CHRONIC MYELOGENOUS LEUKEMIA (CML)

CML accounts for ~3% of childhood leukemia and include two distinct types-juvenile CML and adult CML. Juvenile CML (Now termed as juvenile myelomonocytic leukemia) presents in younger children lt;5 years of age, more common in those with neurofibromatosis and Noonan syndrome.

Clinically, most cases present with moderate to severe splenohepatomegaly, lymphadenopathy, skin lesions (eczema, xanthoma, cafe au lait spots) and signs of bone marrow failure, e.g. pallor and bleeding.

Pathologically, it is characterized by—(a) leukocytosis with striking monocytosis in peripheral smear, (b) increased cellularity with predominance of immature granulocytes in all stages, specially monocyte precursors in bone marrow, and (c) increased fetal hemoglobin levels.

Nearly all patients have a genetic lesion, with mono­somy 7 in 30%. However, Philadelphia chromosome (d/d adult CML) is absent in these cases.

Treatment of choice is bone marrow transplant, as chemotherapy is not very effective. Even with transplant, 3 year survival rate is 30-50%.

Adult CML is rare in children (3-5% of all CML), characterized by presence of a specific chromosomal translocation, i.e. Philadelphia chromosome (t9;22-q34;11), resulting in presence of a BCR-ABL fusion protein.

Clinically, most pediatric cases present in second decade with a triphasic illness—(a) chronic phase for many years, with failure to thrive and gross splenomegaly, (b) accelerated progression phase, and (c) intermittent or terminal lymphoblastic/myeloblastic crisis.

Pathologically, these cases are characterized by—(a) presence of all types of immature myeloid cells in peripheral smear, (b) myeloid hyperplasia with myeloid blasts and promyelocytes in bone marrow, and (c) presence of Philadelphia chromosome on cytogenetic studies. Thrombocytosis is common.

Treatment during the chronic phase aims to control leukocytosis with Imatinib or other BCR-ABL tyrosine kinase inhibitors as preferred choice, which also retards progression to accelerated phase and reduce the risk of crisis. Acute lymphoid or myeloid crisis is treated with standard ALL or AML therapy. Periodic monitoring with bone marrow every 6 months is advised to assess residual disease or relapse. Bone marrow transplant may be used in non-responders or during accelerated phase.

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