Introduction To Haematological Malignancies By Tiffany Shaw MBCh

Introduction To Haematological Malignancies By Tiffany Shaw MBCh. B II July 2002

Common Malignancies Acute Chronic Lymphoid • Acute lymphoblastic • Chronic lymphocytic leukemia • Lymphoma • Myeloma Myeloid • Acute myeloid leukemia • Chronic myeloid leukemia

Acute Leukemias -- Definition A malignant disorder in which haemopoietic blast cells proliferate and constitute > 30% of the bone marrow. Lymphoblasts Lymphoblastic leukemia Myeloblasts Myeloid leukemia

Acute Leukemias -- PC 1. 2. 3. 4. 5. 6. 7. 8. Bone marrow infiltrated by blasts cells Bone marrow failure Pan-cytopenia Anaemia fatigue, SOB on exersion Thrombocytopenia bleeding / DIC Neutropenia infections Constitutional symptoms (malaise, anorexia, night sweat, fever) Lymphadenopathy, hepatospenomegaly

Acute Leukemias -- Ix 1. Low Hb 2. Low platelets 3. High WCC (increased blast cells) 4. Low neutrophils 5. Elevated serum uric acid 6. Bone marrow biopsy: infiltration by blast cells

Acute Leukemias – Risk Factors Familial Down’s syndrome Viral infection (EBV Burkitt’s) Radiation Chemotherapy

Acute Leukemias – AML VS ALL AML Myeloblastic Any age 1/3 transformation from other myeloproliferative disorders Increased DIC ALL Lymphoblastic Commonly children Primary event More lymphadenopathy and hepatosplenomegaly

Acute Leukemias -Classification French-American-British Classification Morphology Cytochemistry Immunophenotype Cytogenetics DNA analysis

Examples AML Promyelocytic Myelomonocytic Monocytic Erythroid Megakeryoblastic Undifferentiated …. ect. ALL Small cells Large cells Vacuolated basophillic blast cells

Acute Leukemias -- Mx Supportive Rx Anaemia: blood transfusion prn Bleeding: platelets prn Infection: antibiotics prn Social support + issues

Acute Leukemias -- Mx Chemotherapy: Remission-induction phase Consolidation phase Maintenance phase (for ALL) prednisone, daunorubicin, vincristine, thioguanine, cyclophosphamide…

Acute Leukemias -- Mx Bone Marrow Transplantation: High-dose chemo Rx Removal of stem cells from donor Transplantation into recipient

Acute Leukemias -- Prognosis AML ~ 30 -40% cured Varies widely with age, comorbidity. . etc. ALL In children, ~ 70% cured In adults, ~ 30 -40%

Chronic Myeloid Leukemia Increase in neutrophils and their precursors Really a myeloproliferative disorder > 95% patients have chromosomal mutation --- Philadelphia chromosome

CML -- PC Constitutional symptoms (anorexia, weight loss, fatigue, night sweat) Splenomegaly (hypochondrial pain) Asymptomatic – incidental finding

CML -- Ix Increased WCC (neutrophils and precursors) Later bone marrow failure (anaemia + thrombocytopenia) Raised serum B 12 Raised serum uric acid Bone marrow biopsy hypercellular with high myeloid: erythroid ratio

CML – Course/Progression Chronic Phase 1. Raised WCC 2. Constitutional symptoms / Asymptomatic Accelerated Phase 1. Anaemia + thrombocytopenia 2. Splenomegaly 3. Bone marrow fibrosis Acute Phase 1. Transformation to acute leukemia (80% AML, 20% ALL)

CML -- Mx Chronic Phase Hydroxyurea Interferons Chemo Rx Bone marrow transplantation Acute Phase Same as acute leukemia

Chronic Lymphcytic Leukemia Increased lymphocytes (B cells) in the blood, bone marrow, lymph nodes, and spleen. Lymphoproliferative disorder

CLL -- PC Asymptomatic Lymphadenopathy Constitutional symptoms (night sweat, weight loss, anorexia) Symptoms of bone marrow failure Splenomagaly

CLL -- Ix Lymphocytosis (B cells) Low serum Ig Raised serum uric acid Bone marrow biopsy lymphocytic infiltration

CLL -- Ix Depends on stage: Stage A B C • < 3 lymph node • > 3 lymph node • Bloods groups involvement • Bloods normal abnormal (anaemia + thrombocyto penia)

CLL -- Mx 1. Observation (stage A) 2. Chlorambucil PO (lower lymphocyte 3. 4. 5. 6. count and lymphadenopathy) Corticosteroid Fludarabine IV Other chemo Rx Supportive care

CLL -- Prognosis Variable May remain stationary or progress Some stay asymptomatic for > 10 years Cause of death = bone marrow failure, infiltration of other organs