بسم ا الرحمن الرحـــــــيم Leukemia Course-Lecture #4
CHRONIC LEUKEMIAS Akram Al-Hilali 2010
08/06/14
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CLASSIFICATION OF CHRONIC LEUKEMIAS Chronic lymphoid is clearly demarcated from chronic myeloid. Morphology, immunophenotyping and gene aberrations are quite distinct. FCM is not done to differentiate the two but is done for CLL. Special cases of chronic myeloid leukemia Special cases of Chronic lymphocytic leukemia. Is there chronic monocytic leukemia?
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SPECIAL “CML” TYPES Chronic
neutrophilic leukemia Chronic eosinophilic leukemia/hypereosinophilic syndrome Atypical chronic myelogenous leukemia (Ph1 negative)
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CHRONIC LYMPHOCYTIC LEUKEMIA Now
classified with the small cell lymphoma as SCLL. Majority are B type Positive for CD5, the T cell marker bone marrow B lymphocytes. Negative for CD10
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CLL
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L
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CLL- Genetic Aberrations
Aberrations were detected in more than 80%. Commonest
are: Deletion 13q14 Deletion 6q21 Trisomy of segment 12q13
Worst survival is in presence of deletion 17p13 (deletion of the tumour-suppressor gene p53). Mutation in the gene for variable region of heavy chain of Ig makes prognosis better than if it is not mutated.
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CHRONIC B CELL NEOPLASMS CELL MARKERS IN THE DIFFERENTIAL DIAGNOSIS OF B CHRONIC LYMPHOID NEOPLASMS Disease
CD19
CD20
CD22
CD23
CD25
CD79a
CD5
CD10
CD11c
CD38
CD56
BCL1
BCL2
BCL6
CD103
CD138
κ/ι
CLL
+
+
-
+
-
-
+
-
-
-/+
-
-
-
-
-
-
+One
FL1
+
+
-
-
-
-
-
+
-
-
-
-
+
+
-
-
+One
MZL2
+
+
+
-
-
+
-
-
-
-
-
-
-
-
-
-
+One
PLL
+
+
+
-
-
+
-/+
-
-
-
-
-
-
-
-
-
+One
MCL3
+
+
-
-
-
-
+
-
-
-
-
+
-
-
-
-
+One
L/P L4
+
+
-
-
-
+
-
-
-
-
-
-
-
-
-
-
+One
DLBCL5
+
+
+
-
-
+
-
-
-
-
-
-
-
-
-
-
+One
HCL
+
+
-
-
+
-
-
-
+
-
-
-
-
-
+
-
+One
Myelom a
-
-/+
+
-
-
-
-
-
-
+
-/+
-
-
-
-
+
+One
1: Follicular Lymphoma 2: Marginal Zone Lymphoma 4. Lymphoplasmacytic cell leukemia 5: Diffuse Large B cell leukemia
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3: Mantle cell leukemia
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OTHER CHRONIC LYMPHOID LEUKEMIAS T-CLL Prolymphocytic
leukemia (PLL) Lymphoplasmacytic lymphoma and Leukemia (Waldenström) Hairy cell leukemia (HCL) Post-transplant Lymphoproliferative disorders (PTLD) 08/06/14
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Myelodysplastic/Myeloproliferative Neoplasms Chronic
myelomonocytic leukemia
(CMML) Atypical Chronic myelogenous leukemia (aCML) Juvenile chronic myelomonocytic leukemia (jCMML)
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CHRONIC MYELOMONOCYTIC LEUKEMIA WHO CRITERIA 1. Persistent peripheral blood monocytosis (>1x109/l) 2. No Philadelphia chromosome or BCRABL fusion gene 3. <20% myeloblasts or monoblasts in the peripheral blood or marrow 4. Evidence of dysplasia in one or more myeloid lineages M:F ratio is 2:1 Leukocytosis. Splenomegaly 08/06/14
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ATYPICAL CML (aCML)- Features
Peripheral blood leukocytosis with increased numbers of mature and immature neutrophils. Prominent dysgranulopoiesis. No Philadelphia chromosome or BCR/ABL fusion gene. Non-specific cytogenetic abnormalities in majority. Neutrophil precursors (e.g., promyelocytes, myelocytes, and metamyelocytes) accounting for more than 10% of white blood cells. Minimal absolute basophilia with basophils accounting for less than 2% of white blood cells. Absolute monocytosis with monocytes typically account for less than 10% of white blood cells. Hypercellular bone marrow with granulocytic proliferation and granulocytic dysplasia. Fewer than 20% blasts in the blood or bone marrow. Thrombocytopenia 08/06/14
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JUVENILE CHRONIC MYELOMONOCYTI (LEUKEMIA (JCMML
Clinical features: hepatosplenomegaly, lymphadenopathy,
pallor, fever and skin rash. M:F ratio is 2:1 Laboratory criteria (all three must be met): 1. Persistent peripheral blood monocytosis (>1 X 10 9/l) 2. No Philadelphia chromosome or BCR–ABL fusion gene 3. <20% myeloblasts or monoblasts in the marrow. Further criteria to be met (need to fulfill at least two): 1. Increased hemoglobin F (corrected for age) 2. Immature myeloid precursors in the peripheral blood smear. 3. Peripheral blood white blood cell count >10X10 9/l 4. Clonal cytogenetic abnormalities (including monosomy 7) 5. GM-CSF hypersensitivity of myeloid progenitors ( in vitro test) In JCMML typically there is dysregulation in the Ras signal transduction pathway
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CMML 08/06/14
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CMML 08/06/14
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MYELODYSPLASTIC SYNDROMES (WHO) Refractory
anemia
– With ringed sideroblasts – Without ringed sideroblasts Refractory
cytopenia with multilineage dysplasia (RCMD). Refractory anemia with excess blasts (RAEB) 5q- syndrome MDS, unclassified. 08/06/14
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MANAGEMENT OF CML Are busulphan days gone? α-Interferon (AIF) Allogeneic HSC transplantation Imatinib mesylate (Glivec)- a kinase inhibitor
specific to the kinase produced by the fused gene produced by the Philadelphia translocation. Imatinib is now approved first-line therapy. Transformed CML 08/06/14
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MANAGEMENT OF CLL May need no therapy, follow up only. ZAP-70 and CD38-19 are important in assessing prognosis. Simple prednisolone-chlorambucil orally. More involved chemotherapy protocols with fludarabine and prednisolone mostly included. Monoclonal immunotherapy for B type (Rituximab), together with aggressive chemotherapy protocols.
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