MYELOPROLIFERATIVE DISEASES: Clonal stem cell disorders that lead to uncontrolled hematopoiesis. These related diseases can transform into each other. POLYCYTHEMIA VERA ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS CHRONIC MYELOGENOUS LEUKEMIA

POLYCYTHEMIA VERA Increased red cell mass that is associated with increases in white cell and platelet cnt. Normal red cell mass: F – 23-29 ml/kg M – 26-32 ml/kg

Polycythemia Vera: Pathogenesis Clonal disorder involving stem cell Autonomous proliferation of the erythroid, myeloid & megakaryocytic cell lines. PV progenitor cells are more resistant to apoptosis. Chromosomal abnormality: 20q-, trisomy 8/9 Unknown

PV: Clinical Mx Consequence of hyperviscosity: plethora, poor CNS & coronary circulation Abnormal platelet function: venous thrombosis/ thromboembolism, hemorrhage Increase myeloproliferation: splenomegaly, pruritus (increase histamine release)

PV: Labs Increase Hb & Hct= increase total red cell mass Leucocytosis – granulocytosis Thrombocytosis BM hyperplasia

PV: Diagnostic Criteria Category A: 1. T red cell mass: M > 36 ml/kg F > 32 ml/kg 2. Arterial O2 sat. > 92% 3. Splenomegaly

PV: Dx Category B: 1. Thrombocytosis (PC.> 400T) 2. Leucocytosis (WBC > 12T) 3. Increase LAP score 4. Serum B12 conc. >900 pg/ml Dx: A1+A2+A3 or A1+A2+ any 2 frm B

PV: Complications Erythromelalgia- erythema, warmth, pain “digital infarction” Thrombosis – 15-60% ; MR – 10-40% Hemorrhage – 15-35%; MR – 6-30% Peptic Ulcer disease Pancytopenia & myelofibrosis – “spent phase” – 30-70% Acute leukemic transformation- 1%

PV: Mgt Reduction of Hyperviscosity - phlebotomy ( target Hct- 47%) <50 y.o. – 1 U (450 ml) q other day > 70 y.o. – 250-300 ml TIW + myelosuppressive therapy(hydroxyurea/interferon) erythrocytosis=thrombosis Aspirin/Salicylates – erythromelalgia Splenomegaly

LEUKEMIAS Neoplastic expansion of hematopoietic cells in blood and bone marrow *ACUTE Leukemia- expansion of immature cells * CHRONIC Leukemia- expansion of mature cells Incidence: 4 –5% of cancer among all age group.

AML: Etiology 1. Radiation – genetic damage; immunosuppression 2. Chemicals – benzene 3. Viruses – human T-cell leukemia virus RNA 4. Hereditary influences 5. Non random chromosome abnormalities

AML CLINICAL MANIFESTATION: * Infiltration of organs * granulocytopenia * thrombocytopenia

AML: FAB Classification M1- AML without differentiation M2 – AML with differentiation M3- Acute Promyelocytic Leukemia 50% of cases Chromosomes +8, -5,-7 T(8;21) Multiple AUER RODS FIBRINOLYSIS common T(15:17) / 10% of cases

AML: FAB Classification M4 – Acute Myelomonocytic Leuk M5-Acute Monocytic Leukemia M6-Acute Erythroleukemia (erythremic myelosis) M7 Acute Megakaryocytic Leukemia 15% of cases Frquent extramedullary dss Children/young adults 10% cases Gum,CNS,LN, extramedullary infiltration Long prodromal prd. 5% of cases DRY TAP coz myelofibrosis AML of DOWNs Syndrome

ACUTE LYMPHOCYTIC LEUKEMIA Clonal proliferation of lymphoid progenitor cells originating in the marrow

ALL: FAB Classification SIZE L1- small, uniform CYTPLSM Scanty, basophilia NUCLEUS Regular shape,inscnpcous nucleoli AGE C- 85% A- 31% L2-large, non-uniform variable Irreglr shape, prmnt nucleoi C- 14% A-60% L3- large, uniform Abundant, deep basophilia Reglr shape Promnt nucleoli C- 1% A- 9%

ALL: Classification by IMMUNOPHENOTYPING Early pre-B Pre-B B-cell T-cell

ACUTE LEUKEMIA: Treatment 1. Bone Marrow Transplant a. Allogeneic BMT- 40-45 yrs old with histocompatible sibling ( 50% long term dss free survival) Cx: graft vs. host dss. intestinal pneumonitis Relapse rate: 15-20%

2. Autologous BMT- individuals own marrow for reinfusion * up to 60 yrs. Old * MR: <10% Cx: potential for reinfusion of leukemic cells Long term dss-free survival –50%

ACUTE Leukemia: Treatment 1. Induction Chemotherapy: over all remission rate- 65% 2. Post Remission Therapy: * Consolidation * Maintenance * CNS Prophylaxis Sanctuary Sites: CNS & Testes

Treatment: Supportive Care 1. Antimicrobials: Infection- main threat to absolutely neutropenic pts. High Risk Group: a. prior high dose steroid b. protracted granulocytopenia c. previous fungal sepsis

Acute Leukemia: Treatment 2. Transfusion therapy - component therapy: pRBC, platelet concentrate 3. Hematopoietic growth factors

ALL: Treatment Complications 1. DIC – common in APL – cells lyse & release of thrombogenic materials 2. Hyperleukocytic leukemia- leukostasis 3. Meningeal Leukemia- ALL & Monocytic variant AML 4. Tumor Lysis Syndrome a. hypocalcemia b. hyperkalemia c. hyperphosphatemia d. hyperuricemia e. increasre crea, BUN; LDH

Prognostic Factors in Childhood ALL PARAMETER GOOD POOR White cell cnt Low (<50T) High Age Young (1-10) Oldr (>10) CALLA presnt absnt Lymp cell type Early B cell T cell Cytogenetics normal abnormal FAB class L1 L2