Myeloproliferarive Disorder Dr.Huda Abd Al-karim. Assistant Prof.&Consultant Oncologist

Introduction: The term myeloprolivrative disorders describes a group of conditions characterized by clonal proliferation of one or more haemopoietic components in the bone marrow and sometime the liver and the spleen. These disorders are closely related . evolution from one entity into another occurs during the course of the disease.

Cont: These disorders are: 1-polycythemia Vera. 2-idiopathic myelofibrosis. 3-essential thrombocytosis(ET). 4-chronic myeloid leukemia(CML).

Polycythemia Vera: Is a clonal disorder in which there is accumulation of phenotypically normal RBC,granulocytes,and platelets in the absence of a recognizable physiologic stimulus. It is the most common among the myeloproliferative disorder occur in 2 per 100,000 people.

Etiology: The etiology is unknown. Polycythemia vera are more resistant to apoptosis induced by erythropoeitn deprivation –due to up regulation of bcl-XL.

Clinical features: Symptoms: No specific symptoms. Most of the time it is discovered incidentally by the presence of high Hb or Hematocrit. Aquagenic pruritis is the only feature may distinguish PV from other disorder. Uncontrolled erythrocytosis can lead to neurological symptoms such as vertigo,tinnitus,headache,and visual disturbance.

Cont: Venous or arterial thrombosis may be the presenting symptoms in some patients. Intra-abdominal venous thrombosis. Digital ischemia may occur. Easy bruising,epistaxis,or GI hemorrhage may be observed. Hyperuricemia with secondary gout and uric acid stone and peptic-ulcer disease may complicate the picture.

Cont: Physical examination: Massive splenomegally is the initial presenting sign. Systolic hypertension.

Diagnosis: 1-Always make sure to get previous CBC to know the duration of the problem. 2-Assess the red cell mass. 3- Erythropoietin level is suppressed. 4-Other laboratory test are;red cell count,mean corpuscular volume, red cell distribution width. 5-Increase leukocyte alkaline phosphatase (LAP-score). 6-Bone marrow aspirate and biopsy will provide no specific diagnostic information.

complication {The major complication come from increase in blood viscosity ,over production of RBC,and the attendant increase in uric acid and histamine production.} Sudden increase in splenic size lead to splenic infarction or progressive cachexia. May transforms to myelofibrosis or fibrous metaplasia. Erythromelalgia. Increase incidence of intravascular thrombosis.

Treatment: It is generally an indolent disorder. The main goal of treatment is to keep Hb 14 for men and 12 for women. Periodic phlebotomy. For symptomatic patient you ma try hydroxyurea or interferon. Splenectom. Allogenic bone marrow transplant .

Idiopathic Myelofibrosis:

Introduction: Other designations (angogenic myeloid metaplasia,myelofibrosis with myeloid metaplasia). Is a clonal disorder of hematopoeitc progenitor cell of unknown etiology characterize by marrow fibrosis,myeloid metaplasia ,with extramedullary hematopoiesis and splenomegally. There is over production of collagen 111.

Etiology: The etiology is unknown. No specific cytogenitc abnormality has been identified.

Clinical features: No specific sign or symptoms. Most patients are asympotomatic at presentation &usually recognized by splenic enlargement and/or abnormal blood count . Blood smear revels the characteristic feature of extramedullary hematopiesis. Mild hepatomegally. LDH&Alkaline phosphatase can be high. BM aspirate will give dry tape.

Diagnosis: The diagnosis is by exclusion. Peripheral blood film (teardrop-shaped red cells,nucleated red cells,myelocytes,and promyelocytes) establishes the presence of extramedullary hematopoeisis. Bone marrow is usually not aspirable due to increase marrow reticulin. Marrow biopsy:hyper cellular marrow,with trilineage hyperplasia&in particular megakaryocytes.

Complication: Chronic disease of a median survival of 5years. The patients are prone to deep-seated tissue infections particularly of the lung. Can transform to accelerated phase with constitutional symptoms and marrow failure. In 10% of patients the disorder terminates in a rapidly progressive form of acute leukemia for which therapy is usually is ineffective.

Treatment: There is no specific therapy. Anemia. Splenectomy. Allopurinol. Hydroxyurea.

Essential thrombocytosis:

Essential thrombocytosis: Is a clonal disorder of unknown etiology. Over production of platelets in the absence of definable reason. It can occur at any age group. Unexplained female predominance.

Clinical feature &diagnosis: Symptoms: No specific symptoms . These patients have hemorrhagic& thrombotic tendency.(easy bruising,microvascular occlusion,). Physical examination : usually unremarkable except for the presence of mild splenomegally. Lab investigation: Anemia is unusual. Mild leukocytosis. Blood smear:most remarkable for the number of platelets. Leukocyte alkaline phosphatase is either normal or.

Cont: Hyperkalemia.(Release of platelet K+ with clotting of the blood). Normal PT&PTT( so why bruising?..). Abnormalities of platelets function(bleeding time,abnormal platelet aggregation). Bone marrow biopsy usually reveals both megakaryocyte hyperplasia&hypertrophy with bone marrow cellularity.

Complication: Very high platelet counts are associated primarily with hemorrhage. Platelet counts <a million are more often associated with thrombosis. From the neurological problems migraine-related is the commonest(respond to platelet lowering).,Erythromelalgia (respond to cyclooxygenase inhibitors).

Treatment:  Platelet in asymptotic patient requires no therapy. Hydroxyurea.Vs recombinant  interferon. Aminocaporic acid useful for thrombocytosis associated bleeding. Other symptomatic treatment .