ACUTE MYELOID LEUKAEMIA

Neoplastic proliferation of blast cells is derived from marrow myeloid elements. It is very rapidly progressive malignancy ( death in -2 months if untreated , 20% 3- yr survival a/f chemotherapy )

Incidence

1/10,000/yr Increase with age & is the commonest a/c leukaemia in adults Seen increasingly as a long-term complication of chemotherapy, eg for lymphoma Also asso: with MD $ , ionising radiation & $ eg Downs

Morphological classification

Based on WHO histological classification, which is complex & requires specialist interpretation It recognizes important prognostic information from cytogenetics & molecular genetics 5 main types AML with recurrent genetic abn AML multi-lineage dysplasia ( us 2 to preexisting MD$ ) AML, therapy related a/c leukaemia of ambiguous lineage ( both myeloid & lymphoid phenotype ) AML, other

FAB classification

M0 M1 M2 M3 M4 M5 M6 M7

-- AML undifferentiated no morphological feature to distinguish it from ALL -- AML with recognizable myeloid features s/a Auer rods -- AML with few cells differentiating to promyelocyte stage -- a/c promyelocytic leukaemia -- Myelomonocytic leukaemia -- Pure monocytic leukaemia -- a/c erythroleukaemia -- a/c megakaryoblastic leukaemia

Symptoms

Marrow failure -- -/s of anaemia, inf, bleeding DIC occurs in a/c promyelocytic L ( use of ATRA with chemotherapy reduces risk of DIC ) Infiltration -- Hepato- & splenomegaly, gum hypertrophy , skin involvement. CNS invol: at presentation is rare in AML

Acute promyelocytic leukaemia

Majority of leukaemic cells are abn hypergranular promyelocytes Auer rods & collections of Auer rods ( faggots ) common Strongly Sudan black/ peroxidase positive Characteristic chromosome abnormality t ( 15;17 ) , involving retinoic acid receptor gene alpha ( RARA) Variant M3 is hypogranular but otherwise the same

INVx

WCC often , but can be normal or low Blast cells m/b few in peripheral blood, so Dx d/p on BM biopsy Morphology : (+) of Auer rods are diagnostic of AML Cytochemistry : Sudan black ( stains lipid material in AML ), esterase ( stains monocytic variants of AML ) Cytogenetic abn : t(15:17)- a/c promyelocytic leukaemia(M3) : t(8:21) AML with diff: (M2)-better Px : inv 16 inversion of long arm of chro:16better Px AML M4 with marrow eosinophilia (M4Eo)

Complications
Infection -- is mj problem, related to both d/s & d/r tm, -- be alert to septicaemia -- m/b bacterial, fungal or viral & prophylaxis is given for each d/r tm Pitfalls -- AML itself causes fever, few antibodies r made Chemotherapy causes plasma urate levels ( from tumor lysis) -- so give allopurinol with chemotherapy , & keep well hydrated with IV fluids leucostasis may occur if WCC

T/M
Supportive care bld & plt transfusions,IV fluids & allopurinol to prevent tu lysis - insert Hickman line for venous access Chemotherapy is very intensive, resulting in long periods of marrow suppression with neutropenia + plt

The main drugs daunorubicin & cytosine arabinoside with ~5 cycles in 1 wk

BM transplant allogenic transplants from HLA-matched siblings or unrelated donors is indicated d/r 1st remission in d/s with poor Px 1) destroys leukaemic cells & immune sys: by CP + total body irradiation then repopulate the marrow by transplantation from matched donor infused IV 2) ciclosporin MTx used to reduce effect of new marrow attacking pts body C Graft vs host d/s, opportunistic inf:, relapse of L, infertility

Prognostic factors

Cytogenetics Age ( over 60 do worse ) Response to 1st course of chemotherapy Asso: d/s

ALL oPredominantly affects children oRemission m/b induced with non-myelosuppressive chemotherapy oCNS invol: common o>80% cure rate with CT oFurther classified by immunological surface markers

AML oPredominantly affects adult

oMarrow

hypoplasia required to induce remission

oCNS

invol: rare o>30% cure rate with CT oFurther classified by morphological appearance

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