1. Chronic leukemias أ. م. د. محمد شنين علي العبادي معاون عميد كلية الطب / جامعة كربلاء ورئيس فرع الامراض والطب العدلي M. B. Ch. B. & F. I. C. P.(Hematopathology) الاثنين 2015/4/7 الساعة الحادية عشرة والنصف صباحا

2. Definition and classification of chronic leukemias Definition: Chronic leukemias are malignancies of mature hemopoietic cells. Classification: 1.Chronic myeloid (myelocytic) leukemia (CML). 2.Lymphoproliferative disorders (LPD) which include many forms like Chronic lymphoid (lymphocytic) leukemia (CLL) and others.

3. Classification of LPD 1.Leukemias: A.CLL (Chronic lymphocytic leukemia),(B-CLL and T-CLL). B.PLL (Prolymphocytic leukemia),(B-PLL and T-PLL). C. HCL (Hairy cell leukemia) D. Plasma cell leukemia. 2. Lymphomas: Follicular lymphoma, Mantle cell lymphoma, and splenic lymphoma. 3. Leukemia/lymphoma syndrome. NB: clinically you will see leukemias and lymphomas.

4. B-CLL Represents a B-cell leukemia in which there is a neoplastic proliferation of mature B cells in the bone marrow. Usual age is above 50 yr.

5. B-CLL Pathogenesis The neoplastic B-cells will reach the peripheral blood before infiltrating the whole bone marrow. So that peripheral blood lymphcytosis is diagnostic before the presence of 3P, then lymphocytes go to infiltrate lymph nodes leading to painless symmetrical lymphadenopathy like cervical, axillary and inguinal lymph nodes

6. B-CLL Pathogenesis, continue Then B-cells infiltrate the liver and spleen and may after that cause anemia with or without thrombocytopenia. So that 3P is not a feature of CLL unless the disease is advanced. Immunity is generally low due to low normal lymphocytes.

7. B-CLL Lab.diagnosis MIC features are very important 1.CBC, Blood film. Normal or low Hb, Lymphocytosis >5X10 9 /L with predominently mature looking lymphocytes with large nucleus, condensed nuclear chromattin and scanty cytoplasm, together with frequent smear cells. Platelets are usually normal unless advanced disease which leads to low platelets.

8. 2. Bone marrow aspiration and biopsy The aspirate should show lymphocyte % of at least 40% of the total marrow nucleated cells. By the above morphology, differentiation between B-CLL and lymphoma can be done. Immunophenotyping CD 5 and CD 23 positive B-cells while SmIg (surface membrane immunoglobulin) is weakly Positive.

10. Immunophenotyping is very important when the morphology is unclear for the differentiation between B-CLL and lymphoma since SmIg is strongly positive in lymphoma with negative CD 5 and CD 23 Cytogenetics Defects in chromosomes no.11,12,&13 are found in 50% of cases. Trisomy 12 carries poor prognosis.

11. Please answer by T or F When there is generalized lymphadenopathies with hepatosplenomegaly and peripheral blood lymphocytosis, differential diagnosis will be Lymphoma, CLL, or PLL.

12. B-PLL B-PLL=B-prolymphocytic leukemia Usually in B-CLL, there are few circulating prolymphocytes (less than 10%) which are twice the size of lymphocytes. When the % of such cells is 10%-55% the condition is called CLL/PLL while when they constitute >55% the condition is called PLL.

13. Chronic myeloid leukemia (CML) It is a clonal disorder, resulting from an acquired genetic change in the pluripotential stem cell. All age groups are affected.

14. CML Pathogenesis Acquisition of philadelphia chromosome (chromosome number 22)due to reciprocal translocation t(9;22) is important for the development of CML and at the same time carries good prognosis. Neoplastic proliferation of such pluripotential stem cells leads to increase in myeloid series and platelets and decrease in erythroid series.

15. CML, Lab.diagnosis 1.CBC, b.film Low or normal Hb Very high WBC count, may be more than 100X10 9 /L, with all myeloid series, but mainly neutrphils and myelocytes. Platelets count is usually high (part of the malignant process). 2. Bone marrow is usually important for follow up of marrow fibrosis.

17. Thank you