-IPI, may be outdated because of the use of highly effective frontline therapies, including BCL2 inhibitors and BTK inhibitors. Revalidation of these prognostic models will be required.

• #59 Chronic Lymphocytic Leukemia (CLL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/199313-overview

  Some patients die rapidly, within 2-3 years of diagnosis, because of complications from CLL. […] In most patients CLL initially has a relatively benign course, but eventually enters a progressive, treatment-resistant phase. During this later phase, morbidity is considerable, both from the disease and from complications of therapy. […] With the advances in treatment of CLL in recent decades, prolonged survival is possible. However, treatment rarely cures CLL, and mortality rates in patients with CLL remain significantly higher than in the general population. […] Prognosis depends on the disease stage at diagnosis as well as the presence or absence of high-risk markers. […] Given the recent advancements in CLL treatment, the Rai and Binet staging systems do not provide sufficient utility to estimate prognosis. The most accurate prognostic score currently utilized by oncologists is the CLL International Prognostic Index (CLL-IPI), which relies on five independent prognostic factors: Patient age, Clinical stage (Rai or Binet), Serum B2 microglobulin level, Mutational status of immunoglobulin heavy chain variable (IGVH), 17p deletion and/or TP53 mutation.

• #60 Chronic Lymphocytic Leukemia (CLL): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/199313-overview

  Patients are deemed low-, intermediate-, high-, or very high risk depending on the presence or absence of the prognostic factors. Low-risk patients have over a 90% chance of 5-year overall survival and, therefore, treatment is not recommended. Intermediate-risk patients have a nearly 90% chance of 5-year overall survival and are treated only if they are symptomatic. High-risk patients are managed similarly to intermediate-risk patients, but they have a slightly lower chance of 5-year overall survival at 63%. Very high-risk patients are treated with targeted agents.

• #61 Survival for chronic lymphocytic leukaemia | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/survival

  Although this prognostic index is quite recent, treatment continues to change. Doctors are using new targeted drugs to treat CLL. These might improve the outlook for some people. […] Doctors generally still think this index is a useful tool to help predict prognosis. […] Instead of survival by stage, we provide survival statistics from the Chronic Lymphocytic Leukaemia International Prognostic Index (CLL-IPI) study. […] Talk to your doctor about your prognosis. They might be able to tell you more about your risk group and your outlook. […] Please bear in mind that CLL treatment is improving as doctors use new targeted drugs. So people treated now might have a better outlook. […] Almost 95 out of 100 people (almost 95%) survive for 5 years or more after diagnosis. […] Around 80 out of 100 people (around 80%) survive for 5 years or more after diagnosis. […] Almost 65 out of 100 people (almost 65%) survive for 5 years or more after diagnosis. […] Almost 25 out of 100 people (almost 25%) survive for 5 years or more after diagnosis.

• #62 Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11009732/

  The composite prognostic score CLL-IPI, whose static prognostic significance we can excellently reproduce here in a real-world cohort outside clinical trials, shows a similar prognostic separation of CS over time with a 5-year survival rate ranging from a stable 95% (CLL-IPI=0) to a decline to 25% (CLL-IPI=2+3) over the 10-year observation period. […] Overall, we can demonstrate that CS is relevant for the management of CLL and the assessment of prognosis for physicians and patients. We confirm the previously reported stable prognosis of CLL patients over a long observation period and show that high-risk subgroups undergo dramatic and patient-relevant prognostic changes over time with gradually increasing mortality.

• #63

  https://link.springer.com/article/10.1007/s00277-024-05627-w

  The composite prognostic score CLL-IPI shows a similar prognostic separation of CS over time with a 5-year survival rate ranging from a stable 95% (CLL-IPI=0) to a decline to 25% (CLL-IPI=2+3) over the 10-year observation period. […] Overall, we can demonstrate that CS is relevant for the management of CLL and the assessment of prognosis for physicians and patients.

• #64 Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11009732/

  Accurate long-term prognosis in CLL is a challenge. Existing prognostic models, such as the CLL-IPI, are limited as they provide predictions based on a single time point, typically at diagnosis, without taking into account years already survived. This limitation hinders effective disease management and appropriate counseling of CLL patients. […] With a mean post-diagnostic follow-up of 7.3 years, we observed a constant 5-year CS of approximately 75% for the entire patient cohort, demonstrating stable survival over a period of up to 10 years. […] Notably, CS remained remarkably stable regardless of age at diagnosis, although patients older than 65 years exhibited approximately 20% lower CS likelihood. […] The much less favorable prognosis of patients with an unmutated IGHV locus and the marked deterioration over time (CS decreases by approximately 30% over 10 years) not seen in IGHV-mutated patients reflect the heterogeneity of CLL and the fundamental biological differences of the disease associated with the IGHV mutation status.

• #65 Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11009732/

  Biomarkers in chronic lymphocytic leukemia (CLL) allow assessment of prognosis. However, the validity of current prognostic biomarkers based on a single assessment point remains unclear for patients who have survived one or more years. Conditional survival (CS) studies that address how prognosis may change over time, especially in prognostic subgroups, are still rare. […] We demonstrate that 5-year CS probability is stable (app. 75%) for the entire CLL patient cohort over 10 years. While age, sex, and stage have no significant impact on CS, patients with high-risk disease features such as non-mutated IGHV, deletion 17p, and high-risk CLL-IPI have a significantly worse prognosis at diagnosis, and 5-year CS steadily decreases with each additional year survived. Our results confirm that CLL patients have a stable survival probability with excess mortality and that the prognosis of high-risk CLL patients declines over time. We infer that CS-based prognostic information is relevant for disease management and counseling of CLL patients.

• #66

  https://link.springer.com/article/10.1007/s00277-024-05627-w

  Biomarkers in chronic lymphocytic leukemia (CLL) allow assessment of prognosis. […] We demonstrate that 5-year CS probability is stable (app. 75%) for the entire CLL patient cohort over 10 years. […] Our results confirm that CLL patients have a stable survival probability with excess mortality and that the prognosis of high-risk CLL patients declines over time. […] Accurate long-term prognosis in CLL is a challenge. Existing prognostic models, such as the CLL-IPI, are limited as they provide predictions based on a single time point, typically at diagnosis, without taking into account years already survived. […] With a mean post-diagnostic follow-up of 7.3 years, we observed a constant 5-year CS of approximately 75% for the entire patient cohort, demonstrating stable survival over a period of up to 10 years.

• #67 Conditional survival to assess prognosis in patients with chronic lymphocytic leukemia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11009732/

  Biomarkers in chronic lymphocytic leukemia (CLL) allow assessment of prognosis. However, the validity of current prognostic biomarkers based on a single assessment point remains unclear for patients who have survived one or more years. Conditional survival (CS) studies that address how prognosis may change over time, especially in prognostic subgroups, are still rare. […] We demonstrate that 5-year CS probability is stable (app. 75%) for the entire CLL patient cohort over 10 years. While age, sex, and stage have no significant impact on CS, patients with high-risk disease features such as non-mutated IGHV, deletion 17p, and high-risk CLL-IPI have a significantly worse prognosis at diagnosis, and 5-year CS steadily decreases with each additional year survived. Our results confirm that CLL patients have a stable survival probability with excess mortality and that the prognosis of high-risk CLL patients declines over time. We infer that CS-based prognostic information is relevant for disease management and counseling of CLL patients.

• #68

  https://haematologica.org/article/view/haematol.2020.251561

  Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) can induce long-term remissions in patients with chronic lymphocytic leukemia. […] We identified a prognostic signature of less than a dozen genes, which substituted for established prognostic factors, including TP53 and IGHV gene mutation status. […] Independent prognostic impact was confirmed for treatment, 2-microglobulin and del(17p) regarding overall survival and for treatment, del(11q), del(17p) and SF3B1 mutation for progression-free survival. […] GEP variables showed higher prognostic accuracy for patients with long progression-free survival compared to categorical variables like the IGHV gene mutation status and reliably predicted overall survival in CLL8 and an independent cohort. […] GEP-based prognostic models can help to identify patients who specifically benefit from FCR treatment.

• #69

  https://haematologica.org/article/view/haematol.2020.251561

  Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) can induce long-term remissions in patients with chronic lymphocytic leukemia. […] We identified a prognostic signature of less than a dozen genes, which substituted for established prognostic factors, including TP53 and IGHV gene mutation status. […] Independent prognostic impact was confirmed for treatment, 2-microglobulin and del(17p) regarding overall survival and for treatment, del(11q), del(17p) and SF3B1 mutation for progression-free survival. […] GEP variables showed higher prognostic accuracy for patients with long progression-free survival compared to categorical variables like the IGHV gene mutation status and reliably predicted overall survival in CLL8 and an independent cohort. […] GEP-based prognostic models can help to identify patients who specifically benefit from FCR treatment.

• #70

  https://haematologica.org/article/view/haematol.2020.251561

  Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) can induce long-term remissions in patients with chronic lymphocytic leukemia. […] We identified a prognostic signature of less than a dozen genes, which substituted for established prognostic factors, including TP53 and IGHV gene mutation status. […] Independent prognostic impact was confirmed for treatment, 2-microglobulin and del(17p) regarding overall survival and for treatment, del(11q), del(17p) and SF3B1 mutation for progression-free survival. […] GEP variables showed higher prognostic accuracy for patients with long progression-free survival compared to categorical variables like the IGHV gene mutation status and reliably predicted overall survival in CLL8 and an independent cohort. […] GEP-based prognostic models can help to identify patients who specifically benefit from FCR treatment.

• #71

  https://haematologica.org/article/view/haematol.2020.251561

  Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) can induce long-term remissions in patients with chronic lymphocytic leukemia. […] We identified a prognostic signature of less than a dozen genes, which substituted for established prognostic factors, including TP53 and IGHV gene mutation status. […] Independent prognostic impact was confirmed for treatment, 2-microglobulin and del(17p) regarding overall survival and for treatment, del(11q), del(17p) and SF3B1 mutation for progression-free survival. […] GEP variables showed higher prognostic accuracy for patients with long progression-free survival compared to categorical variables like the IGHV gene mutation status and reliably predicted overall survival in CLL8 and an independent cohort. […] GEP-based prognostic models can help to identify patients who specifically benefit from FCR treatment.

• #72 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  A higher number of mutated genes was associated with worse PFS, especially when noncoding variants were included. […] Shorter telomeres were significantly enriched in samples with p53 pathway alterations and were associated with poorer PFS. […] The eight groups were associated with different PFS and OS, independent of TP53 status. […] Patients with both TP53 mutations and GC7/8 changes had ultrahigh-risk disease and fared worse compared with patients with TP53 mutations but no GC7/8 status. […] Our study presents the first comprehensive WGS analysis of a large series of CLL patients requiring treatment. […] Collectively, our study provides a springboard for downstream functional analyses of putative coding and noncoding drivers.

• #73 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  A higher number of mutated genes was associated with worse PFS, especially when noncoding variants were included. […] Shorter telomeres were significantly enriched in samples with p53 pathway alterations and were associated with poorer PFS. […] The eight groups were associated with different PFS and OS, independent of TP53 status. […] Patients with both TP53 mutations and GC7/8 changes had ultrahigh-risk disease and fared worse compared with patients with TP53 mutations but no GC7/8 status. […] Our study presents the first comprehensive WGS analysis of a large series of CLL patients requiring treatment. […] Collectively, our study provides a springboard for downstream functional analyses of putative coding and noncoding drivers.

• #74 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  A higher number of mutated genes was associated with worse PFS, especially when noncoding variants were included. […] Shorter telomeres were significantly enriched in samples with p53 pathway alterations and were associated with poorer PFS. […] The eight groups were associated with different PFS and OS, independent of TP53 status. […] Patients with both TP53 mutations and GC7/8 changes had ultrahigh-risk disease and fared worse compared with patients with TP53 mutations but no GC7/8 status. […] Our study presents the first comprehensive WGS analysis of a large series of CLL patients requiring treatment. […] Collectively, our study provides a springboard for downstream functional analyses of putative coding and noncoding drivers.

• #75 Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features | Nature Genetics

  https://www.nature.com/articles/s41588-022-01211-y

  A higher number of mutated genes was associated with worse PFS, especially when noncoding variants were included. […] Shorter telomeres were significantly enriched in samples with p53 pathway alterations and were associated with poorer PFS. […] The eight groups were associated with different PFS and OS, independent of TP53 status. […] Patients with both TP53 mutations and GC7/8 changes had ultrahigh-risk disease and fared worse compared with patients with TP53 mutations but no GC7/8 status. […] Our study presents the first comprehensive WGS analysis of a large series of CLL patients requiring treatment. […] Collectively, our study provides a springboard for downstream functional analyses of putative coding and noncoding drivers.

• #76 Survival for chronic lymphocytic leukaemia | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/survival

  Chronic lymphocytic leukaemia (CLL) often develops very slowly. You might need little or no treatment. Although it is not usually curable, the disease can be under control for many years. But CLL can progress more quickly in some people. This might mean you need treatment earlier or need many different courses of treatment. […] The outlook (prognosis) can vary. Some people live for many years. But for some, the outlook is less good. […] Please bear in mind that CLL treatment is improving as doctors use new targeted drugs. These new treatments might improve the outlook for some people. […] Several factors can affect your outlook (prognosis). These are called prognostic factors. […] Some doctors use a scale called the Chronic Lymphocytic Leukaemia International Prognostic Index (CLL-IPI). This helps them talk to you about your prognosis.

• #77 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  Del (17p) which results in the loss of TP53, is the most important prognostic marker in CLL and is associated with poor outcomes, rapid disease progression and is historically associated with resistance to standard fludarabine-based chemoimmunotherapy. This chromosomal aberration is rare at diagnosis (less than 10%) but is more common in previously-treated patients. This underscores the importance of retesting for this aberration at clinical progression since it has therapeutic implications. 80% of patients with Del (17p) harbor mutations of the remaining TP53 allele. However, 4-5% of CLL patients carry a TP53 mutation in the absence of del (17p). These patients also carry a poor prognosis akin to patients with del (17p). This iterates to the fact that patients should undergo testing for TP53 mutation in addition to standard FISH testing for Del(17p). Patients with del(17p) or TP53 mutation respond well to targeted inhibitors of the B-cell receptor pathway and BCL-2 pathway, such as Ibrutinib and venetoclax respectively. Hence patients with these aberrations at diagnosis or progression are treated with these targeted inhibitors.

• #78 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  Del (17p) which results in the loss of TP53, is the most important prognostic marker in CLL and is associated with poor outcomes, rapid disease progression and is historically associated with resistance to standard fludarabine-based chemoimmunotherapy. This chromosomal aberration is rare at diagnosis (less than 10%) but is more common in previously-treated patients. This underscores the importance of retesting for this aberration at clinical progression since it has therapeutic implications. 80% of patients with Del (17p) harbor mutations of the remaining TP53 allele. However, 4-5% of CLL patients carry a TP53 mutation in the absence of del (17p). These patients also carry a poor prognosis akin to patients with del (17p). This iterates to the fact that patients should undergo testing for TP53 mutation in addition to standard FISH testing for Del(17p). Patients with del(17p) or TP53 mutation respond well to targeted inhibitors of the B-cell receptor pathway and BCL-2 pathway, such as Ibrutinib and venetoclax respectively. Hence patients with these aberrations at diagnosis or progression are treated with these targeted inhibitors.

• #79 The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

  https://www.mdpi.com/2075-4418/11/5/853

  In the era of targeted therapies, the mutations in BTK and PLCG2 have appeared in BCR-inhibitor refractory patients, as well as BCL2 mutations in venetoclax-resistant CLLs. […] The impressive progress achieved in all fields of CLL (diagnosis, prognosis and treatment) in the recent years goes hand-in-hand with the emergence of new challenges.

• #80 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  CD38 immunophenotype. CD38 positivity (30%) correlates with a worse prognosis, but there is a 30% false-positive rate and a 50% false-negative rate using IGH mutational status as the gold standard for prognosis. […] Other malignancies. Patients with CLL are also at increased risk of developing other malignancies, even before therapy. […] An international prognostic index for CLL (CLL-IPI) identified four prognostic subgroups based on IGH mutational status, clinical stage, age (65 years vs. 65 years), and TP53 status (no abnormalities vs. del(17p), TP53 variant, or both). […] Any new prognostic model, and even the commonly used CLL-IPI, may be outdated because of the use of highly effective frontline therapies, including BCL2 inhibitors and BTK inhibitors. Revalidation of these prognostic models will be required.

• #81 Survival statistics for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival/survival-statistics

  Survival statistics for cancer are very general estimates and must be interpreted very carefully. Because these statistics are based on the experience of groups of people, they cannot be used to predict a particular persons chances of survival. […] For chronic lymphocytic leukemia (CLL), survival can be estimated by as net survival. It can also be estimated as overall survival using the CLL International Prognostic Index (CLL-IPI). […] In Canada, the 5-year net survival for CLL is 86%. This means that, on average, about 86% of people diagnosed with CLL will live for at least 5 years. […] Overall survival is the percentage of people with a certain type of cancer who are expected to be alive at a specified period of time after their diagnosis. […] Only a doctor familiar with these factors can put all of this information together with survival statistics to arrive at a prognosis.

• #82 Survival statistics for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival/survival-statistics

  Survival statistics for cancer are very general estimates and must be interpreted very carefully. Because these statistics are based on the experience of groups of people, they cannot be used to predict a particular persons chances of survival. […] For chronic lymphocytic leukemia (CLL), survival can be estimated by as net survival. It can also be estimated as overall survival using the CLL International Prognostic Index (CLL-IPI). […] In Canada, the 5-year net survival for CLL is 86%. This means that, on average, about 86% of people diagnosed with CLL will live for at least 5 years. […] Overall survival is the percentage of people with a certain type of cancer who are expected to be alive at a specified period of time after their diagnosis. […] Only a doctor familiar with these factors can put all of this information together with survival statistics to arrive at a prognosis.

• #83 Chronic lymphocytic leukaemia (CLL) – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/chronic-lymphocytic-leukaemia/

  Chronic lymphocytic leukaemia (CLL) is a type of slow-growing leukaemia that affects developing B-lymphocytes. […] It is important to emphasise that for many people CLL remains stable for many months and years and has little, if any, impact on their lifestyle or general health. Around 30-50% of people diagnosed with CLL never require any treatment for their disease and can survive for many years despite their diagnosis. […] CLL usually develops slowly and progresses slowly, over months and years. Most people have no symptoms of their disease when first diagnosed. In these cases, people often require no treatment for a long time, apart from regular check-ups with their doctor to carefully monitor their health. Others may need to be treated soon after they are diagnosed.

• #84 Chronic lymphocytic leukaemia (CLL) – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/chronic-lymphocytic-leukaemia/

  Chronic lymphocytic leukaemia (CLL) is a type of slow-growing leukaemia that affects developing B-lymphocytes. […] It is important to emphasise that for many people CLL remains stable for many months and years and has little, if any, impact on their lifestyle or general health. Around 30-50% of people diagnosed with CLL never require any treatment for their disease and can survive for many years despite their diagnosis. […] CLL usually develops slowly and progresses slowly, over months and years. Most people have no symptoms of their disease when first diagnosed. In these cases, people often require no treatment for a long time, apart from regular check-ups with their doctor to carefully monitor their health. Others may need to be treated soon after they are diagnosed.

• #85 Survival statistics for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/prognosis-and-survival/survival-statistics

  Survival statistics for cancer are very general estimates and must be interpreted very carefully. Because these statistics are based on the experience of groups of people, they cannot be used to predict a particular persons chances of survival. […] For chronic lymphocytic leukemia (CLL), survival can be estimated by as net survival. It can also be estimated as overall survival using the CLL International Prognostic Index (CLL-IPI). […] In Canada, the 5-year net survival for CLL is 86%. This means that, on average, about 86% of people diagnosed with CLL will live for at least 5 years. […] Overall survival is the percentage of people with a certain type of cancer who are expected to be alive at a specified period of time after their diagnosis. […] Only a doctor familiar with these factors can put all of this information together with survival statistics to arrive at a prognosis.

• #86 The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

  https://www.mdpi.com/2075-4418/11/5/853

  In the era of targeted therapies, the mutations in BTK and PLCG2 have appeared in BCR-inhibitor refractory patients, as well as BCL2 mutations in venetoclax-resistant CLLs. […] The impressive progress achieved in all fields of CLL (diagnosis, prognosis and treatment) in the recent years goes hand-in-hand with the emergence of new challenges.

• #87 The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

  https://www.mdpi.com/2075-4418/11/5/853

  In the era of targeted therapies, the mutations in BTK and PLCG2 have appeared in BCR-inhibitor refractory patients, as well as BCL2 mutations in venetoclax-resistant CLLs. […] The impressive progress achieved in all fields of CLL (diagnosis, prognosis and treatment) in the recent years goes hand-in-hand with the emergence of new challenges.

• #88 Prognostic Factors in CLL – CLL Society

  https://cllsociety.org/2017/09/prognostic-factors-cll/

  In summary, the landscape of CLL therapeutics has changed drastically over the last few years. A huge reason for this is the identification of prognostic factors which throw more light into the heterogeneous biology of the disease. As a result, clinical trials are now being designed to test therapies in various subgroups of patients to predict disease progression, improve response and prolong patient survival.

• #89 Survival for chronic lymphocytic leukaemia | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/survival

  Chronic lymphocytic leukaemia (CLL) often develops very slowly. You might need little or no treatment. Although it is not usually curable, the disease can be under control for many years. But CLL can progress more quickly in some people. This might mean you need treatment earlier or need many different courses of treatment. […] The outlook (prognosis) can vary. Some people live for many years. But for some, the outlook is less good. […] Please bear in mind that CLL treatment is improving as doctors use new targeted drugs. These new treatments might improve the outlook for some people. […] Several factors can affect your outlook (prognosis). These are called prognostic factors. […] Some doctors use a scale called the Chronic Lymphocytic Leukaemia International Prognostic Index (CLL-IPI). This helps them talk to you about your prognosis.

• #90 Survival for chronic lymphocytic leukaemia | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/survival

  Although this prognostic index is quite recent, treatment continues to change. Doctors are using new targeted drugs to treat CLL. These might improve the outlook for some people. […] Doctors generally still think this index is a useful tool to help predict prognosis. […] Instead of survival by stage, we provide survival statistics from the Chronic Lymphocytic Leukaemia International Prognostic Index (CLL-IPI) study. […] Talk to your doctor about your prognosis. They might be able to tell you more about your risk group and your outlook. […] Please bear in mind that CLL treatment is improving as doctors use new targeted drugs. So people treated now might have a better outlook. […] Almost 95 out of 100 people (almost 95%) survive for 5 years or more after diagnosis. […] Around 80 out of 100 people (around 80%) survive for 5 years or more after diagnosis. […] Almost 65 out of 100 people (almost 65%) survive for 5 years or more after diagnosis. […] Almost 25 out of 100 people (almost 25%) survive for 5 years or more after diagnosis.

Zobacz więcej