Current Status of Treatment for Chronic Myelogenous Leukemia

Kathryn S. Kolibaba, MD, Brian J. Druker, MD

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Philadelphia Chromosome-Negative CML

Approximately 10% of patients with a clinical and morphologic presentation consistent with CML are found not to have the Philadelphia chromosome on cytogenetic analysis. About half of these patients will have evidence of the BCR-ABL rearrangement, as noted above. Ph-negative, BCR-ABL-negative patients in general are older and more often have thrombocytopenia, lower white blood cell counts, greater monocytosis, lower bone marrow myeloid:erythroid ratio, and less basophilia than BCR-ABL-positive patients.[21,27,28] Patients in this BCR-ABL-negative group probably have a variety of hematologic disorders, including chronic myelomonocytic leukemia (CMML), as well as true BCR-ABL-negative, Ph-negative CML.[21,29] The BCR-ABL-negative, Ph-negative CML patient population is reported to have a low risk for blastic transformation, approximately 25%-50%.[4,30] However, the median survival of these patients is significantly shorter than that of patients with BCR-ABL-positive CML.[28] The natural history of BCR-ABL-negative CML is characterized by progressive leukemic burden, extramedullary leukemic infiltrates, poor response to chemotherapy, and bone marrow failure.[27,31]

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