Przewlekła białaczka szpikowa
Diagnostyka i diagnoza
Przewlekła białaczka szpikowa (CML) to nowotwór hematopoetyczny charakteryzujący się nadmierną proliferacją granulocytów w szpiku i krwi obwodowej. Diagnostyka opiera się na morfologii krwi obwodowej z rozmazem, biopsji szpiku kostnego oraz badaniach genetycznych, w tym wykrywaniu chromosomu Philadelphia (t(9;22)(q34;q11.2)) i genu fuzyjnego BCR-ABL1. Kluczowe metody to cytogenetyka, FISH oraz ilościowa PCR (qRT-PCR), umożliwiające wykrycie minimalnej choroby resztkowej. Diagnostyka pozwala na określenie fazy choroby (przewlekła, przyspieszona, blastyczna) oraz oceny ryzyka za pomocą wskaźników takich jak Sokal, Hasford czy EUTOS, co jest niezbędne do wyboru odpowiedniej terapii inhibitorami kinazy tyrozynowej (TKI). Monitorowanie odpowiedzi na leczenie obejmuje ocenę hematologiczną, cytogenetyczną i molekularną (MMR: redukcja transkryptu BCR-ABL1 o ≥3 log, ≤0,1% według skali międzynarodowej).
- Diagnostyka Przewlekłej Białaczki Szpikowej – wprowadzenie
- Wstępne podejrzenie CML – objawy i badania podstawowe
- Badania potwierdzające rozpoznanie CML
- Biopsja i aspiracja szpiku kostnego
- Badania cytogenetyczne i molekularne
- Badania obrazowe w diagnostyce CML
- Określenie fazy CML
- Faza przewlekła (chronic phase)
- Faza akceleracji (accelerated phase)
- Faza kryzy blastycznej (blast phase)
- Indeksy prognostyczne w CML
- Monitorowanie odpowiedzi na leczenie
- Diagnostyka oporności na leczenie
- Znaczenie prawidłowej diagnostyki dla procesu leczenia
- Wnioski końcowe
Diagnostyka Przewlekłej Białaczki Szpikowej – wprowadzenie
Przewlekła białaczka szpikowa (CML) to nowotwór krwi wywodzący się z komórek macierzystych szpiku kostnego. Charakteryzuje się nadmierną proliferacją dojrzewających granulocytów, które w postaci niedojrzałej i dojrzałej gromadzą się w szpiku kostnym i krwi obwodowej. Diagnostyka CML obejmuje szereg badań, które pozwalają na potwierdzenie obecności choroby i określenie jej fazy. Warto podkreślić, że u około 50% pacjentów choroba przebiega bezobjawowo i jest wykrywana przypadkowo podczas rutynowych badań krwi12.
Wstępne podejrzenie CML – objawy i badania podstawowe
Wstępne podejrzenie CML często pojawia się podczas rutynowych badań laboratoryjnych wykonywanych z innych przyczyn zdrowotnych lub podczas okresowych badań kontrolnych34. Pacjenci mogą zgłaszać niespecyficzne objawy takie jak: zmęczenie, gorączka, poty nocne, utrata masy ciała, czy uczucie pełności w lewym podżebrzu (spowodowane powiększeniem śledziony)56. Podstawowym badaniem inicjującym diagnostykę jest morfologia krwi obwodowej z rozmazem, która może wykazać charakterystyczne zmiany, takie jak:
- Podwyższona liczba leukocytów, często znacznie (leukocytoza)
- Obecność wszystkich form rozwojowych granulocytów obojętnochłonnych w rozmazie
- Zwiększona liczba bazofili i eozynofili
- Obniżona liczba erytrocytów
- Podwyższona lub obniżona liczba płytek krwi78
Badania potwierdzające rozpoznanie CML
Biopsja i aspiracja szpiku kostnego
Biopsja szpiku kostnego jest kluczowym badaniem w diagnostyce CML. Obejmuje ona dwa etapy, które zazwyczaj wykonywane są jednocześnie: aspirację szpiku (pobranie płynnej próbki) oraz biopsję (pobranie fragmentu tkanki kostnej zawierającej szpik). Procedurę wykonuje się najczęściej z tylnego grzebienia kości biodrowej po znieczuleniu miejscowym910.
Badanie szpiku kostnego pozwala na ocenę:
- Komórkowości szpiku (zwykle podwyższona w CML)
- Obecności i odsetka komórek blastycznych
- Stosunku poszczególnych linii komórkowych
- Obecności chromosomu Philadelphia lub genu fuzyjnego BCR-ABL111
Badania cytogenetyczne i molekularne
Badania genetyczne odgrywają kluczową rolę w diagnostyce CML. Do najważniejszych należą:
Analiza cytogenetyczna (kariotypowanie)
Badanie to pozwala na wykrycie chromosomu Philadelphia (Ph), który jest wynikiem translokacji pomiędzy chromosomami 9 i 22 – t(9;22)(q34;q11.2). Chromosom Ph jest obecny w komórkach szpiku kostnego u około 95% pacjentów z CML1213. Analiza wymaga hodowli komórek w laboratorium przez około tydzień, co wydłuża czas oczekiwania na wynik. Badanie to pozwala również na wykrycie dodatkowych aberracji chromosomowych, które mogą wskazywać na progresję choroby14.
Fluorescencyjna hybrydyzacja in situ (FISH)
FISH jest bardziej czułą metodą wykrywania chromosomu Philadelphia niż standardowe badania cytogenetyczne. Technika ta wykorzystuje fluorescencyjne sondy, które przyłączają się do określonych fragmentów chromosomów, pozwalając na wykrycie genu fuzyjnego BCR-ABL1. Badanie FISH może być wykonane z próbki krwi obwodowej lub szpiku kostnego i daje szybsze wyniki niż standardowa analiza cytogenetyczna1516.
Reakcja łańcuchowa polimerazy (PCR)
PCR, a szczególnie ilościowa reakcja łańcuchowa polimerazy z odwrotną transkryptazą (qRT-PCR), jest niezwykle czułą metodą wykrywania i ilościowego oznaczania genu fuzyjnego BCR-ABL1. Test ten może wykryć jedną komórkę CML na 100 000 komórek prawidłowych, co czyni go najbardziej czułym dostępnym badaniem. Jest to metoda preferowana do monitorowania odpowiedzi na leczenie, gdyż pozwala na wykrycie minimalnej choroby resztkowej171819.
Badania obrazowe w diagnostyce CML
Badania obrazowe nie są niezbędne do postawienia diagnozy CML, ale mogą być pomocne w ocenie rozmiaru śledziony oraz wykluczenia zajęcia innych narządów. Najczęściej wykonywane badania to:
- Badanie ultrasonograficzne jamy brzusznej – ocena wielkości śledziony i wątroby
- Tomografia komputerowa (CT) – w wybranych przypadkach do oceny zmian w narządach jamy brzusznej
- Rezonans magnetyczny (MRI) – rzadziej stosowany, głównie w przypadku podejrzenia zajęcia ośrodkowego układu nerwowego20
Określenie fazy CML
Na podstawie wyników badań diagnostycznych określa się fazę CML, co ma kluczowe znaczenie dla rokowania i wyboru metody leczenia. Wyróżnia się trzy fazy choroby:
Faza przewlekła (chronic phase)
Jest to najwcześniejsza i najłagodniejsza faza choroby, w której diagnozowanych jest ponad 90% pacjentów. Charakteryzuje się:
- Mniej niż 10% blastów w krwi obwodowej i szpiku kostnym
- Łagodnymi objawami lub ich brakiem
- Dobrą odpowiedzią na leczenie inhibitorami kinazy tyrozynowej (TKI)2122
Faza akceleracji (accelerated phase)
Faza ta charakteryzuje się:
- 10-19% blastów w krwi obwodowej lub szpiku kostnym
- Nasileniem objawów choroby
- Gorszą odpowiedzią na leczenie
- Możliwym pojawieniem się dodatkowych aberracji chromosomowych2324
Faza kryzy blastycznej (blast phase)
Jest to najbardziej zaawansowana faza choroby, przypominająca ostrą białaczkę. Charakteryzuje się:
- ≥20% blastów w krwi obwodowej lub szpiku kostnym
- Ciężkimi objawami klinicznymi
- Oporność na standardowe leczenie
- Niekorzystnym rokowaniem2526
Indeksy prognostyczne w CML
W CML stosuje się kilka systemów oceny ryzyka, które pomagają przewidzieć odpowiedź na leczenie i ryzyko progresji choroby. Najczęściej stosowane to:
- Wskaźnik Sokala – uwzględnia wiek pacjenta, rozmiar śledziony, liczbę płytek krwi i odsetek blastów we krwi obwodowej
- Wskaźnik Hasforda (Euro) – dodatkowo uwzględnia liczbę eozynofili i bazofili
- Wskaźnik EUTOS – uwzględnia odsetek bazofili i rozmiar śledziony2728
Wskaźniki te pozwalają na zakwalifikowanie pacjenta do grupy niskiego, pośredniego lub wysokiego ryzyka, co ma istotne znaczenie przy wyborze leczenia.
Monitorowanie odpowiedzi na leczenie
Diagnostyka CML nie kończy się na postawieniu rozpoznania, lecz obejmuje również monitorowanie odpowiedzi na leczenie. Wyróżnia się trzy rodzaje odpowiedzi:
Odpowiedź hematologiczna
Całkowita odpowiedź hematologiczna (CHR) oznacza normalizację parametrów morfologii krwi obwodowej i ustąpienie objawów klinicznych. Ocenia się ją na podstawie morfologii krwi obwodowej z rozmazem29.
Odpowiedź cytogenetyczna
Ocenia się ją na podstawie odsetka komórek Ph-pozytywnych w szpiku kostnym. Całkowita odpowiedź cytogenetyczna (CCyR) oznacza brak wykrywalnych komórek Ph-pozytywnych w badaniu cytogenetycznym3031.
Odpowiedź molekularna
Oceniana jest na podstawie poziomu transkryptu BCR-ABL1 mierzonego metodą qRT-PCR. Większa odpowiedź molekularna (MMR) oznacza redukcję poziomu transkryptu BCR-ABL1 o co najmniej 3 log (≤0,1% według skali międzynarodowej). Całkowita odpowiedź molekularna (CMR) oznacza brak wykrywalnego transkryptu BCR-ABL13233.
Monitorowanie odpowiedzi molekularnej powinno być wykonywane co 3 miesiące do osiągnięcia MMR, a następnie co 3-6 miesięcy34.
Diagnostyka oporności na leczenie
W przypadku nieosiągnięcia odpowiedzi na leczenie inhibitorami kinazy tyrozynowej lub utraty wcześniej uzyskanej odpowiedzi, konieczne jest przeprowadzenie dodatkowych badań diagnostycznych:
- Badanie mutacji domeny kinazy ABL1 – pozwala na identyfikację mutacji odpowiedzialnych za oporność na konkretne inhibitory kinazy tyrozynowej
- Powtórna analiza cytogenetyczna – w celu wykrycia ewentualnych dodatkowych aberracji chromosomowych
- Ocena przestrzegania zaleceń terapeutycznych przez pacjenta – nieprzyjmowanie leków zgodnie z zaleceniami może być przyczyną pozornej oporności3536
Znaczenie prawidłowej diagnostyki dla procesu leczenia
Prawidłowa i kompleksowa diagnostyka CML ma kluczowe znaczenie dla efektywnego leczenia pacjentów. Pozwala ona na:
- Potwierdzenie rozpoznania CML i wykluczenie innych chorób mieloproliferacyjnych
- Określenie fazy choroby i czynników prognostycznych
- Wybór optymalnego inhibitora kinazy tyrozynowej do leczenia pierwszej linii
- Monitorowanie skuteczności leczenia i wczesne wykrycie oporności
- Dostosowanie leczenia w przypadku niepowodzenia terapii pierwszej linii3738
Wnioski końcowe
Diagnostyka przewlekłej białaczki szpikowej obejmuje szereg badań – od morfologii krwi obwodowej, przez badanie szpiku kostnego, po zaawansowane analizy cytogenetyczne i molekularne. Kluczowym elementem diagnostyki jest wykrycie chromosomu Philadelphia lub genu fuzyjnego BCR-ABL1. Określenie fazy choroby i czynników prognostycznych pozwala na wybór optymalnej strategii leczenia. Regularne monitorowanie odpowiedzi na leczenie za pomocą badań molekularnych umożliwia wczesne wykrycie oporności i odpowiednią modyfikację terapii. Dzięki postępom w diagnostyce i leczeniu, CML stała się chorobą przewlekłą z dobrym rokowaniem dla większości pacjentów3940.
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Materiały źródłowe
- #1 Tests for Chronic Myeloid Leukemia | American Cancer Societyhttps://www.cancer.org/cancer/types/chronic-myeloid-leukemia/detection-diagnosis-staging/how-diagnosed.html
Many people with chronic myeloid leukemia (CML) don’t have symptoms when it’s diagnosed. The leukemia is often found when their doctor orders blood tests for an unrelated health problem or during a routine check-up. Even when symptoms are present, they’re often vague and non-specific. […] If signs and symptoms suggest you may have leukemia, the doctor will need to check your blood and bone marrow to be certain of this diagnosis. […] Most people with CML have too many white blood cells with a lot of early (immature) cells called myeloblasts or blasts. […] In people with CML, the bone marrow is often hypercellular because it’s full of leukemia cells. […] Some sort of gene testing will be done to look for the Philadelphia chromosome and/or the BCR-ABL gene. This type of test is used to confirm a CML diagnosis and learn more about your CML cells.
- #2 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
Many people with CML do not have symptoms when diagnosed. The most common sign of CML is an abnormal white blood cell count often found during blood tests for an unrelated health problem or during a routine checkup. To diagnose CML, doctors use a variety of tests to analyze blood and bone marrow cells. A pathologist, a doctor who specializes in identifying diseases by studying cells under a microscope, will examine the blood cells and the bone marrow cells. The samples should also be examined by a hematopathologist, a specialist who diagnoses diseases of the blood and marrow. […] […] Complete Blood Count (CBC) with Differential. This test is used to measure the number red blood cells, white blood cells and platelets in a sample of blood. It also measures the amount of hemoglobin in the red blood cells and the percentage of red blood cells in the sample. The CBC should include a differential. The differential measures the different types of white blood cells in the sample.
- #3 Chronic myelogenous leukemia – Symptoms and causes – Mayo Clinichttps://www.mayoclinic.org/diseases-conditions/chronic-myelogenous-leukemia/symptoms-causes/syc-20352417
Chronic myelogenous leukemia often doesn’t cause symptoms. It might be detected during a blood test. […] Make an appointment with your health care provider if you have any persistent symptoms that worry you. […] Most people with chronic myelogenous leukemia have a chromosome called the Philadelphia chromosome inside their blood cells. […] The Philadelphia chromosome forms when chromosome 9 and chromosome 22 break and exchange parts. This creates a short chromosome 22 and a new combination of instructions for the cells. […] Chronic myelogenous leukemia happens when something causes changes to the bone marrow cells. It’s not clear what starts this process. However, doctors have discovered how it progresses into chronic myelogenous leukemia. […] The extra-short chromosome 22 is called the Philadelphia chromosome. It is named for the city where it was discovered. The Philadelphia chromosome is present in the blood cells of 90% of people with chronic myelogenous leukemia.
- #4 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
Many people with CML do not have symptoms when diagnosed. The most common sign of CML is an abnormal white blood cell count often found during blood tests for an unrelated health problem or during a routine checkup. To diagnose CML, doctors use a variety of tests to analyze blood and bone marrow cells. A pathologist, a doctor who specializes in identifying diseases by studying cells under a microscope, will examine the blood cells and the bone marrow cells. The samples should also be examined by a hematopathologist, a specialist who diagnoses diseases of the blood and marrow. […] […] Complete Blood Count (CBC) with Differential. This test is used to measure the number red blood cells, white blood cells and platelets in a sample of blood. It also measures the amount of hemoglobin in the red blood cells and the percentage of red blood cells in the sample. The CBC should include a differential. The differential measures the different types of white blood cells in the sample.
- #5 Diagnosing Chronic Myelogenous Leukemia | NYU Langone Healthhttps://nyulangone.org/conditions/chronic-myelogenous-leukemia/diagnosis
Diagnosing Chronic Myelogenous Leukemia […] Specialists at NYU Langone are experienced at identifying all types of leukemia. Some are acute, or fast growing, and others are chronic, or slow growing. Chronic myelogenous leukemia, commonly known as CML, is a slow-growing cancer in which the bone marrowthe spongy tissue inside bones that contains stem cells, which make new blood cellsproduces too many immature white blood cells. […] Doctors may suspect you have CML if routine blood tests reveal elevated levels of both mature and immature white cells in the blood. Symptoms include fatigue, fever, and night sweats. Because leukemia can cause the spleenwhich fights infection and filters bloodto swell, some people may feel fullness below the ribs on the left side. However, some people have no symptoms.
- #6 Chronic Myeloid Leukemia (CML): Symptoms, Treatment & Prognosishttps://my.clevelandclinic.org/health/diseases/21845-chronic-myelogenous-leukemia-cml
Chronic myeloid leukemia (CML) is blood cancer that starts in the blood-forming myeloid cells or stem cells in your bone marrow. […] Healthcare providers may suspect you have CML if you have unusual blood test results. But they actually diagnose CML with chromosome or genetic tests that identify genetic changes or mutations. Common tests for CML include: […] Providers take small samples of fluid or tissue for genetic tests. A medical pathologist will perform tests to analyze abnormal cells genetic makeup. […] Healthcare providers typically treat chronic phase CML with tyrosine kinase inhibitors (TKIs). TKIs are a type of targeted therapy. In CML, the targets are the abnormal BCR-ABL enzymes that let abnormal white blood cells divide and multiply uncontrollably. […] If treatment puts chronic myeloid leukemia into remission, you wont have symptoms or signs of disease, but youll need medication to keep CML in remission. […] Right now, allogeneic stem cell transplantation is the only way to cure chronic myeloid leukemia. […] Overall, 90% of people with CML are alive five years after diagnosis.
- #7 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
People with CML often have: An increased white blood cell count, often a very high level; A decreased red blood cell count; A possible increase or decrease in the number of platelets, depending on the severity of the disease. […] […] Bone Marrow Aspiration and Biopsy. These tests are used to examine bone marrow cells to find abnormalities, and are generally done at the same time. The sample is usually taken from the patients hip bone after medicine has been given to numb the skin. For a bone marrow aspiration, a hollow needle is inserted through the hip bone and into the bone marrow to remove a liquid sample of cells. For a bone marrow biopsy, a wider needle is used to remove a small piece of bone that contains marrow. Both samples are examined under a microscope to look for chromosomal and other cell changes. […]
- #8 Diagnosing Chronic Myelogenous Leukemia | NYU Langone Healthhttps://nyulangone.org/conditions/chronic-myelogenous-leukemia/diagnosis
The different types of leukemia are treated differently, so its important to obtain the correct diagnosis. NYU Langone hematologistoncologists, who specialize in diagnosing blood cancers, perform several tests to identify leukemia, determine the type, and find out how advanced it is. […] During an initial exam, your oncologist draws blood to check the numbers of white cells, red cells, and platelets in it. In CML, white blood cell levels are often high and the platelet levels may be too high or too low. […] This blood test provides information about the number, type, and shape of blood cells. It can determine if immature white blood cells called myeloblasts are present alone, indicating AML, or if there is an increase of all stages of white blood cells, which are normally found in the bone marrow, in the blood. This is a sign of CML.
- #9 Chronic myelogenous leukemia – Diagnosis and treatment – Mayo Clinichttps://www.mayoclinic.org/diseases-conditions/chronic-myelogenous-leukemia/diagnosis-treatment/drc-20352422
A needle suctioning out liquid bone marrow from hipbone Bone marrow exam […] In a bone marrow aspiration, a healthcare professional uses a thin needle to remove a small amount of liquid bone marrow. It is usually taken from a spot in the back of the hip bone, also called the pelvis. A bone marrow biopsy is often done at the same time. This second procedure removes a small piece of bone tissue and the enclosed marrow. […] Tests and procedures used to diagnose chronic myelogenous leukemia include: […] Blood tests. A sample of blood is drawn using a needle. The sample is sent to a lab for a complete blood count, also called a CBC. A CBC checks the number of different types of cells in the blood. Chronic myelogenous leukemia often causes a very high number of white blood cells. Blood tests also can measure organ function to show if anything isn’t working properly.
- #10 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
People with CML often have: An increased white blood cell count, often a very high level; A decreased red blood cell count; A possible increase or decrease in the number of platelets, depending on the severity of the disease. […] […] Bone Marrow Aspiration and Biopsy. These tests are used to examine bone marrow cells to find abnormalities, and are generally done at the same time. The sample is usually taken from the patients hip bone after medicine has been given to numb the skin. For a bone marrow aspiration, a hollow needle is inserted through the hip bone and into the bone marrow to remove a liquid sample of cells. For a bone marrow biopsy, a wider needle is used to remove a small piece of bone that contains marrow. Both samples are examined under a microscope to look for chromosomal and other cell changes. […]
- #11 Diagnosing Chronic Myelogenous Leukemia | NYU Langone Healthhttps://nyulangone.org/conditions/chronic-myelogenous-leukemia/diagnosis
Leukemia starts in the bone marrow, so a doctor performs a bone marrow aspiration and biopsy to determine the type of leukemia a person has. During this procedure, which is done with a local anesthetic, your doctor uses two small needles to remove bone marrow fluid and tissue from the pelvic bone in the lower back. The cells are then sent to a laboratory for analysis by a hematopathologist, a doctor who specializes in diagnosing blood cancers. […] An analysis of cells collected during bone marrow aspiration, called karyotyping, can identify the BCR-ABL genetic mutation, also called the Philadelphia chromosome, which is present in most people with CML. […] A polymerase chain reaction test can detect the Philadelphia chromosome if a doctor isnt able to identify it via fluorescence in situ hybridization. In this analysis, small pieces of DNA are amplified making it easier for doctors to identify and measure irregularities in a small number of cells. This means that even small amounts of leukemia can be identified.
- #12 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
Cytogenetic Analysis. Cytogenetics is the study of chromosomes and chromosomal abnormalities. In these tests, special stains are applied to a bone marrow sample and then the cells are examined for chromosomal changes or abnormalities, such as the Philadelphia (Ph) chromosome. The presence of the Ph chromosome in the bone marrow cells, along with a high white blood cell count and other characteristic blood and bone marrow test findings, confirm the diagnosis of CML. In about 95 percent of people with CML, the Ph chromosome in bone marrow cells is detectable by cytogenetic analysis. In a small percentage of people with clinical signs of CML, the Ph chromosome cannot be detected by cytogenetic analysis. However, these patients almost always test positive for the BCR::ABL1 fusion gene on chromosome 22, found with the other types of tests, such as FISH and qPCR. […]
- #13 Chronic Myelogenous Leukemia (CML) Workup: Approach Considerations, Blood Count and Peripheral Smear, Bone Marrow Analysishttps://emedicine.medscape.com/article/199425-workup
The workup for chronic myelogenous leukemia (CML) consists of a complete blood count with differential, peripheral blood smear, and bone marrow analysis. […] The diagnosis of CML is based on the histopathologic findings in the peripheral blood and the Philadelphia (Ph1) chromosome in bone marrow cells. […] Findings from the workup in particular, the percentage of blasts in peripheral blood or bone marrow are used to determine the phase of CML: chronic, accelerated, or blast. […] Cytogenetic studies of the bone marrow cells, and even peripheral blood, should reveal the typical Ph1 chromosome, which is a reciprocal translocation of chromosomal material between chromosomes 9 and 22. […] This is the hallmark of CML, found in almost all patients with the disease and present throughout the entire clinical course of CML.
- #14 Chronic Myeloid Leukemia – CML | Choose the Right Testhttps://arupconsult.com/content/chronic-myelogenous-leukemia
Chromosome banding analysis is especially important because it detects other abnormalities, including additional copies of the Ph chromosome, isochromosome 17q, trisomy 8, and trisomy 19, which may indicate disease progression. […] RT-PCR testing should be performed along with chromosomal karyotyping at initial diagnosis for baseline BCR-ABL1 transcript identification and quantification. […] FISH testing may be used if chromosome banding analysis cannot be performed or if the breakpoint is cryptic and cannot be detected by chromosome banding analysis. […] Most cases of CML initially present in the chronic phase. Determining the CML phase is recommended at presentation because the phase will inform prognosis and treatment. […] CBC findings, such as the platelet count and percentage of blasts, are included in multiple CML risk scoring systems. Risk calculation is recommended if CML is diagnosed in the chronic phase. […] The results from standard hematology tests, cytogenetic tests, and molecular tests are used to assess the respective hematologic, cytogenetic, and molecular responses to tyrosine kinase inhibitor (TKI) therapy, and these test results may have prognostic significance.
- #15 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
Fluorescence In Situ Hybridization (FISH). This laboratory test is used to examine genes and chromosomes in cells. It is a slightly more sensitive method for detecting CML than the standard cytogenetic tests used to identify the Ph chromosome. FISH tests can identify the presence of the BCR::ABL1 gene. […] […] Quantitative Polymerase Chain Reaction (qPCR). The qPCR test is the most sensitive test used to detect and measure the quantity of the BCR::ABL1 gene in blood or bone marrow samples. It can detect very small amounts of the BCR::ABL1 gene, even when the Ph chromosome cannot be detected in blood or bone marrow cells with cytogenetic testing. It is capable of detecting one CML cell among 100,000 normal cells.
- #16 CML – Diagnosis | Sarah Cannonhttps://sarahcannon.com/for-patients/learn-about-cancer/blood-cancer/cml/diagnosis.dot
FISH is a sensitive test that can detect BCR-ABL by using fluorescent dyes. A standard cytogenetic analysis can detect the Ph chromosome in about 90 percent of CML patients. Some patients show no evidence of the Ph chromosome during basic cytogenetic testing, but the FISH test may detect the presence of the abnormal BCR-ABL gene. […] This test is used to diagnose CML and to track response to therapy once treatment has begun and can be performed with either blood or bone marrow cells. It is an extra-sensitive test that can detect and measure BCR-ABL oncogenes not found by other tests, such as FISH. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is needed. […] The phase of your chronic myeloid leukemia (CML) plays a large part in determining the type of treatment youâll receive. CML has three phases: chronic phase, accelerated phase and blast crisis phase.
- #17 Chronic Myeloid Leukemia (CML) | Diagnosing CML | LLShttps://www.lls.org/leukemia/chronic-myeloid-leukemia/diagnosis
Fluorescence In Situ Hybridization (FISH). This laboratory test is used to examine genes and chromosomes in cells. It is a slightly more sensitive method for detecting CML than the standard cytogenetic tests used to identify the Ph chromosome. FISH tests can identify the presence of the BCR::ABL1 gene. […] […] Quantitative Polymerase Chain Reaction (qPCR). The qPCR test is the most sensitive test used to detect and measure the quantity of the BCR::ABL1 gene in blood or bone marrow samples. It can detect very small amounts of the BCR::ABL1 gene, even when the Ph chromosome cannot be detected in blood or bone marrow cells with cytogenetic testing. It is capable of detecting one CML cell among 100,000 normal cells.
- #18 Tests for Chronic Myeloid Leukemia | American Cancer Societyhttps://www.cancer.org/cancer/types/chronic-myeloid-leukemia/detection-diagnosis-staging/how-diagnosed.html
Finding a Ph chromosome is helpful in diagnosing CML. […] PCR can be used to help diagnose CML. It’s also useful after treatment to see if copies of the BCR-ABL gene are still there. If copies of this gene are found it means that the leukemia is still present, even when the cells can’t be seen with a microscope.
- #19 Diagnosing Chronic Myelogenous Leukemia | NYU Langone Healthhttps://nyulangone.org/conditions/chronic-myelogenous-leukemia/diagnosis
A laboratory test called a quantitative reverse transcriptase polymerase chain can determine the amount of BCR-ABL in the blood. This test, performed with blood and bone marrow samples the doctor retrieved during aspiration, allows doctors to determine the cancers likelihood for responding to certain treatments.
- #20 Facts About CML | Fred Hutchinson Cancer Centerhttps://www.fredhutch.org/en/diseases/chronic-myeloid-leukemia/facts-resources.html
Diagnosing chronic myeloid leukemia (CML) involves blood and bone marrow tests, like a bone marrow biopsy. A biopsy shows if you have cancer. It will also give details about the type and subtype you have. […] At Fred Hutchinson Cancer Center, our hematopathologists will check and confirm your diagnosis. One thing they will look for is what phase your disease is in: the chronic phase, accelerated phase or blast phase. In each phase, CML behaves in a different way, and the treatment approach is different. […] To diagnose CML, figure out the phase of your disease, predict the outlook, plan your treatment and check how well treatment works, we will need to do blood and bone marrow tests and imaging tests. […] Blood and marrow tests show your levels of healthy blood cells and leukemia cells. They also give us details about your leukemia cells that affect your treatment plan. Imaging tests provide information about how CML is affecting your organs. […] A hematopathologist checks these samples for signs of cancer. Many of the same tests done on your blood can also be done on your marrow. […] Imaging tests that we use to check if CML is affecting your organs include: CT (computed tomography) scan, MRI (magnetic resonance imaging), Ultrasound.
- #21 Pathology Outlines – Chronic myeloid leukemia (CML), BCR::ABL1 positivehttps://www.pathologyoutlines.com/topic/myeloproliferativecml.html
Chronic myeloid leukemia (CML), BCR-ABL1 positive, is a myeloproliferative neoplasm (MPN) characterized by clonal granulocytic proliferation. […] Arises in a pluripotent stem cell with t(9;22)(q34.1;q11.2) chromosomal translocation and formation of the Philadelphia (Ph) chromosome, containing the BCR-ABL1 fusion gene. […] Most patients are diagnosed in the chronic phase. […] Almost 50% of patients diagnosed in the United States are asymptomatic and diagnosed during a routine examination. […] Chronic phase (CP): Leukocytosis (usually 12 – 1,000 x 10â¹/L, median: ~ 80 x 10â¹/L), < 2% blasts in blood, < 5% blasts in bone marrow, BCR-ABL1 positive by cytogenetics or molecular study. [...] Accelerated phase (AP) is defined by the presence of ⥠1 of the following criteria: 10 - 19% blasts in blood or marrow, persistent or increasing WBC > 10 x 10â¹/L, unresponsive to therapy.
- #22 CML – Diagnosis | Sarah Cannonhttps://sarahcannon.com/for-patients/learn-about-cancer/blood-cancer/cml/diagnosis.dot
FISH is a sensitive test that can detect BCR-ABL by using fluorescent dyes. A standard cytogenetic analysis can detect the Ph chromosome in about 90 percent of CML patients. Some patients show no evidence of the Ph chromosome during basic cytogenetic testing, but the FISH test may detect the presence of the abnormal BCR-ABL gene. […] This test is used to diagnose CML and to track response to therapy once treatment has begun and can be performed with either blood or bone marrow cells. It is an extra-sensitive test that can detect and measure BCR-ABL oncogenes not found by other tests, such as FISH. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is needed. […] The phase of your chronic myeloid leukemia (CML) plays a large part in determining the type of treatment youâll receive. CML has three phases: chronic phase, accelerated phase and blast crisis phase.
- #23 Pathology Outlines – Chronic myeloid leukemia (CML), BCR::ABL1 positivehttps://www.pathologyoutlines.com/topic/myeloproliferativecml.html
Blast phase (BP): ⥠20% blasts in marrow or blood or the presence of an extramedullary proliferation of blasts. […] Chronic phase: Leukocytosis with predominantly neutrophils and myelocytes, basophilia and eosinophilia, t(9;22)(q34;q11.2) by FISH, conventional cytogenetics or PCR. […] Most important prognostic indicator is response to tyrosine kinase inhibitors at the hematological, cytogenetic and molecular level. […] Chronic phase: tyrosine kinase inhibitor (TKI), acting by competitive inhibition at the ATP binding site of BCR-ABL1 oncoprotein. […] Tyrosine kinase inhibitor agents help achieve long term control of chronic myeloid leukemia in majority of patients. […] Hematopoietic stem cell transplant is reserved for those rare patients who present with blast phase, are resistant/intolerant to all tyrosine kinase inhibitors, or progress to accelerated or blast phase while on tyrosine kinase inhibitor therapy.
- #24 CML – Diagnosis | Sarah Cannonhttps://sarahcannon.com/for-patients/learn-about-cancer/blood-cancer/cml/diagnosis.dot
FISH is a sensitive test that can detect BCR-ABL by using fluorescent dyes. A standard cytogenetic analysis can detect the Ph chromosome in about 90 percent of CML patients. Some patients show no evidence of the Ph chromosome during basic cytogenetic testing, but the FISH test may detect the presence of the abnormal BCR-ABL gene. […] This test is used to diagnose CML and to track response to therapy once treatment has begun and can be performed with either blood or bone marrow cells. It is an extra-sensitive test that can detect and measure BCR-ABL oncogenes not found by other tests, such as FISH. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is needed. […] The phase of your chronic myeloid leukemia (CML) plays a large part in determining the type of treatment youâll receive. CML has three phases: chronic phase, accelerated phase and blast crisis phase.
- #25 Pathology Outlines – Chronic myeloid leukemia (CML), BCR::ABL1 positivehttps://www.pathologyoutlines.com/topic/myeloproliferativecml.html
Blast phase (BP): ⥠20% blasts in marrow or blood or the presence of an extramedullary proliferation of blasts. […] Chronic phase: Leukocytosis with predominantly neutrophils and myelocytes, basophilia and eosinophilia, t(9;22)(q34;q11.2) by FISH, conventional cytogenetics or PCR. […] Most important prognostic indicator is response to tyrosine kinase inhibitors at the hematological, cytogenetic and molecular level. […] Chronic phase: tyrosine kinase inhibitor (TKI), acting by competitive inhibition at the ATP binding site of BCR-ABL1 oncoprotein. […] Tyrosine kinase inhibitor agents help achieve long term control of chronic myeloid leukemia in majority of patients. […] Hematopoietic stem cell transplant is reserved for those rare patients who present with blast phase, are resistant/intolerant to all tyrosine kinase inhibitors, or progress to accelerated or blast phase while on tyrosine kinase inhibitor therapy.
- #26 CML – Diagnosis | Sarah Cannonhttps://sarahcannon.com/for-patients/learn-about-cancer/blood-cancer/cml/diagnosis.dot
Most patients are diagnosed during CML’s chronic phase when symptoms are mild or not noticeable. During this phase, your white cells can still fight infection and long-term drug therapy is used to control your CML. […] If youâre diagnosed during accelerated phase CML, you may have: A lower-than-normal number of red cells, A lower-than-normal number of platelets, An increase or decrease in white cells, A high number of blast cells in the blood and bone marrow, A swollen spleen, which can cause stomach discomfort, A general feeling of ill health. […] If youâre diagnosed in CML’s blast crisis phase, you usually have an increased number of blast cells in your bone marrow and blood. In addition, blast crisis phase patients also have a lower-than-normal number of red cells and platelets. […] Once CML reaches this more severe, advanced phase, its effects on patients are similar to those caused by an acute leukemia and can be life-threatening.
- #27 Diagnosis and Treatment of Chronic Myeloid Leukemia (CML) in 2015https://pmc.ncbi.nlm.nih.gov/articles/PMC5656269/
The prognosis of CP-CML has dramatically improved since the development of TKIs. […] Several prognostic scoring systems have been developed to assess the risk of poor outcome at presentation: the Sokal score and Hasford score were developed in the pre-imatinib era, but retain prognostic significance in imatinib-treated patients. […] Dynamic response assessment is essential to identify patients at high-risk of disease progression, who may benefit from a change of therapy. […] Response definitions are shown in table 1. A complete hematologic response (CHR) is defined by clinical and peripheral blood criteria. Cytogenetic response is classified according to the percentage of Ph-positive metaphases by routine karyotype on bone marrow aspiration. […] The European LeukemiaNet (ELN) 2013 guidelines place a strong emphasis on the importance of achieving MMR, ideally by the 12-month time-point.
- #28 Chronic Myeloid Leukemia: Evaluation and Diagnosis | MDedgehttps://blogs.the-hospitalist.org/content/chronic-myeloid-leukemia-evaluation-and-diagnosis
The most sensitive method for detecting BCR-ABL1 mRNA transcripts is the quantitative real-time PCR (RQ-PCR) assay, which is typically done on peripheral blood. […] This test should be done during the initial diagnostic workup in order to confirm the presence of BCR-ABL1 transcripts, and it is used as a standard method for monitoring response to TKI therapy. […] Calculating a patients Sokal score or EURO risk score at diagnosis remains an important component of the diagnostic workup in CP-CML, as this information has prognostic and therapeutic implications. […] The risk for disease progression to the accelerated or blast phases is higher in patients with intermediate- or high-risk scores compared to those with a low-risk score at diagnosis. […] After confirming a diagnosis of CML and selecting the most appropriate TKI for first-line therapy, the successful management of a CML patient relies on close monitoring and follow-up to ensure patients are meeting the desired treatment milestones.
- #29 Tests before and after diagnosis | Blood Cancer UKhttps://bloodcancer.org.uk/understanding-blood-cancer/leukaemia/chronic-myeloid-leukaemia-cml/cml-symptoms-testing/cml-testing/
The tests you have throughout your treatment for CML will measure how well the treatment is working. […] When your blood counts return to normal, youre said to have achieved a complete haematological response (CHR). […] This is another way of measuring how youve responded to the treatment youre on. […] If the tests cant detect the Philadelphia chromosome, or they show that your level of the BCR::ABL1 tyrosine kinase protein released by the new abnormal gene is less than 1%, you are said to have achieved a complete cytogenetic response (CCyR). […] The BCR::ABL1 or PCR test is a molecular test and is the best way to monitor levels of leukaemia in the blood. […] If you have less than 1 leukaemia cell in every 1000 blood cells (0.1%) this is known as a major molecular response (MMR). […] If no cancer cells at all can be detected in your PCR tests, you might hear your results referred to as undetectable transcripts. This is also sometimes called a complete molecular response (CMR).
- #30 Tests before and after diagnosis | Blood Cancer UKhttps://bloodcancer.org.uk/understanding-blood-cancer/leukaemia/chronic-myeloid-leukaemia-cml/cml-symptoms-testing/cml-testing/
The tests you have throughout your treatment for CML will measure how well the treatment is working. […] When your blood counts return to normal, youre said to have achieved a complete haematological response (CHR). […] This is another way of measuring how youve responded to the treatment youre on. […] If the tests cant detect the Philadelphia chromosome, or they show that your level of the BCR::ABL1 tyrosine kinase protein released by the new abnormal gene is less than 1%, you are said to have achieved a complete cytogenetic response (CCyR). […] The BCR::ABL1 or PCR test is a molecular test and is the best way to monitor levels of leukaemia in the blood. […] If you have less than 1 leukaemia cell in every 1000 blood cells (0.1%) this is known as a major molecular response (MMR). […] If no cancer cells at all can be detected in your PCR tests, you might hear your results referred to as undetectable transcripts. This is also sometimes called a complete molecular response (CMR).
- #31 Diagnosis and Treatment of Chronic Myeloid Leukemia (CML) in 2015https://pmc.ncbi.nlm.nih.gov/articles/PMC5656269/
The prognosis of CP-CML has dramatically improved since the development of TKIs. […] Several prognostic scoring systems have been developed to assess the risk of poor outcome at presentation: the Sokal score and Hasford score were developed in the pre-imatinib era, but retain prognostic significance in imatinib-treated patients. […] Dynamic response assessment is essential to identify patients at high-risk of disease progression, who may benefit from a change of therapy. […] Response definitions are shown in table 1. A complete hematologic response (CHR) is defined by clinical and peripheral blood criteria. Cytogenetic response is classified according to the percentage of Ph-positive metaphases by routine karyotype on bone marrow aspiration. […] The European LeukemiaNet (ELN) 2013 guidelines place a strong emphasis on the importance of achieving MMR, ideally by the 12-month time-point.
- #32 Tests before and after diagnosis | Blood Cancer UKhttps://bloodcancer.org.uk/understanding-blood-cancer/leukaemia/chronic-myeloid-leukaemia-cml/cml-symptoms-testing/cml-testing/
The tests you have throughout your treatment for CML will measure how well the treatment is working. […] When your blood counts return to normal, youre said to have achieved a complete haematological response (CHR). […] This is another way of measuring how youve responded to the treatment youre on. […] If the tests cant detect the Philadelphia chromosome, or they show that your level of the BCR::ABL1 tyrosine kinase protein released by the new abnormal gene is less than 1%, you are said to have achieved a complete cytogenetic response (CCyR). […] The BCR::ABL1 or PCR test is a molecular test and is the best way to monitor levels of leukaemia in the blood. […] If you have less than 1 leukaemia cell in every 1000 blood cells (0.1%) this is known as a major molecular response (MMR). […] If no cancer cells at all can be detected in your PCR tests, you might hear your results referred to as undetectable transcripts. This is also sometimes called a complete molecular response (CMR).
- #33 Diagnosis and Treatment of Chronic Myeloid Leukemia (CML) in 2015https://pmc.ncbi.nlm.nih.gov/articles/PMC5656269/
The prognosis of CP-CML has dramatically improved since the development of TKIs. […] Several prognostic scoring systems have been developed to assess the risk of poor outcome at presentation: the Sokal score and Hasford score were developed in the pre-imatinib era, but retain prognostic significance in imatinib-treated patients. […] Dynamic response assessment is essential to identify patients at high-risk of disease progression, who may benefit from a change of therapy. […] Response definitions are shown in table 1. A complete hematologic response (CHR) is defined by clinical and peripheral blood criteria. Cytogenetic response is classified according to the percentage of Ph-positive metaphases by routine karyotype on bone marrow aspiration. […] The European LeukemiaNet (ELN) 2013 guidelines place a strong emphasis on the importance of achieving MMR, ideally by the 12-month time-point.
- #34 Chronic Myeloid Leukemia: Evaluation and Diagnosis | MDedgehttps://blogs.the-hospitalist.org/content/chronic-myeloid-leukemia-evaluation-and-diagnosis
The NCCN and the ELN recommend monitoring RQ-PCR from the peripheral blood every 3 months in order to assess response to TKIs. […] Given the successful treatments available for patients with CML, it is crucial to identify patients with this disease, ensure they receive a complete, appropriate diagnostic workup including a bone marrow biopsy and aspiration with cytogenetic testing, and select the best therapy for each individual patient.
- #35 Diagnosis and Treatment of Chronic Myeloid Leukemia (CML) in 2015https://pmc.ncbi.nlm.nih.gov/articles/PMC5656269/
The key transcript levels at the 6, 12 and 18 month landmarks shown to be associated with favorable event-free survival (EFS) were 10%, 1% and 0.1%, respectively. […] Primary treatment failure can be defined as failure to achieve CHR/95% Ph+ at 3 months, 10% BCR-ABL/Ph35% at 6 months or 1% BCR-ABL/CCyR at 12 months. […] Identification of specific BCR-ABL1 mutations is critical to subsequent TKI choice.
- #36 Chronic Myeloid Leukemia: Laboratory Evaluation | Test Guide | Quest Diagnostics Chronic Myeloid Leukemia: Laboratory Evaluation Chronic Myeloid Leukemia: Laboratory Evaluationhttps://testdirectory.questdiagnostics.com/test/test-guides/TG_CML/chronic-myeloid-leukemia-laboratory-evaluation
When blood morphology findings suggest CML, the diagnosis is confirmed by identifying Ph using karyotyping and/or by detecting the BCR-ABL1 fusion gene with polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH) tests. Once CML is diagnosed, determining disease phases (chronic or blast phase) can help assess prognosis and select therapy. […] Laboratory tests that assess hematologic, cytogenetic, and molecular disease levels can be used to monitor response to TKI therapy. […] Laboratory tests that evaluate ABL1 kinase domain mutations may help guide treatment change when patients develop primary or secondary resistance to TKI therapy. ABL1 kinase domain mutation analysis is also recommended to help select initial treatment for patients with blast-phase CML. […] Table 2 provides an overview of the types of laboratory tests used for diagnosing CML and recognizing CML phases, determining prognosis, and monitoring treatment response.
- #37 Diagnosis | Stanford Health Carehttps://stanfordhealthcare.org/medical-conditions/cancer/chronic-myeloid-leukemia/patient-care-resources/diagnosis.html
If needed, you may undergo further imaging tests, blood work, or a biopsy. […] After this testing, it typically takes a few days to 2 weeks to review the results and confirm your diagnosis. Getting your test results can take time because your care team is working hard to determine an accurate diagnosis for you. […] Many health care professionals collaborate in the process and provide expert analysis, including your oncologist (cancer doctor), hematologist, and pathologist. […] Your care team will also determine the stage of your cancer. Staging describes the size of the cancer and whether (and how far) it has spread. Staging is the most important step in planning your treatment. […] Stanford chronic myeloid leukemia experts from several specialties meet as a team in weekly tumor boards. Based on the diagnosis, we determine our recommendations for the best sequence of treatment for each patient.
- #38 European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia | Leukemiahttps://www.nature.com/articles/s41375-023-02048-y
Cytogenetics along with FISH and/or RT-PCR should be used in all cases to confirm a diagnosis of CML. The limitations of each approach as standalone tests need to be understood and, where appropriate, included in clinical reports. […] BCR::ABL1 mRNA transcript type should be determined for all cases prior to treatment to enable appropriate follow up. […] The possibility of a rare BCR::ABL1 variant should be excluded. If testing for rare variants is not available, the diagnostic report should clearly state that the presence of a BCR::ABL1 remains a possibility and that further testing in an appropriate reference laboratory should be performed.
- #39 Chronic Myeloid Leukemia (CML): Symptoms, Treatment & Prognosishttps://my.clevelandclinic.org/health/diseases/21845-chronic-myelogenous-leukemia-cml
Chronic myeloid leukemia (CML) is blood cancer that starts in the blood-forming myeloid cells or stem cells in your bone marrow. […] Healthcare providers may suspect you have CML if you have unusual blood test results. But they actually diagnose CML with chromosome or genetic tests that identify genetic changes or mutations. Common tests for CML include: […] Providers take small samples of fluid or tissue for genetic tests. A medical pathologist will perform tests to analyze abnormal cells genetic makeup. […] Healthcare providers typically treat chronic phase CML with tyrosine kinase inhibitors (TKIs). TKIs are a type of targeted therapy. In CML, the targets are the abnormal BCR-ABL enzymes that let abnormal white blood cells divide and multiply uncontrollably. […] If treatment puts chronic myeloid leukemia into remission, you wont have symptoms or signs of disease, but youll need medication to keep CML in remission. […] Right now, allogeneic stem cell transplantation is the only way to cure chronic myeloid leukemia. […] Overall, 90% of people with CML are alive five years after diagnosis.
- #40 Chronic Myeloid Leukemia (CML) – Hematology and Oncology – Merck Manual Professional Editionhttps://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/chronic-myeloid-leukemia-cml
Chronic myeloid leukemia (CML) occurs when a pluripotent stem cell undergoes malignant transformation and clonal myeloproliferation, leading to a striking overproduction of mature and immature granulocytes. […] Peripheral blood smear, bone marrow aspirate, and demonstration of the Philadelphia chromosome are diagnostic. […] Chronic myeloid leukemia is most frequently suspected based on an abnormal CBC obtained incidentally or during evaluation of splenomegaly. […] Diagnosis is confirmed by finding the Ph chromosome in samples examined with cytogenetic or molecular studies. […] The peripheral smear (typically showing immature granulocytes, basophilia, and eosinophilia) helps distinguish CML from leukocytosis of other etiologies (eg, leukocytosis due to infection). […] Tyrosine kinase inhibitors are extremely effective, prolong survival, and may even be curative. […] Stem cell transplantation can be curative and may help patients who do not respond to tyrosine kinase inhibitors or who progress to accelerated or blast phase.