Acute myeloid leukaemia Flashcards
What is acute myeloid leukaemia
Bone marrow malignancy of myeloid cells causing immature cells arrested in development -> blood, impair haematopoiesis -> anaemia, bleeding, infections
Blast accumulation -> bone marrow failure
Genetic diseases ass w AML
Downs syndrome, Fanconi anaemia, Bloom syndrome
What genetics are ass w AML
FLT3, NPM1, CEBPA, RUNX1 mutations
Environemental factors ass w AML
Chemicals and radiation esp benzene and other petroleum products
Ionising radiation eg atomic bomb, therapeutic radiation
What lifestyle factor increases AML risk
Smoking
Dose dependent
Decreases after cessation
What treamtnet esp increases AML risk
Chemotherapy esp alkylating agents and topoisomerase II inhibtprs
WHat disroders increase risk of AML
Myedodysplastic sundrome or chronic myeloproliferative disorders
What is the first hit AML
First hit - mutation - proliferative advantage -> clonap expansion of haematopoietic stem cell in FLT3, NPM1, DNMT3A
What is second hit AML genes and how
Mutation in one of clonally expanded cells from first mutation affecting gene in haemtopoietic differntiation -> proliferation and blocking differntiation -> accumulation of immature blasts
RUNX1 or CEBPA
How do immature blasts cause bone marrow failure
Prevent normal haematopoiesis
WHO classification of AML tpyes
AML with recurrent genetic abnormalities
AML with myelodysplasia-related features
Therapy-related AML and MDS
AML, not otherwise specified
Myeloid sarcoma
Myeloid proliferations related to Down syndrome
AML subtypes in FAB classification
M0: Acute myeloblastic leukaemia without maturation
M1: Acute myeloblastic leukaemia with minimal granulocyte maturation
M2: Acute myeloblastic leukaemia with granulocyte maturation
M3: Acute promyelocytic leukaemia (APL)
M4: Acute myelomonocytic leukaemia
M5: Acute monocytic leukaemia
M6: Acute erythroid leukaemia
M7: Acute megakaryoblastic leukaemia
Clinical features of AML
Fever
Anaemia
Thrombocytopenia (ecchymoses, petechiae, musocal bleeds)
Coagulopathy
Bone pain
Leukaemia cutis
Gingival hypertrophy
CNS involvement
Organomegaly
Clinical history with AML
Frequent infections/fever
SOB, palpitations, weakness, fatigue, dizziness, pallor
TP - ecchymoses, petechiae, gingival bleed, epistacxis, menorrhagie
DIC - bleedng (only APML)
Bone pain - sternal discomfort, aching in extermitis
Nodular violaceous lesions on skin, gingival hypertrophy in Amonocytic or myelomonocytic
CNS involve - headahce, visual chnages, nerve palsies
Adenopathy, hepatomegaly, splenomegaly
What causes bone pain in AML
Expansion of medullary cavity by leukaemic process
FBC w AML
Normocytic, normochromic anaemia
Thrombocytopenia
Leucocyte count - low, normal or raised
What is seen on peripheral blood smear in AML
Raised myeloblasts
Auer rods
What do myeloblasts look like on blood smear
Immature cells w large nuclei, prominenet nucleoli pale bkue cytoplasm w Wright Giemsa stain
What are auer rods and how look on film and what mainly seen in
Pink/red rod shaped cytoplasmic granular inclusions
Myeloperoxidase positive
Pathogonimic of myeloblasts
Mostly seen in acute promyelocytic leukaemia
What is unique to acute promyelocytic leukaemia
Bleeding secondary to DIC much more common than other AMLs
What electrolyte abnormalities are seen with increasing cell lysis in AML
Hyperphosphatemia
Hyperkalemia
hyperuricaemia
Hypocalcemia
What test confirms AML
Bone marrow aspiration and biospy
>20% myeblasts in bone marrow = confirmed
Tests for AML
Bone marrow aspiration and biopsy
FBC, coag, U+Es, LFTs
Blood smear
Immunophenotyping
Cytogenic features
Molecular studies
Immunophenotyping in AML
CD13, CD33, CD34, CD117 + HLA-DR
How is cryogenetics carried out
conventional karyotypic analysis plus reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH).
What can confirm AML on cryogenetics
The abnormalities like: t (8;21)(q22;q22), inv (16)(p13;q22), t (16;16)(p13;q22), and t (15;17)(q22;q12), define AML irrespective of the blast count.
What suggests AML in molecular studies
abnormalities in specific genes FLT3, NPM1, KIT, CEBPA, IDH1 and IDH2, p53, or RUNX1.
How differentiate from ALL
ALL is terminal deoxynucleotidyl transferase - TdT positive
What is considered complete remission from AML
<5% blast cells in bone marrow or peripheral blood
What type of AML is a medical emergency
Acute promyelocytic leukaemia
Treatment for acute promyelocytic leukaemia
Haematologicemergency -> 4U FFP correct DIC THEN
All trans retinoic acid - ATRA and arsenic
Induce maturaion of immature malignant cells
What determines the choice of chemotherapy
Cytogenetics
What are most commonly used chemotherapy drugs? Add ins for specific mutatinos?
Cytarabine and anthracyclines (daunorubicin)
Midostaurin
Ivosidenib
Enasidenib
When use haematopoeitic cell transplantation in AML
Unfavourable prognostic factors eg cytogenetics
OR remission not achieved through chemotherapy
Supportive treatment after HCT
Antibiotic prophylaxis - IV braod spec - febrile neutropenia
Trimethoprim-sulfamethoxazole for PCP if neutropenic
Imunisations
Hygeine
Surveillance
Nutritional support
Antiemetics - ondanestron
Transfusions for sev anaemia, thrombocytopenia
What use to prevent PCP in neutropenic patients
Trimethoprim-sulfamethazole
Complications of AML
Tumour lysis syndrome
Leukostasis
DIC
sev neutropenia
Sev anaemia
VTE
What is tumour lysis syndrome
After cytotoxi therapy
Rapid destructiont umour cells -> massive release of IC componenets eg K+, PO4-, nucleic acids -> circulation
Lab featires of tumour lysis syndrome
Hyperkalaemia
Hyperphosphatemia
Hypoclacemia - phosphate bind
Hyperuricaemai - nucleic acid -> uric acid
Clinical features of tumour lysis syndrome
N+V, diarrhoea
Lethargy
Haematuria
Seizures, arrhtyhmoas
Tetany, muscle cramps, paraesthesisa
AKI - CaPo4 crystals and urate
What is leukostasis
Excessive leukaemic cellls >50 -> blood viscosity
Resp or neuro distress
Clinical features of leukostasis
Chest pain
Headahce
Altered mental status
Priapism
When is neutropenia svere
<500
eg<0.5
Sev thrombocytopenia
<10,000 u/L or active bleeding
When does VTE in AML most commonly occur
First 3 months of treatment
Clinical characteristics w favourable prognosis AML
Age < 50 years
ECOG performance status score < 3 or a Karnofsky score >60 %.
No comorbidities
No previous/causative myelodysplastic syndrome or myeloproliferative neoplasm
No history of exposure to cytotoxic agents and radiation therapy
Cytogenetic features favourabole AML
MDR 1-negative phenotype
Translocations: t (8;21), inv (16), t (16;16), t (15;17)
NPM1 mutation, CEBPA mutation
What is the five year survival with AML
24%
Who gets AML
Toward the elderly
What causes acute promyelocytic leukaemia
t15:17 mutation
Acute treatment APML
Infection broad antibiotics
Transfus blood and plateltes
Haematology- chemo, bone marrow transplant
