Ostra białaczka szpikowa
Diagnostyka i diagnoza
Ostra białaczka szpikowa (AML) to agresywna choroba hematologiczna charakteryzująca się niekontrolowanym namnażaniem blastów szpikowych. Diagnostyka AML opiera się na ocenie klinicznej, morfologii krwi obwodowej (obecność blastów, niedokrwistość, małopłytkowość), badaniu szpiku kostnego (aspiracja i biopsja) z potwierdzeniem ≥20% blastów lub ≥10% w przypadku specyficznych aberracji genetycznych (np. t(8;21), inv(16), t(15;17)). Diagnostyka uzupełniona jest badaniami cytochemicznymi (barwienia na mieloperoksydazę, Sudan Black, nieswoistą esterazę), immunofenotypowaniem cytometrycznym oraz analizą cytogenetyczną (kariotyp, FISH) i molekularną (PCR, RT-PCR, NGS). Kluczowe mutacje genowe to m.in. NPM1, FLT3, CEBPA, RUNX1, które mają znaczenie prognostyczne i terapeutyczne. Klasyfikacja WHO (WHO-HAEM5, 2022) oraz Międzynarodowa Klasyfikacja Konsensualna (ICC) uwzględniają cechy morfologiczne i genetyczne, co umożliwia precyzyjną stratifikację pacjentów.
Diagnostyka ostrej białaczki szpikowej
Ostra białaczka szpikowa (AML) to agresywna, szybko postępująca choroba nowotworowa szpiku kostnego i krwi, charakteryzująca się niekontrolowanym namnażaniem niedojrzałych komórek blastycznych pochodzenia szpikowego. Dokładna i kompleksowa diagnostyka AML jest kluczowa dla postawienia prawidłowego rozpoznania, określenia podtypu choroby oraz zaplanowania odpowiedniego leczenia12.
Objawy i podejrzenie kliniczne
Proces diagnostyczny rozpoczyna się najczęściej od oceny objawów klinicznych pacjenta. Typowe objawy AML obejmują: zmęczenie, duszność, skłonność do siniaczeń lub krwawień, infekcje, ból kości, powiększone węzły chłonne, a czasem ból w klatce piersiowej i dyskomfort w jamie brzusznej związany z powiększoną śledzioną lub wątrobą12. W trakcie badania fizykalnego lekarz zwraca szczególną uwagę na obecność siniaków, krwawień z jamy ustnej lub dziąseł, objawów infekcji oraz powiększenie węzłów chłonnych, wątroby i śledziony1.
Badania krwi
Podstawowym badaniem diagnostycznym jest morfologia krwi obwodowej z rozmazem12. W przypadku AML badanie to może wykazać:
- Zwiększoną liczbę niedojrzałych białych krwinek (blastów) lub zmniejszoną ogólną liczbę białych krwinek1
- Niedokrwistość (obniżony poziom hemoglobiny i liczby czerwonych krwinek)11
- Małopłytkowość (zmniejszoną liczbę płytek krwi)11
Obecność blastów w krwi obwodowej jest istotnym wskaźnikiem możliwej AML, ale ich brak nie wyklucza choroby, gdyż komórki białaczkowe mogą być ograniczone do szpiku kostnego1.
Badanie szpiku kostnego
Kluczowym elementem diagnostyki AML jest badanie szpiku kostnego12. Procedura obejmuje dwa elementy:
- Aspiracja szpiku kostnego – pobranie płynnej próbki szpiku kostnego za pomocą igły, najczęściej z kości biodrowej11
- Biopsja szpiku kostnego – pobranie niewielkiej ilości litej tkanki szpikowej do badania11
Badanie szpiku kostnego przeprowadzane jest zwykle w znieczuleniu miejscowym, czasem z zastosowaniem sedacji. Aspiration i biopsja wykonywane są zwykle podczas jednej procedury1.
Do rozpoznania AML wymagane jest stwierdzenie co najmniej 20% blastów w szpiku kostnym lub krwi obwodowej21. Wyjątkiem są przypadki z określonymi zmianami genetycznymi (np. t(8;21), inv(16) lub t(16;16), t(15;17)), gdzie rozpoznanie AML można postawić nawet przy niższym odsetku blastów (co najmniej 10%)11.
Badania cytochemiczne
Badania cytochemiczne polegają na barwieniu komórek szpiku kostnego i krwi obwodowej specjalnymi barwnikami, co pomaga odróżnić AML od ostrej białaczki limfoblastycznej (ALL) oraz określić podtyp AML1. Najczęściej stosowane barwienia to:
- Barwienie na mieloperoksydazę lub Sudan Black – pomocne w identyfikacji AML i odróżnieniu jej od ALL2
- Barwienie na nieswoistą esterazę – pomocne w identyfikacji komponentu monocytowego w AML3
Obecność pałeczek Auera (specyficznych wtrętów w komórkach) podczas badania mikroskopowego silnie sugeruje rozpoznanie AML11.
Zaawansowane metody diagnostyczne
Immunofenotypowanie
Immunofenotypowanie metodą cytometrii przepływowej jest niezbędnym narzędziem w diagnostyce AML21. Technika ta pozwala na identyfikację specyficznych antygenów (markerów) na powierzchni komórek białaczkowych, co pomaga:
- Potwierdzić rozpoznanie AML1
- Odróżnić AML od innych typów białaczek1
- Określić podtyp AML1
- Identyfikować aberracje immunofenotypowe charakterystyczne dla komórek białaczkowych1
Immunofenotypowanie dostarcza informacji o linii pochodzenia komórek białaczkowych i ich stopniu dojrzałości, co jest kluczowe dla prawidłowej klasyfikacji choroby1.
Badania cytogenetyczne
Analiza cytogenetyczna stanowi istotny element diagnostyki AML, dostarczając ważnych informacji prognostycznych i pomagając w klasyfikacji choroby11. Podstawowe techniki cytogenetyczne obejmują:
- Klasyczna analiza kariotypu – badanie chromosomów w komórkach dzielących się (metafaza), pozwalające na identyfikację dużych zmian chromosomowych2
- Fluorescencyjna hybrydyzacja in situ (FISH) – technika wykorzystująca fluorescencyjne sondy do wykrywania specyficznych zmian chromosomowych, często niewidocznych w klasycznej analizie kariotypu31
Do najczęściej obserwowanych zmian cytogenetycznych w AML należą: t(15;17), trisomia 8, t(8;21), inv(16) lub t(16;16) oraz rearanżacje 11q23.31.
Badania molekularne
Badania molekularne stanowią obecnie nieodłączny element diagnostyki AML, dostarczając informacji o zmianach genetycznych na poziomie DNA1. Najczęściej stosowane techniki to:
- Reakcja łańcuchowa polimerazy (PCR) – bardzo czuła metoda pozwalająca na wykrycie nawet niewielkich ilości komórek białaczkowych w próbce1
- Odwrotna transkrypcja PCR (RT-PCR) – umożliwia wykrycie specyficznych translokacji genowych i fuzji genów1
- Sekwencjonowanie nowej generacji (NGS) – pozwala na kompleksową analizę wielu genów jednocześnie, identyfikując mutacje mające znaczenie diagnostyczne i prognostyczne21
Kluczowe mutacje genów badane w AML obejmują m.in. mutacje w genach NPM1, FLT3, CEBPA, RUNX1, które mają istotne znaczenie dla prognozy i wyboru terapii1.
Klasyfikacja i podtypy AML
Klasyfikacja WHO
Aktualnie najczęściej stosowanym systemem klasyfikacji AML jest klasyfikacja Światowej Organizacji Zdrowia (WHO), która uwzględnia zarówno cechy morfologiczne, jak i genetyczne komórek białaczkowych1. System ten regularnie aktualizowany, a jego najnowsza wersja opublikowana została w 2022 roku (WHO-HAEM5)1.
Klasyfikacja WHO identyfikuje poszczególne podtypy AML na podstawie charakterystycznych zmian genetycznych, co ma kluczowe znaczenie prognostyczne i terapeutyczne2.
Klasyfikacja ICC
Międzynarodowa Klasyfikacja Konsensualna (ICC) jest alternatywnym systemem klasyfikacji AML, również opartym głównie na zmianach genetycznych w komórkach białaczkowych2.
Podtypy AML wg French-American-British (FAB)
Historyczna klasyfikacja FAB dzieli AML na osiem podtypów (od M0 do M7) na podstawie wyglądu komórek białaczkowych pod mikroskopem oraz stopnia ich dojrzałości11.
Badania dodatkowe
Badanie płynu mózgowo-rdzeniowego
Nakłucie lędźwiowe (punkcja lędźwiowa) może być przeprowadzone w celu wykluczenia zajęcia ośrodkowego układu nerwowego przez białaczkę, szczególnie u pacjentów z objawami neurologicznymi11. Badanie to polega na pobraniu próbki płynu mózgowo-rdzeniowego do analizy1.
Badania obrazowe
Badania obrazowe mają ograniczone zastosowanie w diagnostyce AML, ale mogą być przydatne do oceny powikłań choroby lub efektów zajęcia narządów pozaszpikowych1. Najczęściej stosowane badania obrazowe to:
- Tomografia komputerowa (CT) lub rezonans magnetyczny (MRI) mózgu – w przypadku podejrzenia zajęcia ośrodkowego układu nerwowego1
- Badanie rentgenowskie klatki piersiowej – w poszukiwaniu infekcji lub innych powikłań2
- Ultrasonografia jamy brzusznej – w celu oceny powiększenia wątroby, śledziony lub węzłów chłonnych2
- Echokardiografia – do oceny funkcji serca przed rozpoczęciem chemioterapii2
Badania biochemiczne
Badania biochemiczne krwi wykonywane są w celu oceny ogólnego stanu zdrowia pacjenta i funkcji narządów wewnętrznych1. Typowe badania obejmują:
- Ocenę funkcji nerek i wątroby1
- Poziom elektrolitów1
- Poziom kwasu moczowego1
- Poziom dehydrogenazy mleczanowej (LDH)11
- Badania układu krzepnięcia1
Ocena rokownicza
Czynniki prognostyczne
Na podstawie wyników badań diagnostycznych określane są czynniki prognostyczne, które pomagają przewidzieć odpowiedź na leczenie i rokowanie pacjenta1. Najważniejsze czynniki prognostyczne obejmują:
- Zmiany cytogenetyczne – określone anomalie chromosomalne mogą być związane z lepszym lub gorszym rokowaniem11
- Mutacje genowe – obecność określonych mutacji genowych może wpływać na rokowanie2
- Wiek pacjenta – młodszy wiek zwykle wiąże się z lepszym rokowaniem1
- Stan ogólny pacjenta1
- Odpowiedź na leczenie indukujące3
Stratyfikacja ryzyka
Na podstawie czynników prognostycznych pacjenci z AML klasyfikowani są do grup ryzyka, co pomaga w doborze odpowiedniej intensywności leczenia2. Najczęściej stosowany system stratyfikacji ryzyka został opracowany przez European LeukemiaNet (ELN)1.
Choroba resztkowa
Monitorowanie minimalnej choroby resztkowej
Ocena minimalnej choroby resztkowej (MRD) polega na wykrywaniu niewielkich ilości komórek białaczkowych pozostających po leczeniu, niewidocznych w standardowych badaniach1. Metody oceny MRD obejmują:
Monitorowanie MRD jest przydatne w ocenie odpowiedzi na leczenie, prognozowaniu ryzyka nawrotu oraz podejmowaniu decyzji terapeutycznych11.
Remisja i odpowiedź na leczenie
Kryteria remisji w AML obejmują3:
- Mniej niż 5% blastów w szpiku kostnym21
- Prawidłową morfologię krwi obwodowej2
- Brak objawów białaczki w ośrodkowym układzie nerwowym lub innych narządach2
Ocena odpowiedzi na leczenie obejmuje regularne badania krwi i szpiku kostnego1.
Zintegrowane podejście diagnostyczne
Współczesna diagnostyka AML wymaga zintegrowanego podejścia łączącego różne metody diagnostyczne1. Kompleksowa ocena obejmująca cytomorfologię, cytochemię, immunofenotypowanie, cytogenetykę i badania molekularne pozwala na pełną charakterystykę choroby, co jest niezbędne do optymalizacji leczenia11.
Postęp w dziedzinie diagnostyki molekularnej, szczególnie w zakresie sekwencjonowania nowej generacji, umożliwia coraz bardziej precyzyjną diagnostykę i personalizację terapii11.
Multidyscyplinarne zespoły diagnostyczne
Ze względu na złożoność diagnostyki AML, optymalnym podejściem jest współpraca multidyscyplinarnego zespołu specjalistów obejmującego hematologów, hematopatologów, genetyków i specjalistów medycyny laboratoryjnej12.
Szybka diagnostyka
Ze względu na agresywny charakter AML, proces diagnostyczny powinien być przeprowadzony jak najszybciej, a leczenie powinno być rozpoczęte niezwłocznie po postawieniu rozpoznania11. Opóźnienie w diagnostyce i leczeniu może negatywnie wpłynąć na rokowanie pacjenta1.
W niektórych przypadkach, szczególnie przy podejrzeniu ostrej białaczki promielocytowej (APL), specjalnego podtypu AML charakteryzującego się translokacją t(15;17), badania diagnostyczne i rozpoczęcie leczenia powinny być przeprowadzone w trybie pilnym ze względu na wysokie ryzyko powikłań krwotocznych11.
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Materiały źródłowe
- #1 Tests for Acute Myeloid Leukemia (AML) | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-diagnosed.html
Certain signs and symptoms might suggest that a person could have acute myeloid leukemia (AML), but tests are needed to confirm the diagnosis. […] Different tests can be used to help diagnose AML. If AML is found, tests will be done to learn more about it, including the subtype of AML. […] If the doctor thinks you might have leukemia, tests will be done on samples of cells from your blood and bone marrow (the inner parts of some bones, where new blood cells are made). […] Blood tests are generally the first tests done to look for leukemia. […] Checking the bone marrow for leukemia cells is a key part of testing for it. […] These bone marrow tests are used to help diagnose leukemia, but they might also be repeated later to see how well the leukemia is responding to treatment. […] One or more of the following lab tests may be done on the samples to diagnose AML, to determine the specific subtype of AML, and to learn more about the leukemia.
- #1 Acute myelogenous leukemia – Diagnosis and treatment – Mayo Clinichttps://www.mayoclinic.org/diseases-conditions/acute-myelogenous-leukemia/diagnosis-treatment/drc-20369115
Acute myeloid leukemia diagnosis often begins with an exam that checks for bruising, bleeding in the mouth or gums, infection, and swollen lymph nodes. Other tests include blood and lab tests, bone marrow biopsy, lumbar puncture, and imaging. […] Blood tests for acute myelogenous leukemia might include a test to count the number of blood cells in a sample of blood. This test is called a complete blood count. The results may show too many or too few white blood cells. Often the test finds that there are not enough red blood cells and not enough platelets. Another blood test looks for immature white blood cells called myeloblasts in the blood. These cells typically aren’t found in the blood. But they can occur in the blood of people with AML. […] Bone marrow aspiration and biopsy are procedures that involve collecting cells from the bone marrow. In bone marrow aspiration, a needle is used to draw a sample of the bone marrow fluid. In a bone marrow biopsy, a needle is used to collect a small amount of solid tissue. The samples are typically taken from the hip bone. The samples go to a lab for testing.
- #1https://www.nhs.uk/conditions/acute-myeloid-leukaemia/diagnosis/
In the initial stages of diagnosing acute myeloid leukaemia (AML), your GP will check for physical signs of the condition and arrange for you to have blood tests. A high number of abnormal white blood cells, or a very low blood count in the test sample, could indicate leukaemia. If this is the case, you’ll be urgently referred to a a specialist in treating blood conditions (haematologist). A haematologist may carry out further tests. To confirm a diagnosis of AML, a small sample of your bone marrow will be taken to examine under a microscope. This procedure is known as a bone marrow biopsy. The bone marrow sample will be checked for cancerous cells. If cancerous cells are present, the biopsy can also be used to determine the type of leukaemia you have. Other tests can be used to get more information about the progress and extent of your AML. They can also help decide how it should be treated. Genetic tests can be carried out on blood and bone marrow samples to find out what type of AML you have. This can help doctors make decisions about the most appropriate treatment. In rare situations where it’s thought there’s a risk that AML has spread to your nervous system, a lumbar puncture may be carried out. If cancerous cells are found in your nervous system, it may affect your treatment.
- #1 Tests for Acute Myeloid Leukaemia (AML) | Cancer Council NSWhttps://www.cancercouncil.com.au/acute-myeloid-leukaemia/diagnosis/tests/
A combination of blood and bone marrow tests will help your doctor confirm the diagnosis and work out the subtype of acute myeloid leukaemia (AML) you have. […] Your doctor will take a sample of blood and send it to a laboratory for a full blood count (FBC). This will show whether leukaemia cells are present and whether the levels of the different types of blood cells are different from what would be expected in a healthy person. […] Blood cells develop in your bone marrow, so your doctor will check your bone marrow for signs of leukaemia. […] The bone marrow samples are sent to a laboratory where they will be tested to work out the subtype of AML and any gene changes that may have occurred. […] This test looks for certain markers that are on the surface of leukaemia cells. Looking at the patterns of these markers can help your doctor confirm that the leukaemia is AML (and not ALL) and to work out the subtype.
- #1 Azthena logo with the word Azthenahttps://www.news-medical.net/health/Acute-Myeloid-Leukemia-Diagnosis.aspx
If a patients presents with the symptoms of acute myeloid leukemia a battery of tests are ordered. The tests used to diagnose AML include the following. […] First a complete blood count is prescribed. Anemia is commonly detected with haemoglobin levels usually less than 5g/dl. In addition there is thrombocytopenia of varying degrees. This means there is a low platelet count. […] White blood cell (WBC) count is usually high but may be normal or low. The number of neutrophils is usually low. […] When a small sample of blood is smeared onto a glass slide and examined under the microscope there may be presence of blast cells. This is called peripheral blood smear. The blood smear may be normal if the blast cells are confined to the bone marrow. […] The percentage of cells in the bone marrow or blood that are blasts is particularly important. Having at least 20% blasts in the marrow or blood is generally required for a diagnosis of AML. It can also be diagnosed if the blasts have a chromosome change that can be seen in specific types of AML even if the blast percentage does not reach 20%.
- #1 Acute myeloid leukemia diagnosis – Leukaemia Foundationhttps://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/acute-myeloid-leukaemia/diagnosis/
Acute myeloid leukaemia diagnosis […] How is AML diagnosed? […] AML is diagnosed by examining samples of your blood and bone marrow in a variety of tests. […] The first step in the diagnosis is a simple blood test called a full blood count (FBC) or complete blood count (CBC). This involves a sample of blood from a vein in your arm being sent to the laboratory for investigation. Many of the white blood cells may be abnormal leukaemic blast cells and the presence of these blast cells suggests you have AML. […] If the results of your blood tests suggest that you might have AML, a bone marrow biopsy may be required to help confirm the diagnosis. A bone marrow biopsy involves taking a sample of bone marrow, usually from the back of the hip bone, and sending it to the laboratory for examination under the microscope. The bone marrow biopsy may be done in the haematologistâs rooms, a clinic or a day procedure centre and it is usually performed under local anaesthesia with sedation given either by tablet or through a small drip in your arm. The sample of bone marrow is examined in the laboratory to determine the number and type of cells present and the amount of haemopoiesis (blood forming) activity taking place there. The diagnosis of AML is confirmed by the presence of an excessive number of blast cells in the bone marrow.
- #1 Acute myeloid leukemia – Wikipediahttps://en.wikipedia.org/wiki/Acute_myeloid_leukemia
Acute myeloid leukemia […] Diagnosis is generally based on bone marrow aspiration and specific blood tests. […] A definitive diagnosis requires a bone marrow aspiration and biopsy. […] Bone marrow is examined under light microscopy, as well as flow cytometry, to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. acute lymphoblastic leukemia), and to provide information about how mature or immature the affected cells are that can assist in classifying the subtype of disease. […] The standard classification scheme for AML is the World Health Organization (WHO) system. […] According to the WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts, except in three forms of acute myeloid leukemia with recurrent genetic abnormalities: t(8;21), inv(16) or t(16;16), and acute promyelocytic leukemia with PML-RARA, in which the presence of the genetic abnormality is diagnostic irrespective of blast percent.
- #1 How AML Subtypes Affect Outlook & Treatment | American Cancer Society | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html
In both systems, the percentage of blasts (very immature blood cells) in the bone marrow or blood is important in diagnosing AML. […] If the AML cells have certain gene or chromosome changes (see below), usually at least 10% of the cells in the bone marrow or blood must be blasts. […] If there are no major gene or chromosome changes in the AML cells, usually at least 20% of the cells in the bone marrow or blood must be blasts to diagnose AML. […] The classification of AML has become more complex over time, as doctors have learned more about the genetic changes inside AML cells. […] The International Consensus Classification (ICC) can also be used to determine the AML subtype. […] Like the WHO classification, its based mainly on the gene or chromosome changes in the AML cells, but other factors can be important, too.
- #1 Acute Myeloid Leukemia (AML) Differential Diagnoseshttps://emedicine.medscape.com/article/197802-differential
Traditionally, most acute myeloid leukemia (AML) subtypes have been distinguished from myelodysplastic syndrome (MDS) by the presence of at least 20% blasts in the bone marrow or peripheral blood, and for that reason, patients with blast levels that are elevated but less than 20% would typically be ineligible for participation in AML clinical trials. […] However, current classification recognizes MDS/AML in patients with 10-19% blasts. […] Regardless of the blast percentage, patients are considered to have AML if they have the clonal, recurring cytogenetic abnormalities t(8;21)(q22;q22), inv(16)(p13q22), or t(16;16)(p13;q22). […] Failure to rapidly distinguish a patient with AML from a patient with a less urgent hematologic disorder is the most important medicolegal pitfall in this setting.
- #1 Acute myeloid leukemia – Wikipediahttps://en.wikipedia.org/wiki/Acute_myeloid_leukemia
The basis of allogenic stem cell transplantation is on a graft versus leukemia effect whereby graft cells stimulate an immune response against leukemia cells. […] Target therapy is a type of treatment that uses drugs or other substances to target specific molecules that cancer cells need to survive and spread. […] A complete blood count, which is a blood test, is one of the initial steps in the diagnosis of AML. […] A blood film may show leukemic blast cells. […] Inclusions within the cells called Auer rods, when seen, make the diagnosis highly likely. […] Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. […] The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. […] The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. […] The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.
- #1 Toward Integrated Genomic Diagnosis in Routine Diagnostic Pathology by the World Health Organization Classification of Acute Myeloid Leukemiahttps://www.scientificarchives.com/article/toward-integrated-genomic-diagnosis-in-routine-diagnostic-pathology-by-the-world-health-organization-classification-of-acute-myeloid-leukemia
The identification of even rare but unequivocal Auer rods by morphologic review, although that may require time, confirms the diagnosis of a myeloid neoplasm. […] For routine integrated genomics diagnosis, the WHO classification is meant to be applied worldwide, including in countries with limited resources or advanced molecular genetic techniques. […] All of the above advances now increasingly necessitate comprehensive, integrated diagnostics, including genomics for AML diagnosis, prognosis, and therapy. […] The WHO2016/2017 classification of AML represents a significant milestone for the care of patients with AML and has paved the way for future continued collaboration and innovation toward further progress for patient care.
- #1 The power and potential of integrated diagnostics in acute myeloid leukaemiahttps://pmc.ncbi.nlm.nih.gov/articles/PMC6973013/
The presence and expression strength of antigens constitute the immunophenotype of a cell, which is indicative of cell lineage identity as well as the degree of maturation. Modern flow cytometers allow the parallel inspection of 8-10 markers. Leukaemic cells show aberrations in their immunophenotype, which can be broadly categorised as follows: […] Flow cytometry is a crucial tool for detection, characterisation as well as quantification of healthy and malignant cell populations. Depending on the respective disorder, it plays an essential or supporting role for classification and differential diagnostics. In a myriad of haematological neoplasms, it has a pivotal function in the assessment of response, disease kinetics and especially in AML also in the detection of minimal/measurable residual disease (MRD).
- #1 Acute myeloid leukaemia (AML) tests | Blood Cancer UKhttps://bloodcancer.org.uk/understanding-blood-cancer/leukaemia/acute-myeloid-leukaemia/aml-symptoms-diagnosis/tests/
Tests can be done on a sample of your blood or bone marrow, to look for any changes (mutations) in the chromosomes or DNA in the abnormal cells. Sometimes these results can confirm a diagnosis of AML. […] Immunophenotyping is a test that looks at which proteins (markers) are on the surface of or inside the abnormal cells. This can help to tell doctors whether you have AML.
- #1 Acute Myeloid Leukemia (AML) Workup: Approach Considerations, Blood Studies, Flow Cytometry (Immunophenotyping)https://emedicine.medscape.com/article/197802-workup
Flow cytometry (immunophenotyping) can be used to help distinguish AML from acute lymphocytic leukemia (ALL) and further classify the subtype of AML. The immunophenotype correlates with prognosis in some instances. […] Cytogenetic studies performed on bone marrow provide important prognostic information. Guidelines from an international expert panel, on behalf of the European LeukemiaNet (ELN), recommend risk stratification for patients with AML on the basis of genetic abnormalities.
- #1 Acute Myeloid Leukemia (AML): DiagnosisÂhttps://healthlibrary.brighamandwomens.org/Conditions/Neuroscience/34,BAMLD1A
Immunophenotyping. This test measures the types and amounts of proteins called antigens on the surface of the leukemia cells. This can be used to see if you have AML, and to find out which subtype you have. Results of this test may take several days. […] Cytogenetics. For this test, cells are grown in a lab for a week or more. The chromosomes inside the cells are then stained with special dyes and viewed with a microscope. Major changes in the chromosomes can often be seen with this test. But smaller changes may not be visible. […] Fluorescence in situ hybridization (FISH). This test is another way to look for changes in chromosomes. The cells in the sample are stained with fluorescent dyes that will only attach to certain parts of chromosomes. The cells are then viewed with a microscope using a special light. This test can find some chromosome changes that can’t be seen with standard cytogenetic testing. It’s also a quicker test.
- #1 Acute Myeloid Leukemia: Diagnosis and Evaluation by Flow Cytometryhttps://www.mdpi.com/2072-6694/16/22/3855
Flow cytometry is a powerful tool for the diagnosis of AML and post-therapy monitoring. The WHO-HAEM5 and ICC include immunophenotypic characteristics in the diagnostic criteria of AML, along with cytogenetic and molecular data. Flow cytometry is essential for identifying and enumerating leukemic blasts, assigning lineage, and detecting aberrant immunophenotypic features, which are crucial for the diagnosis and subclassification of acute leukemia and monitoring the measurable residual disease (MRD) post treatment. […] The updated 2022 European LeukemiaNet (ELN) recommendations for the diagnosis and management of adult AML emphasize an integrated approach to establishing the diagnosis, with immunophenotyping by multiparametric flow cytometry required for accurate AML diagnosis. The recommended panels comprise markers for precursor, myeloid, monocytic, megakaryocytic, and erythroid populations, as well as lineage markers for myeloid, T-cell, and B-cell lineages. Standardization of these panels will ensure consistent and reliable diagnosis across different clinical settings. […] Recent advancements have integrated machine learning algorithms into flow cytometry, enhancing the precision and efficiency of data analysis and enabling more accurate diagnosis and classification of AML.
- #1 The power and potential of integrated diagnostics in acute myeloid leukaemiahttps://pmc.ncbi.nlm.nih.gov/articles/PMC6973013/
Cytogenetics encompasses the techniques of chromosome analysis and fluorescence in situ hybridisation (FISH). Chromosome analysis is performed by chromosome banding of metaphases. Nonmalignant cells generally have a normal karyotype (46,XX or 46,XY), while the leukaemic karyotype might show acquired numerical or structural chromosomal aberrations. […] The use of so-called 24-colour FISH allows characterisation/validation of complex aberrations found in chromosome analysis after banding. While chromosome analysis enables a genome-wide, comprehensive evaluation, FISH provides a targeted, but fast approach. Subtypes of MDS and acute leukaemia are defined by specific cytogenetic aberrations. Beside its relevance for WHO classification, the most crucial role for cytogenetics in acute leukaemia is prognostic stratification.
- #1 Acute Myeloid Leukemia – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK507875/
Select appropriate induction and consolidation therapies tailored to individual patient characteristics and disease risk for patients with acute myeloid leukemia. […] Collaborate with multidisciplinary healthcare teams to develop comprehensive care plans and provide support for patients throughout their acute myeloid leukemia journey. […] Characteristic laboratory findings indicative of auto-tumor lysis, stemming from high tumor burden and rapid cell turnover, often include elevated LDH, uric acid, potassium, and phosphorus levels. […] Collectively, the presence of 20% or more blasts in peripheral blood, as confirmed by immunophenotyping (flow cytometry), is diagnostic of AML. […] Following the confirmation of an AML diagnosis, recommended tests should be ordered, including electrocardiography (ECG) and 2-dimensional (2D) echocardiography, to anticipate potential cardiotoxic effects (eg, from anthracycline therapies).
- #1 Tests for acute myeloid leukaemia (AML) | Cancer Research UKhttps://www.cancerresearchuk.org/about-cancer/acute-myeloid-leukaemia-aml/getting-diagnosed/tests-acute-myeloid-leukaemia
FISH is another type of test looking at gene and chromosome changes. The FISH technique uses a special fluorescent dye. This makes it easier to see particular gene and chromosome changes. […] This is a different test to pick up gene abnormalities. Genes are coded messages made of DNA that tell cells how to behave. […] Lumbar puncture is a test to check whether leukaemia cells have spread to the fluid that circulates around the brain and spinal cord. […] You might have a chest x-ray to check for signs of infection if you have symptoms. […] You might have an ultrasound to look for changes in your lymph nodes, liver or spleen. […] You might have a CT scan to look for swollen (enlarged) lymph nodes and infections. […] Your GP should arrange for you to have a blood test or see a blood specialist (haematologist) if you have symptoms that could be due to acute myeloid leukaemia (AML). […] Chemotherapy is the main treatment for acute myeloid leukaemia (AML). Find out how your doctor decides your treatment, detailed information about each treatment, the side effects and follow up.
- #1 Acute Myeloid Leukemia (AML) – Hematology and Oncology – Merck Manual Professional Editionhttps://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/acute-myeloid-leukemia-aml
Bone marrow examination (aspiration and needle biopsy) is routinely done. Blast cells in the bone marrow are typically between 25 and 95% in patients with AML. […] Histochemical studies, cytogenetics, immunophenotyping, and molecular biology studies help distinguish the blasts of ALL from those of AML or other diseases. […] Commonly observed cytogenetic abnormalities in AML include t(15;17), trisomy 8, t(8;21), inv(16) or t(16;16) and 11q23.3 rearrangements. […] Treatment of acute myeloid leukemia depends on the patient’s overall medical condition. […] In medically fit patients, initial treatment is induction chemotherapy to try to induce complete remission. […] Complete remission is defined as 5% blast cells in the bone marrow, absolute neutrophil count 1000/mcL (1 109/L), platelet count 100,000/mcL (100 109/L), and independence from blood transfusion.
- #1 The power and potential of integrated diagnostics in acute myeloid leukaemiahttps://pmc.ncbi.nlm.nih.gov/articles/PMC6973013/
Molecular genetics has rapidly evolved into an indispensable diagnostic discipline and has brought about major advances in our understanding of the molecular landscape of cancers, including AML. It has significantly contributed to optimisation of not only classification, but also of prognostication and residual disease monitoring. Moreover, it has aided the development of targeted therapeutics and is increasingly used as a therapeutic decision-making tool. […] With respect to AML diagnostics, polymerase chain reaction (PCR)-based approaches as well as next-generation sequencing (NGS) represent the gold standard. […] In conclusion, state-of-the-art classification in AML in accordance with the WHO guidelines and also for ELN prognostication relies on the diagnostic disciplines of cytomorphology, immunophenotyping, cytogenetics and molecular genetics. A combined and interdisciplinary approach is needed to harmonise reports and increase the quality of any single method by implementation of knowledge already available from others. […] Integrated diagnostics should assist treatment decision especially in patients above the age of 65. This is underlined by a recent study that showed improved outcome for patients 65 years with adverse cytogenetics under azacytidine treatment compared to conventional therapy.
- #1 Acute Myeloid Leukemia (AML): DiagnosisÂhttps://healthlibrary.brighamandwomens.org/Conditions/Neuroscience/34,BAMLD1A
Polymerase chain reaction (PCR). This is a very sensitive test that can find even very low levels of leukemia cells in a test sample. It works by increasing the amount of genetic material in the sample so that it can be found. This test can find small levels of chromosome changes that other tests cant find. […] Next generation sequencing. This is a broad term to describe multiple different sequencing methods used to find abnormal cancer cells. Lab tests are used to look at the order (sequence) of DNA and RNA cells. Comparisons can then be made in the order of cancer cells with those of normal cells to find genetic changes. These tests can help determine prognosis and types of treatment used. […] Finding the gene changes in your leukemia cells helps your healthcare provider know if you have AML and the exact type of AML you have. […] When your healthcare provider has the results of your tests, they will contact you with the results. Your provider will talk with you about other tests you may need if AML is found. Make sure you understand the results and what follow-up you need.
- #1 Diagnosing Acute Myeloid Leukemia | NYU Langone Healthhttps://nyulangone.org/conditions/acute-myeloid-leukemia/diagnosis
If your doctor suspects the cancer has spread to the central nervous system, he or she may perform a lumbar puncture. This procedure is done at the hospital using a local anesthetic. A specialist inserts a small needle into the lower back to withdraw spinal fluid, which is examined in a laboratory. […] Knowing whether the cancer cells carry any abnormal chromosomes enables your doctor to better determine your prognosis. […] At NYU Langone, your doctor orders a test called fluorescence in situ hybridization (FISH), which can detect chromosomal changes that typically go undetected by a conventional chromosomal analysis. […] Your doctors may also perform a reverse transcription-polymerase chain reaction test to look for certain genetic mutations and translocationswhen genes or parts of genes switch places on the chromosomes of leukemia cells. […] Flow cytometry detects proteins that are present on the surface of leukemia cells. […] Molecular studies are laboratory tests that identify changes in DNA.
- #1 Acute Myeloid Leukemia Treatment (PDQ®) – NCIhttps://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq
Approximately half of patients with AML will harbor chromosomal abnormalities; therefore, conventional cytogenetic analysis remains mandatory in the evaluation of suspected AML. […] With the routine use of molecular diagnostics, the identification of recurrent somatic pathogenic variants in NPM1, FLT3, CEPBA, RUNX1, and other genes has become a routine part of determining prognosis. […] Cytogenetic and molecular analyses provide the strongest prognostic information available, predicting outcome of both remission induction and consolidation therapy. […] Cytogenic and molecular information has been combined to form distinct prognostic groups.
- #1 Acute myeloid leukemia – Wikipediahttps://en.wikipedia.org/wiki/Acute_myeloid_leukemia
The WHO classification of AML attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. […] The revised fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues was released in 2016. […] The goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure. […] The specific type of postremission therapy is individualized based on a person’s prognostic factors and general health. […] For good-prognosis leukemias (i.e. inv(16), t(8;21), and t(15;17)), people will typically undergo an additional three to five courses of intensive chemotherapy, known as consolidation chemotherapy.
- #1 Acute myeloid leukemia (AML) – Leukaemia Foundationhttps://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/acute-myeloid-leukaemia/
Acute myeloid leukaemia (AML) is a type of cancer that affects the blood and bone marrow. AML is not a single disease. It is the name given to a group of leukaemias that develop in the myeloid cell line in the bone marrow. Myeloid cells are red blood cells, platelets and all white blood cells excluding lymphocytes. […] AML is classified into eight different subtypes based on the appearance of the leukaemic cells under the microscope. Each subtype provides information on the type of blood cell involved and the point at which it stopped maturing properly in the bone marrow. This is known as the French-American-British (FAB) classification system. […] The current World Health Organisationâs classification system for AML uses additional information obtained from more specialised laboratory techniques, like genetic studies, to classify AML more precisely. This information also provides more reliable information regarding the likely course (prognosis), of a particular subtype of AML, and the best way to treat it.
- #1 What to Expect After an Acute Myeloid Leukemia Diagnosishttps://resources.healthgrades.com/right-care/leukemia/what-to-expect-after-an-acute-myeloid-leukemia-diagnosis
For AML, doctors rely on subtype classifications that describe how many healthy blood cells are present, how the leukemia (abnormal) cells appear and how many there are, changes in their chromosomes, and if there are any genetic abnormalities marking the leukemia cells. […] The leukemia is classified as subtype M0 to M7, according to the French-American-British classification system. M0 being the earliest of the subtypesâthe least abnormal. […] Another way to classify AML is the WHO (World Health Organization) system, which carefully describes the genetics of the abnormal blood cells. AML cell genetics are complex, but they also determine the behavior of the cells and what types of treatment might work best for you. Knowing the genetic details and cell markers helps your doctor plan treatment with the best chances of success.
- #1 Acute myelogenous leukemia – Diagnosis and treatment – Mayo Clinichttps://www.mayoclinic.org/diseases-conditions/acute-myelogenous-leukemia/diagnosis-treatment/drc-20369115
In the lab, tests can look for DNA changes in the bone marrow cells. Which DNA changes are present in your bone marrow cells are an important part of diagnosing AML. The results can help your healthcare team create a treatment plan. […] Sometimes, a lumbar puncture may be needed if there’s concern that the leukemia has spread to the brain and spinal cord. A lumbar puncture also is called a spinal tap. It removes a sample of the fluid that surrounds the brain and spinal cord. A small needle is inserted into the lower back to remove a fluid sample. The sample is sent to a lab. […] Imaging tests make pictures of the body. For AML, imaging tests might make pictures of the brain, if there’s concern that the leukemia cells have spread there. Imaging might include CT or MRI. If there’s concern that the leukemia might have spread to another part of the body, imaging might be done with a positron emission tomography scan, also called a PET scan.
- #1 Tests for Acute Myeloid Leukemia (AML) | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-diagnosed.html
FISH can be used to look for changes in specific genes or parts of chromosomes. […] Other types of lab tests can also be done on the samples to look for specific gene or other changes in the leukemia cells. […] Some of the changes found on these types of tests can help doctors learn more about the leukemia, and some can even help tell if certain treatments are likely to be helpful. […] Imaging tests often aren’t helpful in diagnosing AML. […] When imaging tests are done in people with AML, it’s most often to look for infections or other problems, rather than to look for leukemia itself.
- #1 Acute myeloid leukemia diagnosis – Leukaemia Foundationhttps://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/acute-myeloid-leukaemia/diagnosis/
Once an AML diagnosis is made, blood and bone marrow cells are examined further using special laboratory tests. These include immunophenotyping and cytogenetic tests. These tests provide more information about the exact type of disease you have, the likely course of your disease and the best way to treat it. […] Tests may be conducted to provide information on your general health and how your vital organs are functioning. These include a combination of further blood tests and imaging tests (x-rays, scans and ECG). These results will provide a baseline of your disease and general health which will be compared with later results to assess how well you are progressing and responding to treatment.
- #1 Acute myeloid leukaemia – Symptoms, diagnosis and treatment | BMJ Best Practicehttps://bestpractice.bmj.com/topics/en-gb/274?locale=fa
Acute myeloid leukaemia (AML) is a life-threatening haematological malignancy that predominantly occurs in older adults. […] Work-up includes bone marrow aspirate and trephine biopsy. Cytogenetic analysis and molecular genetic testing can inform diagnosis, prognosis, and treatment. […] Diagnostic investigations include FBC with differential, peripheral blood smear, coagulation panel, serum electrolytes, serum uric acid, serum lactate dehydrogenase (LDH), renal function, liver function tests, bone marrow evaluation, and genetic testing.
- #1 How AML Subtypes Affect Outlook & Treatment | American Cancer Society | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html
The subtype of AML can be important in helping to determine a person’s prognosis (outlook). […] Prognostic factors help doctors determine a person’s risk of the leukemia coming back after treatment, and therefore if they should get more or less intensive treatment. […] AML cells can have many kinds of chromosome changes, some of which can affect a persons prognosis (outlook). […] People whose leukemia cells have certain gene mutations may have a better or worse outlook. […] How well (and how quickly) the leukemia responds to treatment also affects long-term prognosis.
- #1 Acute myeloid leukemia (AML) – Leukaemia Foundationhttps://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/acute-myeloid-leukaemia/
The most important factor in predicting prognosis in AML is the genetic make-up of the leukaemic cells. Certain cytogenetic changes are associated with a more favourable prognosis than others. This means that they are more likely to respond well to treatment, and may even be cured. […] Each year in Australia around 900 people are diagnosed with AML. Overall AML is rare disease, accounting for 0.8% of all cancers diagnosed, at a rate of 3.7 per 100,000 of population. […] AML can occur at any age but is more common in adults over the age of 60. Around 50 children (0-14 years) are diagnosed with AML in Australia each year. It occurs more frequently in males than females. […] The main symptoms of AML are caused by a lack of normal blood cells. Because AML develops quickly people usually report feeling unwell for only a short period of time (days or weeks) before they are diagnosed. Common AML symptoms may include: anaemia due to a lack of red cells, causing persistent tiredness, dizziness, paleness, or shortness of breath when physically active; frequent or repeated infections and slow healing due to a lack of normal white cells, especially neutrophils; increased or unexplained bleeding or bruising, due to a very low platelet count; bone pain, swollen lymph nodes (glands), swollen gums, chest pain and abdominal discomfort due to a swollen spleen or liver. […] Occasionally people have no symptoms at all and AML is diagnosed during a routine blood test. Some of these symptoms described may also be seen in other illnesses, including viral infections, so it is important to see your doctor so that you can be examined and treated properly.
- #1 Acute Myeloid Leukemia (AML) > Fact Sheets > Yale Medicinehttps://www.yalemedicine.org/conditions/acute-myeloid-leukemia-aml
In addition to chemotherapy and stem cell transplantation, other treatments for AML may be used, including: […] Targeted therapy, which uses drugs designed to target specific components found in cancer cells but not healthy cells. […] Sometimes, AML does not respond well to treatment or comes back after a period of remission. […] Subtypes of AML may require a different course of treatment. […] What is the outlook for people who have acute myeloid leukemia? […] The outlook for people who have AML depends on several factors, including the patients age, general health, and whether they have previously been treated with chemotherapy for another medical condition. […] The five-year survival rate for adults with AML in the U.S. is 29.5%. For children and adolescents aged 19 or younger, the five-year survival rate is 66%.
- #1 Acute Myeloid Leukemia – AML | Choose the Right Testhttps://arupconsult.com/content/acute-myeloid-leukemia
Use of bone marrow core biopsy and aspirate samples for morphologic assessment, blast enumeration, immunophenotyping, cytogenetics, and molecular genetic testing is recommended. […] Immunophenotyping of bone marrow is recommended in the evaluation of suspected AML and is used in diagnosis, risk stratification, and therapeutic decision-making. […] Cytogenetic testing is recommended as part of the evaluation of suspected AML and is used to classify AML and identify abnormalities relevant to prognosis and therapeutic decision-making. […] An evaluation of somatic molecular markers by PCR (for individual mutations) or NGS (for multigene panel testing) is recommended in all individuals with AML. […] MRD, also referred to as measurable residual disease, refers to small populations of leukemic cells that remain after treatment.
- #1 Acute Myeloid Leukemia – AML | Choose the Right Testhttps://arupconsult.com/content/acute-myeloid-leukemia
The detection of MRD may be useful in determining response, remission, or relapse; in relapse risk assessment; in prognosis; in treatment decision-making; and as a surrogate endpoint in clinical trials. […] Germline molecular genetic testing for hereditary hematologic malignancies may be informative, particularly in individuals who have been diagnosed with AML at any age.
- #1 Azthena logo with the word Azthenahttps://www.news-medical.net/health/Acute-Myeloid-Leukemia-Diagnosis.aspx
In order for a patient to be considered to be in remission after treatment, the blast percentage in the bone marrow must be less than 5%. […] These tests include staining the leukemia cells with special dyes. […] This helps in assessing the cells from the bone marrow and blood samples. These tests are helpful in determining the exact type of leukemia. […] This involves identifying the genetic blueprints of the cancer cells. The leukemia cells atypical genetic makeup that can be identified using these tests. Identifications of the genetic abnormalities help in determining treatment. […] Recognizing these changes can help identify certain types of AML and predict the possible outcome of the cancer. […] FISH can be used to look for specific changes in chromosomes. It can be used on blood or bone marrow samples. […] This is yet another DNA analysis test that can find some chromosome changes too small to be seen under a microscope.
- #1 Acute Myeloid Leukemia – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK507875/
All induction regimens discussed in forthcoming sections are potentially toxic to the bone marrow and can induce cytopenias and renal failure, particularly in the setting of either auto-tumor lysis, as discussed earlier, or TLS following chemotherapy. […] Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for AML and should be considered for any patient with intermediate- or high-risk disease who achieves complete remission. […] In young, fit individuals undergoing a 7+3 or FLAG-based induction regimen, a bone marrow biopsy should ideally be performed after induction therapy around the time of peripheral count recovery, particularly when the absolute neutrophil count exceeds 1000/L and platelet count exceeds 100 K/L with no blasts present. […] Despite achieving a complete response with optimal induction therapy, minimal residual disease often persists, necessitating consolidation therapy to mitigate the risk of relapse by eliminating residual disease. […] Prognosis in AML depends on an individual patient’s cytogenetic and molecular characterization.
- #1 The power and potential of integrated diagnostics in acute myeloid leukaemiahttps://pmc.ncbi.nlm.nih.gov/articles/PMC6973013/
The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today, state-of-the-art AML diagnostics relies on cytomorphology, cytochemistry, immunophenotyping, cytogenetics and molecular genetics. Only the integration of all of these methods allows for a comprehensive and complementary characterisation of each case, which is prerequisite for optimal AML diagnosis and management. […] Here, we will review why multidisciplinary diagnostics is mandatory today and will gain even more importance in the future, especially in the context of precision medicine. We will discuss ideas and strategies that are likely to shape and improve multidisciplinary diagnostics in AML and may even overcome some of today’s gold standards. This includes recent technical advances that provide genome-wide molecular insights. The enormous amount of data obtained by these latter techniques represents a great challenge, but also a unique chance. We will reflect on how this increase in knowledge can be incorporated into the routine to pave the way for personalised medicine in AML.
- #1 Toward Integrated Genomic Diagnosis in Routine Diagnostic Pathology by the World Health Organization Classification of Acute Myeloid Leukemiahttps://www.scientificarchives.com/article/toward-integrated-genomic-diagnosis-in-routine-diagnostic-pathology-by-the-world-health-organization-classification-of-acute-myeloid-leukemia
Most significantly, in 2020, we understand AML to be an aggressive clonal hematologic malignancy characterized by marked heterogeneity in genetic and clinical features, with this single disease comprised of numerous subtypes, with different prognosis and treatment options. […] Precise classification of AML, necessary for risk stratification and therapy, is best achieved by the WHO2016/2017 classification, which requires not only microscopic skills, but also availability and collaboration for multiple modalities of tests, including clinical history, laboratory hematology, FCI, cytogenetics, and molecular genetics. […] The presence of the t(8;21), t(15;17), t(16;16) or inv(16) abnormalities is diagnostic of AML even if blasts are less than 20%. […] Cytogenetics analysis is essential, with molecular analysis for genetic mutations.
- #1 Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing | Leukemiahttps://www.nature.com/articles/s41375-020-0762-8
HAMLET was developed as a bioinformatics pipeline to call all relevant information for diagnosis and prognosis of AML from raw mRNAseq data. HAMLET integrates four modules using algorithms to detect fusion genes (STARfusionFusionCatcher), small variants (VARSCAN), large tandem duplications (ReSCU), and gene expression. […] HAMLET accurately detected all recurrent fusion genes that were predicted by metaphase cytogenetics in 24 cases. […] The VARSCAN component of HAMLET identified 246 small variants in the selected 13 AML genes with 100% specificity. […] Reliable detection of the common tandem duplications in exon 14-15 of FLT3 is of special importance in AML diagnostics since presence of the FLT3-ITD is an indication for therapy with a tyrosine kinase inhibitor. […] The intrinsic quantification of gene expression by mRNAseq readily permits measurement of EVI1 expression, whose overexpression heralds a very poor prognosis even in the absence of structural aberrations involving 3q26. […] HAMLET appears to be a reliable approach to obtain comprehensive genetic information with prognostic and therapeutic relevance for AML in a single assay.
- #1 Diagnosis | Stanford Health Carehttps://stanfordhealthcare.org/medical-conditions/cancer/acute-myeloid-leukemia-aml/patient-care-resources/diagnosis.html
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. […] At Stanford, we tailor the diagnostic phase of acute myeloid leukemia care to each patient. If you need further testing to complete your diagnosis, your doctor and care team will work with you to determine which tests you need. Tests may include: […] Genetic testing is a medical test that identifies changes in genes, chromosomes, or proteins. For acute myeloid leukemia, genetic testing can show whether you have inherited mutations in genes related to the disease. […] Blood tests can provide a variety of information, helping to establish your diagnosis and plan your course of acute myeloid leukemia treatment.
- #1https://www.nhs.uk/conditions/acute-myeloid-leukaemia/treatment/
Acute myeloid leukaemia (AML) is an aggressive cancer that grows quickly, so treatment will usually begin a few days after a diagnosis has been confirmed. […] The initial treatment you have for AML will largely depend on whether you’re fit enough to have intensive chemotherapy, or whether treatment at a lower dosage is recommended. […] If there’s no AML left after induction chemotherapy, the next stage of treatment is consolidation. […] Clinical trials are studies that use new and experimental techniques to see how well they work in treating, and possibly curing, AML. […] Your care team can tell you whether there are any clinical trials available in your area, and can explain the benefits and risks involved.
- #1 Acute myeloid leukaemia âDiagnosis and management – Medical Independenthttps://www.medicalindependent.ie/clinical-news/acute-myeloid-leukaemia-diagnosis-and-management/
Acute myeloid leukaemia (AML) is an aggressive form of blood cancer that is derived from the over proliferation of 20 per cent of immature myeloid blood cells in the peripheral blood, bone marrow or extramedullary tissues. […] Diagnosis of AML is a rapid process, which requires a comprehensive assessment of the patient. Multiple tests and procedures are required to yield a diagnosis. Initially, a full blood count with blood film is requested and reviewed by a haematologist, and a bone marrow aspirate and trephine biopsy, immunophenotyping by flow cytometry, and cytogenetic analysis is sent from the marrow sample. […] All the outlined tests and procedures are completed rapidly to establish a diagnosis and thereby create a treatment plan individually tailored to suit each patient.
- #1 Acute myeloid leukaemia | Guide to best cancer care, diagnosis and treatment | Cancer Councilhttps://www.cancer.org.au/cancercareguides/acute-myeloid-leukaemia
It can be overwhelming after being told that you have or may have acute myeloid leukaemia (AML). A haematologist will do some tests to confirm if you have AML (and acute promyelocytic leukaemia [APL] which is a special sub-set of AML). This process of working out if you have a medical problem is called making a diagnosis. […] Tests to see if you have APL should be done immediately and the results should be available as soon as possible. If you have AML, other test results to help start your treatment should be available within 72 hours of your haematologist appointment. […] Treatment should start promptly once a diagnosis is made and a treatment plan is confirmed.
- #1 Acute Myeloid Leukemia (AML) Differential Diagnoseshttps://emedicine.medscape.com/article/197802-differential
Pancytopenia, for example, can be caused by a large variety of diseases of varying severity, including vitamin deficiencies and autoimmune disease. However, pancytopenia due to acute promyelocytic leukemia (APL) is a life-threatening emergency that must be aggressively treated immediately. […] The easiest way to avoid misdiagnosis is to review the peripheral blood smear at the time of initial evaluation of all patients with hematologic disorders. […] Another condition that should be considered in the evaluation of AML is agranulocytosis, a severe subset of neutropenia. […] The 2016 World Health Organization (WHO) category of acute myeloid leukemia and related neoplasms contains related neoplasms that derive from immature cells with evidence of myeloid differentiation, or from precursors of plasmacytoid dendritic cells.
- #2 Acute Myeloid Leukemia (AML) Diagnosis | LLS.orghttps://www.lls.org/leukemia/acute-myeloid-leukemia/diagnosis
An accurate diagnosis of the type of leukemia is important. The exact diagnosis helps the doctor to estimate how the disease will progress and determine the appropriate treatment. […] Diagnosing acute myeloid leukemia (AML) and your AML subtype usually involves a series of tests. Some of these tests may be repeated during and after therapy to measure the effects of treatment. […] Blood and bone marrow tests are used to diagnose AML and the AML subtype. A change in the number and appearance of blood cells helps to make the diagnosis. […] Your doctor will work with a hematopathologist to confirm the diagnosis. For a person to be diagnosed with AML, generally 20 percent or more of the cells in the bone marrow or blood must be myeloblasts. […] Chromosomal changes and genetic mutations are an important prognostic factor for predicting remission rates, relapse risks and survival outcomes. However, not all patients have a chromosomal abnormality, and patients may have different gene mutations from other AML patients. Your doctor will perform a molecular analysis on your cells to identify specific genetic changes.
- #2 Acute Myeloid Leukemia (AML): Symptoms, Treatment & Prognosishttps://my.clevelandclinic.org/health/diseases/6212-acute-myeloid-leukemia-aml
Acute myeloid leukemia (AML) is a rare cancer that affects your bone marrow and blood. […] Healthcare providers use several tests to diagnose AML, including genetic tests to identify AML type. Providers typically start with a physical examination. They check for bruises, bleeding or infection. They check for enlarged (swollen) organs, specifically your liver, spleen and lymph nodes. […] Medical pathologists do genetic tests to identify AML type. They may examine certain chromosomes or genes to see if theyâve mutated or changed. Knowing AML type helps providers decide which treatment is most likely to eliminate AML. […] Treatments may include chemotherapy, targeted therapy (including monoclonal antibody therapy) or allogeneic stem cell transplantation. […] Currently, allogeneic stem cell transplantation is the only way to cure acute myeloid leukemia.
- #2 Tests for Acute Myeloid Leukemia (AML) | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-diagnosed.html
The percentage of blasts in the bone marrow or blood is particularly important in diagnosing AML. […] At least 20% blasts in the marrow or blood is generally required to diagnose AML, if there are no diagnostic gene or chromosome changes in the AML cells. […] AML can also be diagnosed if there are at least 10% blasts in the bone marrow or blood, AND the AML cells have certain diagnostic gene or chromosome changes. […] Other lab tests may also be done to confirm an AML diagnosis or to learn more about it. […] Some tests look at the chromosomes inside the cells. […] Recognizing these changes can help identify certain types of AML and might also be important in determining a persons outlook and treatment options. […] Cytogenetics (karyotyping): In this test, the cells are looked at with a microscope to see if the chromosomes have any abnormalities.
- #2 Acute myeloid leukemia – Wikipediahttps://en.wikipedia.org/wiki/Acute_myeloid_leukemia
The basis of allogenic stem cell transplantation is on a graft versus leukemia effect whereby graft cells stimulate an immune response against leukemia cells. […] Target therapy is a type of treatment that uses drugs or other substances to target specific molecules that cancer cells need to survive and spread. […] A complete blood count, which is a blood test, is one of the initial steps in the diagnosis of AML. […] A blood film may show leukemic blast cells. […] Inclusions within the cells called Auer rods, when seen, make the diagnosis highly likely. […] Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. […] The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. […] The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. […] The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.
- #2 Acute Myeloid Leukemia (AML): DiagnosisÂhttps://healthlibrary.brighamandwomens.org/Conditions/Neuroscience/34,BAMLD1A
Immunophenotyping. This test measures the types and amounts of proteins called antigens on the surface of the leukemia cells. This can be used to see if you have AML, and to find out which subtype you have. Results of this test may take several days. […] Cytogenetics. For this test, cells are grown in a lab for a week or more. The chromosomes inside the cells are then stained with special dyes and viewed with a microscope. Major changes in the chromosomes can often be seen with this test. But smaller changes may not be visible. […] Fluorescence in situ hybridization (FISH). This test is another way to look for changes in chromosomes. The cells in the sample are stained with fluorescent dyes that will only attach to certain parts of chromosomes. The cells are then viewed with a microscope using a special light. This test can find some chromosome changes that can’t be seen with standard cytogenetic testing. It’s also a quicker test.
- #2 Acute Myeloid Leukemia (AML): DiagnosisÂhttps://healthlibrary.brighamandwomens.org/Conditions/Neuroscience/34,BAMLD1A
Polymerase chain reaction (PCR). This is a very sensitive test that can find even very low levels of leukemia cells in a test sample. It works by increasing the amount of genetic material in the sample so that it can be found. This test can find small levels of chromosome changes that other tests cant find. […] Next generation sequencing. This is a broad term to describe multiple different sequencing methods used to find abnormal cancer cells. Lab tests are used to look at the order (sequence) of DNA and RNA cells. Comparisons can then be made in the order of cancer cells with those of normal cells to find genetic changes. These tests can help determine prognosis and types of treatment used. […] Finding the gene changes in your leukemia cells helps your healthcare provider know if you have AML and the exact type of AML you have. […] When your healthcare provider has the results of your tests, they will contact you with the results. Your provider will talk with you about other tests you may need if AML is found. Make sure you understand the results and what follow-up you need.
- #2 Acute myeloid leukemia (AML) – Leukaemia Foundationhttps://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/acute-myeloid-leukaemia/
Acute myeloid leukaemia (AML) is a type of cancer that affects the blood and bone marrow. AML is not a single disease. It is the name given to a group of leukaemias that develop in the myeloid cell line in the bone marrow. Myeloid cells are red blood cells, platelets and all white blood cells excluding lymphocytes. […] AML is classified into eight different subtypes based on the appearance of the leukaemic cells under the microscope. Each subtype provides information on the type of blood cell involved and the point at which it stopped maturing properly in the bone marrow. This is known as the French-American-British (FAB) classification system. […] The current World Health Organisationâs classification system for AML uses additional information obtained from more specialised laboratory techniques, like genetic studies, to classify AML more precisely. This information also provides more reliable information regarding the likely course (prognosis), of a particular subtype of AML, and the best way to treat it.
- #2 How AML Subtypes Affect Outlook & Treatment | American Cancer Society | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html
In both systems, the percentage of blasts (very immature blood cells) in the bone marrow or blood is important in diagnosing AML. […] If the AML cells have certain gene or chromosome changes (see below), usually at least 10% of the cells in the bone marrow or blood must be blasts. […] If there are no major gene or chromosome changes in the AML cells, usually at least 20% of the cells in the bone marrow or blood must be blasts to diagnose AML. […] The classification of AML has become more complex over time, as doctors have learned more about the genetic changes inside AML cells. […] The International Consensus Classification (ICC) can also be used to determine the AML subtype. […] Like the WHO classification, its based mainly on the gene or chromosome changes in the AML cells, but other factors can be important, too.
- #2 Tests for acute myeloid leukaemia (AML) | Cancer Research UKhttps://www.cancerresearchuk.org/about-cancer/acute-myeloid-leukaemia-aml/getting-diagnosed/tests-acute-myeloid-leukaemia
FISH is another type of test looking at gene and chromosome changes. The FISH technique uses a special fluorescent dye. This makes it easier to see particular gene and chromosome changes. […] This is a different test to pick up gene abnormalities. Genes are coded messages made of DNA that tell cells how to behave. […] Lumbar puncture is a test to check whether leukaemia cells have spread to the fluid that circulates around the brain and spinal cord. […] You might have a chest x-ray to check for signs of infection if you have symptoms. […] You might have an ultrasound to look for changes in your lymph nodes, liver or spleen. […] You might have a CT scan to look for swollen (enlarged) lymph nodes and infections. […] Your GP should arrange for you to have a blood test or see a blood specialist (haematologist) if you have symptoms that could be due to acute myeloid leukaemia (AML). […] Chemotherapy is the main treatment for acute myeloid leukaemia (AML). Find out how your doctor decides your treatment, detailed information about each treatment, the side effects and follow up.
- #2 Acute Myeloid Leukemia – StatPearls – NCBI Bookshelfhttps://www.ncbi.nlm.nih.gov/books/NBK507875/
Select appropriate induction and consolidation therapies tailored to individual patient characteristics and disease risk for patients with acute myeloid leukemia. […] Collaborate with multidisciplinary healthcare teams to develop comprehensive care plans and provide support for patients throughout their acute myeloid leukemia journey. […] Characteristic laboratory findings indicative of auto-tumor lysis, stemming from high tumor burden and rapid cell turnover, often include elevated LDH, uric acid, potassium, and phosphorus levels. […] Collectively, the presence of 20% or more blasts in peripheral blood, as confirmed by immunophenotyping (flow cytometry), is diagnostic of AML. […] Following the confirmation of an AML diagnosis, recommended tests should be ordered, including electrocardiography (ECG) and 2-dimensional (2D) echocardiography, to anticipate potential cardiotoxic effects (eg, from anthracycline therapies).
- #2 How AML Subtypes Affect Outlook & Treatment | American Cancer Society | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html
The subtype of AML can be important in helping to determine a person’s prognosis (outlook). […] Prognostic factors help doctors determine a person’s risk of the leukemia coming back after treatment, and therefore if they should get more or less intensive treatment. […] AML cells can have many kinds of chromosome changes, some of which can affect a persons prognosis (outlook). […] People whose leukemia cells have certain gene mutations may have a better or worse outlook. […] How well (and how quickly) the leukemia responds to treatment also affects long-term prognosis.
- #2 Acute Myeloid Leukemia Treatment (PDQ®) – NCIhttps://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq
Approximately half of patients with AML will harbor chromosomal abnormalities; therefore, conventional cytogenetic analysis remains mandatory in the evaluation of suspected AML. […] With the routine use of molecular diagnostics, the identification of recurrent somatic pathogenic variants in NPM1, FLT3, CEPBA, RUNX1, and other genes has become a routine part of determining prognosis. […] Cytogenetic and molecular analyses provide the strongest prognostic information available, predicting outcome of both remission induction and consolidation therapy. […] Cytogenic and molecular information has been combined to form distinct prognostic groups.
- #2 Acute Myeloid Leukemia Diagnosis | MD Anderson Cancer Centerhttps://www.mdanderson.org/cancer-types/acute-myeloid-leukemia/acute-myeloid-leukemia-diagnosis.html
In untreated AML, the disease is newly diagnosed. It has not been treated except to relieve signs and symptoms such as fever, bleeding, or pain, and the following are true: The complete blood count is abnormal. At least 20% of the cells in the bone marrow are blasts (leukemia cells) or there are certain gene changes. There are signs or symptoms of leukemia. […] In AML in remission, the disease has been treated and the following are true: The complete blood count is normal. Less than 5% of the cells in the bone marrow are blasts (leukemia cells). There are no signs or symptoms of leukemia in the brain and spinal cord or elsewhere in the body. […] After treatment with chemotherapy, some patients with newly diagnosed AML will not go into remission. This is called refractory cancer. In contrast, relapsed or recurrent AML is cancer that has recurred (come back) after remission.
- #2 Toward Integrated Genomic Diagnosis in Routine Diagnostic Pathology by the World Health Organization Classification of Acute Myeloid Leukemiahttps://www.scientificarchives.com/article/toward-integrated-genomic-diagnosis-in-routine-diagnostic-pathology-by-the-world-health-organization-classification-of-acute-myeloid-leukemia
Most significantly, in 2020, we understand AML to be an aggressive clonal hematologic malignancy characterized by marked heterogeneity in genetic and clinical features, with this single disease comprised of numerous subtypes, with different prognosis and treatment options. […] Precise classification of AML, necessary for risk stratification and therapy, is best achieved by the WHO2016/2017 classification, which requires not only microscopic skills, but also availability and collaboration for multiple modalities of tests, including clinical history, laboratory hematology, FCI, cytogenetics, and molecular genetics. […] The presence of the t(8;21), t(15;17), t(16;16) or inv(16) abnormalities is diagnostic of AML even if blasts are less than 20%. […] Cytogenetics analysis is essential, with molecular analysis for genetic mutations.
- #3 Acute myeloid leukemia – Wikipediahttps://en.wikipedia.org/wiki/Acute_myeloid_leukemia
The basis of allogenic stem cell transplantation is on a graft versus leukemia effect whereby graft cells stimulate an immune response against leukemia cells. […] Target therapy is a type of treatment that uses drugs or other substances to target specific molecules that cancer cells need to survive and spread. […] A complete blood count, which is a blood test, is one of the initial steps in the diagnosis of AML. […] A blood film may show leukemic blast cells. […] Inclusions within the cells called Auer rods, when seen, make the diagnosis highly likely. […] Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. […] The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. […] The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. […] The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.
- #3 Acute Myeloid Leukemia (AML): DiagnosisÂhttps://healthlibrary.brighamandwomens.org/Conditions/Neuroscience/34,BAMLD1A
Immunophenotyping. This test measures the types and amounts of proteins called antigens on the surface of the leukemia cells. This can be used to see if you have AML, and to find out which subtype you have. Results of this test may take several days. […] Cytogenetics. For this test, cells are grown in a lab for a week or more. The chromosomes inside the cells are then stained with special dyes and viewed with a microscope. Major changes in the chromosomes can often be seen with this test. But smaller changes may not be visible. […] Fluorescence in situ hybridization (FISH). This test is another way to look for changes in chromosomes. The cells in the sample are stained with fluorescent dyes that will only attach to certain parts of chromosomes. The cells are then viewed with a microscope using a special light. This test can find some chromosome changes that can’t be seen with standard cytogenetic testing. It’s also a quicker test.
- #3 How AML Subtypes Affect Outlook & Treatment | American Cancer Society | American Cancer Societyhttps://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html
The subtype of AML can be important in helping to determine a person’s prognosis (outlook). […] Prognostic factors help doctors determine a person’s risk of the leukemia coming back after treatment, and therefore if they should get more or less intensive treatment. […] AML cells can have many kinds of chromosome changes, some of which can affect a persons prognosis (outlook). […] People whose leukemia cells have certain gene mutations may have a better or worse outlook. […] How well (and how quickly) the leukemia responds to treatment also affects long-term prognosis.
- #3 Acute Myeloid Leukemia (AML) – Hematology and Oncology – Merck Manual Professional Editionhttps://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/acute-myeloid-leukemia-aml
Bone marrow examination (aspiration and needle biopsy) is routinely done. Blast cells in the bone marrow are typically between 25 and 95% in patients with AML. […] Histochemical studies, cytogenetics, immunophenotyping, and molecular biology studies help distinguish the blasts of ALL from those of AML or other diseases. […] Commonly observed cytogenetic abnormalities in AML include t(15;17), trisomy 8, t(8;21), inv(16) or t(16;16) and 11q23.3 rearrangements. […] Treatment of acute myeloid leukemia depends on the patient’s overall medical condition. […] In medically fit patients, initial treatment is induction chemotherapy to try to induce complete remission. […] Complete remission is defined as 5% blast cells in the bone marrow, absolute neutrophil count 1000/mcL (1 109/L), platelet count 100,000/mcL (100 109/L), and independence from blood transfusion.