#chronicmyeloidneoplasm|#CML|#MYELOPROLIFERATIVENEOPLASM|#WHOCLASSIFICATION

INTRODUCTION

Chronic myeloid leukemia is a clonal hematopoietic neoplasm characterised by BCR-ABL Fusion resulting in the formation of PHILADELPHIA CHROMOSOME.

 

 

DEFINITION

 

Chronic myeloid leukaemia is a myeloproliferative neoplasm.

Characterized by granulocytic proliferation.

 

SYNONYMS

Chronic myelogenous leukaemia, BCR-ABL POSITIVE

Chronic myelogenous leukaemia, PHILADELPHIA CHROMOSOME POSITIVE (Ph+)

Chronic myelogenous leukaemia t(9;22)(q34;q11)

Chronic granulocytic leukaemia ,BCR-ABL positive

Chronic granulocytic leukaemia, Philadelphia positive(ph+)

Chronic granulocytic leukaemia t(9;22)(q34;q11)

 

EPIDEMIOLOGY

INCIDENCE: 1-2 cases per 100000 population.

 

Males are affected than females.

 

ETIOLOGY

UNKNOWN

Radiation exposure may be implicated due to increase incidence of cases in Atomic bomb survivors.

 

CLINICAL FEATURES

Approximately 50% of newly diagnosed cases are asymptomatic.

Common clinical findings include-

Lethargy

Fatigue

Weight loss

Night seats

Anaemia

Palpable splenomegaly

 

MOLECULAR GENETICS

Phenotype of the disease depends on the site of breakpoint in the chromosome 22.

Major BCR :BCR in the exons 12-16 (b1-b5)-> abnormal fusion protein p210.

Minor BCR : BCR in the exons 1-2->short fusion protein p190 , associated with Ph+ ALL and monocytosis.

Micro BCR: BCR in the exons 17-20(c1-c4)->large fusion protein p230 associated with marked thrombocytosis and /or neutrophilic maturation.

 

GROSS PATHOLOGY

SPLEEN- solid with uniform bright red colour and light coloured regions indicate areas of infarction.

 

LIGHT MICROSCOPY

Leukemic cells are usually found in splenic cords and sinuses.

White pulp is obliterated by neoplastic cells.

 

 

DIAGNOSIS

PERIPHERAL BLOOD EXAMINATION

BONE MARROW EXAMINATION

CYTOGENETICS

MOLECULAR ANALYSIS – to identify the Ph chromosome or BCR-ABL 1 fusion.

 

 

PERIPHERAL SMEAR EXAMINATION

 

Marked leucocytosis ranging from 20-500X109/L. 

Myelocytes are more in number than Meta myelocytes (Myelocyte bulge). 

No or very minimal dysplasia. 

Low neutrophil/leukocyte alkaline phosphate. 

Absolute basophilia in almost all cases. 

Absolute eosinophilia in nearly all cases.

 

BONE MARROW

Hypercellular marrow

M:E ratio increased (up to 20:1)

15-20 cell thickness of immature para trabecular  cuff.

Low blast count

Megakaryopoiesis  increased , small hypolobated nucleus (dwarf megakaryocyte).

20-40% cases show pseudogaucher cells (characteristic crumpled tissue paper like cytoplasm which usually shows hemophagocytosis.

Thrombocytosis is commonly seen.

 

STAGES OF CML

 

 

ADJUNCTIVE TESTS

LAP score low , it can be used as screening test , however increased NAP score is seen in accelerated phase of CML.

 

Raised Vitamin B12 levels.

 

Raised Uric acid levels.

 

ANCILLARY TESTS

 

Demonstration of BCR-ABL 1 fusion gene

 

Conventional cytogenetic analysis

 

FISH with probes to BCR and ABL1

 

POLYMERASE CHAIN REACTION

 

 

 

DIFFERENTIAL DIAGNOSIS

Leukemoid reaction

 

Atypical CML (Ph negative , BCR-ABL1 negative)

 

Chronic Neutrophilic leukemia

 

CMML

 

Cellular phase of Myelofibrosis

PROGNOSIS AND PREDICTIVE FACTORS

SOKAL SCORE-Age , Spleen size , Platelet count , % blasts.

EUTOS SCORE-

 

 

REMISSION RATE IN CHRONIC MYELOID LEUKEMIA

COMPLETE HEMATOLOGICAL RESPONSE:

PARTIAL CYTOGENETIC REMISSION

COMPLETE CUYTOGENETIC REMISSION

MAJOR MOLECULAR RESPONSE

COMPLETE MOLECULAR RESPONSE