Materiały źródłowe

• #1 Molecular basis of β thalassemia and potential therapeutic targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5738298/

  The remarkable phenotypic diversity of thalassemia that range from severe anemia and transfusion-dependency, to a clinically asymptomatic state exemplifies how a spectrum of disease severity can be generated in single gene disorders. […] Identification of the genetic variants modifying fetal hemoglobin (HbF) production in combination with globin genotype provide some prediction of disease severity for thalassemia but generation of a personalized genetic risk score to inform prognosis and guide management requires a larger panel of genetic modifiers yet to be discovered. […] Clinical studies have shown that disease severity correlates well with the degree of imbalance between and normal globin chains and the size of the free chain pool. […] While the severity of beta thalassemia is primarily determined by the degree of beta chain deficiency, for any given beta thalassemia allele the severity of the disease can be alleviated by co-inheritance of thalassemia or by co-inheritance of factors that increase globin chain production and HbF levels. […] Using a combination of the HbF QTLs, the type of thalassemia mutations, and the globin genotype, a predictive score of severity has been proposed.

• #2 β-Thalassemia | Genetics in Medicine

  https://www.nature.com/articles/gim2016173

  -thalassemia is caused by reduced (+) or absent (0) synthesis of the -globin chains of hemoglobin. […] The clinical severity of -thalassemia syndromes is also influenced by genetic factors unlinked to globin genes as well as environmental conditions and management. Transfusions and oral iron chelation therapy have dramatically improved the quality of life for patients with thalassemia major. […] The prognosis has dramatically improved over the past decades with the advent of noninvasive methods to measure organ iron before the appearance of clinical symptoms, new chelators, and increased blood safety measures. […] After 2000, all of these developments led to a significant trend in decreasing cardiac mortality, which was previously reported to cause 71% of deaths for individuals with TM.

• #3 Thalassemia Intermedia: Chelator or Not?

  https://www.mdpi.com/1422-0067/23/17/10189

  Iron chelation therapy has been suggested to be given to NTDT patients aged ten years or older (or fifteen years or older in deletional HbH disease) that have liver iron concentration levels of 5 mg Fe/g or over dry weight (or serum ferritin level ≥ 800 ng/mL). Iron chelation therapy will only be given by showing that decreasing iron load leads to decreased morbidities or increased overall survival rate. […] After the introduction of iron chelation therapy in 1965, there was no longer an apparent difference in age of death in TM compared to TI patients. […] The survival of TM patients improved from poor adherence (regular transfusion and iron chelation therapy) of 15 to 25 years to good adherence, likely to at least 50 years. […] The hazard ratio of death in TM compared to TI patients decreased from 6.8 (CI 2.6–17.5) to 2.8 (CI 0.8–9.2) after the introduction of iron chelation therapy.

• #4 Molecular basis of β thalassemia and potential therapeutic targets

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5738298/

  The remarkable phenotypic diversity of thalassemia that range from severe anemia and transfusion-dependency, to a clinically asymptomatic state exemplifies how a spectrum of disease severity can be generated in single gene disorders. […] Identification of the genetic variants modifying fetal hemoglobin (HbF) production in combination with globin genotype provide some prediction of disease severity for thalassemia but generation of a personalized genetic risk score to inform prognosis and guide management requires a larger panel of genetic modifiers yet to be discovered. […] Clinical studies have shown that disease severity correlates well with the degree of imbalance between and normal globin chains and the size of the free chain pool. […] While the severity of beta thalassemia is primarily determined by the degree of beta chain deficiency, for any given beta thalassemia allele the severity of the disease can be alleviated by co-inheritance of thalassemia or by co-inheritance of factors that increase globin chain production and HbF levels. […] Using a combination of the HbF QTLs, the type of thalassemia mutations, and the globin genotype, a predictive score of severity has been proposed.

• #5 The survival rate of patients with beta-thalassemia major and intermedia and its trends in recent years in Iran

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6335498/

  The present study was conducted to determine the survival rate of patients with TM, TI, and sickle-thalassemia in highly endemic regions of Iran and to examine the effects of the main factors associated with survival in patients with TM and TI. […] The survival rate varied with the number of deaths in each age group, with the highest number of deaths occurring around age 45. The survival rate was calculated to be 0.92 in the 45-50 age group and as 0.75 in the 50-55 age group. […] The mean estimated survival of thalassemia patients in Iran (Tehran, Mazandaran, Bandar-e-Abbas [Hormozgan], Zahedan and Iranshahr) was calculated as 52.42 years using the Kaplan-Meier test (95% CI, 51.61 to 53.23). […] The rate of survival differed significantly between the patients with TM, TI, sickle, and unidentified thalassemia (p0.001). The patients with TI tended to survive the longest (55.59 years; 95% CI, 55.65 to 57.52), followed by the patients with sickle beta-thalassemia (53.00 years; 95% CI, 50.54 to 55.66), while the patients with TM died earlier (50.07 years; 95% CI, 48.54 to 51.60).

• #6 Predictive SNPs for β0-thalassemia/HbE disease severity | Scientific Reports

  https://www.nature.com/articles/s41598-021-89641-2

  Prediction of the disease severity is helpful for clinical management and quality of life of the patients. Knowing the severity of the affected child during pregnancy could aid in genetic counseling. […] This study explored the predictive SNPs for disease severity in 668 0-thalassemia/HbE patients. Analysis of SNP interaction revealed that rs766432 (BCL11A), rs9399137 (HBS1L-MYB) and rs72872548 (HBE1) are highest associated with clinical symptoms. […] The three predictive SNPs identified here are located in three loci that associated with HbF levels, which affect the central mechanism underlying disease pathophysiology, the degree of the excess of -globin chains and globin chain imbalance. […] The allele frequency of the predictive SNPs in this study of both Thai and Malaysian population are comparable. This suggested that the three SNPs can be used as predictive SNPs for disease severity at least for Southeast Asia where 0-thalassemia/HbE is prevalent. […] This study, to the best of our knowledge, is the first SNP risk score for prediction of clinical severity developed for a 0-thalassemia/HbE Southeast Asia population. This may assist in inform prognosis and guide therapeutics.

• #7 Predictive SNPs for β0-thalassemia/HbE disease severity | Scientific Reports

  https://www.nature.com/articles/s41598-021-89641-2

  -Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. […] The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian 0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia 0-thalassemia/HbE population. […] Discovery of genetic modifiers for 0-thalassemia/HbE provided a genetic basis for clinical application such as new targets for therapeutic intervention and predicting disease severity. […] The three predictive SNPs were validated in two independent cohorts of Thai and Malaysian patients with similar accuracy and specificity.

• #8 β-Thalassemia | Genetics in Medicine

  https://www.nature.com/articles/gim2016173

  Recent studies have shown that despite geographic differences, most individuals with transfusion-dependent thalassemia have normal cardiac iron; however, a significant proportion have simultaneous liver iron overload and the number of patients who die from liver disorders now exceeds that of individuals who die from cardiac diseases in some European countries. […] Even transfusion-independent patients with TI can develop hepatocarcinoma, which is mainly attributed to a state of iron overload in the liver. […] The clinical phenotype of homozygous -thalassemia may also be altered by the coinheritance of secondary genetic modifiers mapping outside HBB cluster and mainly influencing the complications of the thalassemia phenotype. […] Bone marrow transplantation (BMT) from an HLA-identical sibling, a widely applied alternative to traditional transfusion and chelation therapy, is the only available curative option for TM.

• #9 Predicting Factors of Survival Rates Among α-and β-Thalassemia Patients: A Retrospective 10-Year Data Analysis – TIF

  https://thalassaemia.org.cy/publications/scientific-literature/predicting-factors-of-survival-rates-among-%CE%B1-and-%CE%B2-thalassemia-patients-a-retrospective-10-year-data-analysis/

  Thalassemia genotype was a predictive factor of survival, and co-inheritance of the – and -thalassemia genotypes results in a shorter-term survival compared with other types, especially transfusion-dependent thalassemia. […] These results can be applied in clinical settings to predict and possibly extend the life expectancy of patients with thalassemia.

• #10 The survival rate of patients with beta-thalassemia major and intermedia and its trends in recent years in Iran

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6335498/

  Thalassemia is a common genetic disease in Iran, especially in the north and south of Iran. The present study sought to determine the survival rate of patients with thalassemia in highly endemic regions of Iran and its variation in patients born before and after 1971. […] The cumulative survival rate was calculated as 0.92, 0.83, 0.74, and 0.51 by ages 25, 35, 45, and 55, respectively. […] The present study showed relatively high survival rates in patients with thalassemia. The survival of patients was unfavorable in poorer regions (Zahedan and Iranshahr). Factors including women gender, a higher level of education, being married, and living in metropolises decreased the risk of death at younger ages and improved survival. […] Although the prognosis and survival of thalassemia patients are improving across the world and in Iran (based on results of some local studies), the prevalence of complications remains high in those affected, and cardiac disease remains the main cause of death in patients with high ferritin levels.

• #11 β-Thalassemia | Genetics in Medicine

  https://www.nature.com/articles/gim2016173

  In children who lack these risk factors, disease-free survival is more than 90%. […] The possibility of correction of the molecular defect in hematopoietic stem cells by transfer of a normal gene via a suitable vector or by homologous recombination is being actively investigated. […] Several clinical trials of gene therapy for -TM are ongoing in France, Italy, and the United States.

• #12 The survival rate of patients with beta-thalassemia major and intermedia and its trends in recent years in Iran

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6335498/

  The survival of thalassemia patients is affected by various factors, including gender, which was examined in the present study. […] The survival calculated in the life table and the Cox regression test showed that, in addition to men gender, having TM was associated with a higher risk of death compared to all other forms of the disease (HR, 4.22 for TM and 0.77 for TI). […] The risk of death was also 4.22 times higher in patients with TM than in those with the sickle form of the disease. A higher level of education, women gender, being married as opposed to being single, and living in metropolises (due to the better healthcare services) increased patient survival.

• #13 Thalassemia Intermedia: Chelator or Not?

  https://www.mdpi.com/1422-0067/23/17/10189

  The survival rates of regularly transfused patients were better than non-regularly transfused patients. […] Iron chelation therapy used in all regularly transfused patients and 67.7% of non-regularly transfused patients did not affect all-cause mortality nor mortality from cardiovascular disease but lowered the mortality rates from hepatic disease. […] Clear guidelines on initiation of chelation therapy for TI are unclear and based on data extrapolated from TM. […] Iron chelation therapy has been suggested to be the cornerstone of managing β-TI patients and is recommended in NTDT patients older than 10 years of age who have iron overload. Is there any strong evidence to support? Unfortunately, no studies showed iron chelation therapy did improve overall survival. We cannot be sure that iron chelation therapy did indeed increase survival of TI patients.

• #14 Beta Thalassemia: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/206490-overview

  Individuals with thalassemia minor (thalassemia trait) usually have mild, asymptomatic microcytic anemia. This state does not result in mortality or significant morbidity. […] The prognosis of patients with thalassemia major is highly dependent on the patient’s adherence to long-term treatment programs, namely the hypertransfusion program and lifelong iron chelation. Allogeneic bone marrow transplantation may be curative. […] The major causes of morbidity and mortality in beta thalassemia are anemia and iron overload. The severe anemia resulting from this disease, if untreated, can result in high-output cardiac failure; the intramedullary erythroid expansion may result in associated skeletal changes such as cortical bone thinning. The long-term increase in red-cell turnover causes hyperbilirubinemia and bilirubin-containing gallstones.

• #15 Alpha and Beta Thalassemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/0815/p339.html

  Persons with thalassemia trait have a normal life expectancy. […] Persons with beta thalassemia major live an average of 17 years and usually die by 30 years of age. Most deaths are caused by the cardiac complications of iron overload.

• #16 Thalassemia Intermedia: Chelator or Not?

  https://www.mdpi.com/1422-0067/23/17/10189

  Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes β-TI hemoglobin, E/β-thalassemia and hemoglobin H (HbH) disease. […] Questions are raised regarding the relationship between iron chelation therapy and decreased patient morbidity/mortality, as well as the starting threshold for chelation therapy. […] Intervention studies of iron chelation therapy included a subgroup of TI that required regular transfusion. Liver iron concentration (LIC) ≥ 5 mg/g/dw measured by MRI and ferritin level > 300 ng/mL were suggested as indicators to start iron chelation therapy, and iron chelation therapy was suggested to be stopped at a ferritin level ≤ 300 ng/mL. No studies showed improved overall survival rates by iron chelation therapy. TI morbidities and mortalities cannot be explained by iron overload alone.

• #17 Thalassemia: Types, Traits, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/14508-thalassemias

  A bone marrow transplant from a compatible sibling offers the best chance at a cure for thalassemia. Unfortunately, most people with thalassemia lack a suitable sibling donor. Also, a bone marrow transplant is a high-risk procedure that may result in severe complications, including death. […] You should expect a normal life expectancy if you have mild thalassemia. Even if your condition is moderate or severe, you have a good chance of long-term survival if you follow your treatment program (transfusions and iron chelation therapy). […] Heart disease from iron overload is the leading cause of death in people with thalassemia, so keeping up with your iron chelation therapy is extremely important.

• #18 Beta Thalassemia: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/206490-overview

  Increased iron deposition resulting from lifelong transfusions and enhanced iron absorption results in secondary iron overload. This overload causes clinical problems similar to those observed with primary hemochromatosis (eg, endocrine dysfunction, liver dysfunction, cardiac dysfunction). […] A broad spectrum of neurological complications has also been reported in beta thalassemia complications, although most were subclinical. These have included the following: cognitive impairment, abnormal findings on evoked potentials, cerebrovascular disease, peripheral neuropathy.

Zobacz więcej