Myeloproliferative Disorders

Myeloproliferative NeoplasmsMyeloproliferative neoplasmsClonal haematopoeitic disordersProliferation of one of myeloid lineagesGranulocyticErythroidMegakaryocyticPresence of mutated, constitutively activated tyrosine kinasesRelatively normal maturation

2Myeloproliferative neoplasmsWHO Classification of MPNChronic Myeloid leukemiaPolycythemia VeraEssential ThrombocythemiaPrimary MyelofibrosisCh Neutrophillic leukemiaCh Eosinophillic leukemia not otherwise categorizedSystemic mastocytosisMPN, unclassifiable ( ch- chronic)3

Myeloproliferative neoplasmsMyeloproliferative neoplasmsMPDPRVETMF

AMLMDSRARARSRAEB IRAEB II

CMMLCML5Myeloproliferative neoplasmsCh Myeloid leukemia (BCR-ABL positive)

Polycythemia Vera

Essential Thrombocythemia

Myelofibrosis

6Sp criteria for diagnosis & distinct ds,common features

proliferative drive in marrow

Clonal marrow hyperplasia without dysplasia

Hepatosplenomegaly EMH

Variable transformation to spent phase & acute leukemia

Hypercatabolism

Myeloproliferative neoplasmsBone marrow stem cellClonal abnormalityGranulocyte precursorsRed cell precursorsMegakaryocytesReactive fibrosisEssentialthrombocytosis(ET)Polycythaemia rubra vera(PRV)MyelofibrosisAMLChronic myeloid leukemia70%10%10%30%8CHRONIC MYELOID LEUKEMIA

DefinitionProliferation of more mature granulocytes

Ionizing radiationAcquired disease- PHILADELPHIA CHROMOSOMEt (9;22)BCR-ABL tyrosine kinase activity, uncontrolled proliferation of myeloid cells CML

Etiopathogenesis

40-60yrsInsidious onsetMarked splenomegaly dragging sensation in abdomenBone painAnemia, BleedingHypermetabolism, Hyperuricemia- gout, renal impairmentClinical FeaturesPeripheral smearAnemia leukocyte count (>50x109/L)Blasts < 5%Late precursors +Basophilia, eosinophilia platelet count

Hematological Findings

Bone marrow aspirateHypercellularM:E >20:1Blast cells < 10% (chronic phase)B, E, with precursorsmegs- normal/ Hematological Findings

serum-- uric acid, LDH, alkaline phosphatase, transcobalamine levels

LAP 0-20 (normal 40 100)Lab Findings

Clinical Course: Phases of CMLChronic phase

Median 46 yearsstabilizationBlasts < 5% in marrow

Accelerated phase

Median durationup to 1 yearBlasts>10%, 20%--myeloid/lymphoidFew weeks to monthsMarrow fibrosisfailureThrombocytopenia--bleedingPhases of CMLLeukemoid ReactionResponse of normal healthy bone marrow to various stresses

Infections

Hematological malignancies

Non - hematological malignancies

Various toxic states

Leucocytosis FDusky cyanosis (plethora)CNS- headache,dizziness,tinnitus,visual disturbancesSplenomegalyPruritisClinical Features

41RBC- >6million/cu mmHb >18gm%PCVMild to moderate leukocytosisLAP scoreBasophils Hematological FindingsBone marrowHypercellular Reticulin - fibrosisIron - nilHematological FindingsPrepolycythemic phase

Overt polycythemic phase

Spent post-polycythemic myelofibrosis phasePhases of PV

Polycythemia veraStem cell disorderNo hypoxiaErythropoietin Splenomegaly +BM-hyperplastic+1, +8, +9, 20qLAP Secondary PolycythemiaCCF, High altitude, smoking+++Absent Normal NormalNormalTypesESSENTIAL THROMBOCYTHEMIAClonal MPN

Mutations in JAK2 or MPL

Platelet count >6 lakhs/cu mm few giant forms

BM- megakaryocytic hyperplasiaFeaturesESSENTIAL THROMBOCYTHEMIA

ESSENTIAL THROMBOCYTHEMIA

PRIMARY MYELOFIBROSISMyeloproliferative disorders

Toxins

Infections EtiologyMarrow replaced by fibrosis- dry tap on aspiration

Migration of progenitor cells to liver & spleen- Extramedullary hematopoiesis

Massive splenomegaly

Clinical Findings

MYELOFIBROSISAnisopoikilocytosisTear drop RBCsNucleated RBCsTLC normal/ Shift to leftPlatelets normal /

Peripheral Smear

Tear drop cell

THANK YOU

MPS : E.T. Bleeding

BM & PS
MPS : E.T. Thrombocytosis

MPS : M.F. Organomegaly