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IRZA WAHID
SUBDIVISION OF HEMATOLOGY & MEDICAL ONCOLOGY DEPARTEMENT OF INTERNAL MEDICINE FACULTY OF MEDICINE ANDALAS UNIVERSITY
Leukaemias
eosinophil
Hemocytoblast
BFU-E
erythrocyte
Clonal malignant myeloproliferative disorder (MPD) characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate
Results in increases in myeloid cells, erythroid cells and platelets in peripheral blood and marked myeloid hyperplasia in the bone marrow Originate in a single abnormal haemopoietic stem cell
Introduction- CML
Incidence :1 per 100,000 (UK) Accounts for 7-15% of all leukaemia in adults Median age : 53 years All age groups, including children, can be affected
Introduction- CML
Etiology
Not clear Little evidence of genetic factors linked to the disease Increased incidence
Survivors of the atomic disasters at Nagasaki & Hiroshima Post radiation therapy
Leukaemogenesis
Philadelphia chromosome is an acquired cytogenetic anomaly that is characterizes in all leukaemic cells in CML 90-95% of CML pts have Ph chromosome Reciprocal translocation of chromosome 22 and chromosome 9
Leukaemogenesis
BCR (breakpoint cluster region) gene on chromosome 22 fused to the ABL (Ableson leukemia virus) gene on
chromosome 9 Ph chromosome is found on myeloid, monocytic, erythroid, megakaryocytic, B-cells and sometimes T-cell proof that CML derived from pluripotent stem cell
Leukaemogenesis
Molecular consequence of the t(9;22) is the fusion protein BCRABL, which has increased in tyrosine kinase activity BCR-ABL protein transform hematopoietic cells so that their growth and survival become independent of cytokines It protects hematopoietic cells from programmed cell death (apoptosis)
Clinical Features
Asymptomatic in > 20% Fatigue Bleeding Weight loss Splenic discomfort/fullness (7% present with advanced disease)
Lab features
Lab features
Bone marrow Hypercellular (reduced fat spaces) Myeloid:erythroid ratio 10:1 to 30:1 (N : 2:1) Myelocyte predominant cell, blasts less 10% Megakaryocytes increased & dysplastic Increase reticulin fibrosis in 30-40%
Lab features
Phases
Accelerated phase
Median duration is 3.5 5 yrs before evolving to more aggressive phases Clinical features
Lab features
Increasing splenomegaly refractory to chemo Increasing chemotherapy requirement Blasts>15% in blood Blast & promyelocyte > 30% in blood Basophil 20% in blood Thrombocytopenia Cytogenetic: clonal evolution
Phases
Blastic phase
Resembles acute leukaemia Diagnosis requires > 20% blast in marrow 2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase Survival : 9 mos vs 3 mos (lym vs myeloid)
General Management
Is characterised by the accumulation of nonproliferating mature-appearing lymphocytes in the blood, marrow, lymph nodes, and spleen
In most cases, the cells are monoclonal B lymphocytes that are CD5+
Is the most common form of leukemia in North America and Europe, but is extremely rare in the Orient
Typically occurs in older patients, with the highest incidence being in those aged 50 to 55 years Affects men twice as often as women
Etiology
The cause of CLL is unknown There is increased incidence in farmers, rubber manufacturing workers, asbestos workers, and tire repair workers
Genetic factors have been postulated to play a role in high incidence of CLL in some families
Clinical findings
Approximately 40% of CLL patients are asymptomatic at diagnosis In symptomatic cases the most common complaint is fatigue Less often the initial complaint are enlarged nodes or the development of an infection (bacterial)
Clinical findings
Most symptomatic patients have enlarged lymph nodes (more commonly cervical and supraclavicular) and splenomegaly Hepatomegaly may occure Less common manifestation are infiltration of tonsils, mesenteric or retroperitoneal lymphadenopathy, and skin infiltration Patients rarely present with features of anemia, and bruising or bleeding
Laboratory findings
The blood lymphocyte count above 5,0 G/L In most patients the leukemic cells have the morphologic appearance of normal small lymphocytes In the blood smears are commonly seen ruptured lymphocytes (basket or smudge cells) Careful examination of the blood smear can usually differentiate CLL, and the diagnosis can be confirmed by immunophenotyping
Laboratory findings
the expression of either or light chains on the cell surface membrane the presence of unique idiotypic specificities on the immunoglobulins produced by CLL cells by immunoglobulin gene rearrangements typical B-cell CLL are unique in being CD19+ and CD5+
Hypogammaglobulinemia or agammaglobulinemia are often observed 10 - 25% of patients with CLL develop autoimmune hemolytic anemia, with a positive direct Coombs test The marrow aspirates shows greater than 30% of the nucleated cells as being lymphoid
Differential diagnosis
Infectious causes
bacterial (tuberculosis) viral (mononucleosis)
Malignant causes
B-cell T-cell
leukemic phase of non-Hodgkin lymphomas Hairy-cell leukemia Waldenstrom macroglobulinemia large granular lymphocytic leukemia
Staging
Staging
Prognosis
Rai classification
stage 0 I II III IV median survival (years) >10 > 8 6 2 < 2
stage A B C
Binet classification
Treatment
Alkylating agents (chlorambucil, cyclophosphamide) Nucleoside analogs (cladribine, fludarabine) Monoclonal antibodies Bone marrow transplantation And systemic complications requiring therapy
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