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Clinical Crossroads | Clinician's Corner

A 41-Year-Old Woman With Chronic Myelogenous Leukemia

Joseph H. Antin, MD, Discussant
JAMA. 2003;290(8):1083-1090. doi:10.1001/jama.290.8.1083.
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DR BURNS: Mrs P is a 41-year-old woman with chronic myelogenous leukemia (CML). She previously worked as a hairdresser but has not worked for several months. Mrs P lives with her husband and children. She has commercial insurance.

For a number of years, Mrs P noted that she felt fatigued and had headaches. She sought medical care, but no explanation was found. In June 2002, she went to a new primary care physician and was found to have a white blood cell count of 58 × 103/µL, hematocrit of 41.4%, and a platelet count of 211 × 103/µL. There were 51 polys, 2 monocytes, 1 eosinophil, 1 promyelocyte, 13 myelocytes, 14 bands, and 5 metamyelocytes. A bone marrow biopsy was performed and she was found to have a myeloproliferative disorder; cytogenetic testing showed classic Philadelphia chromosome (Ph).

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Figure 2. Putative Effect of Therapy on Chronic Myelogenous Leukemia (CML) Burden
Graphic Jump Location
Hydroxyurea rarely results in hematologic remissions but controls most manifestations of stable-phase disease. A minority of patients enter hematologic and cytogenetic remission with interferon, but most people still have detectable disease by reverse transcriptase polymerase chain reaction (RT-PCR). Imatinib is more likely to induce remission than interferon or hydroxyurea, but 95% of patients have detectable BCR-ABL by polymerase chain reaction. Stem cell transplantation is known to cure the disease. The conditioning regimen (chemotherapy or chemoradiotherapy administered prior to stem cell infusion) contributes modest cytoreduction, but the bulk of the benefit derives from immunologic control of the disease through a graft-vs-leukemia effect. The number of residual cells that are tantamount to cure of the disease cannot be determined. The arrows indicate that for each therapy, a proportion of patients may have a smaller burden of CML cells. FISH indicates fluorescence in situ hybridization; HSCT, hematopoietic stem cell transplantation.
Figure 1. Production of the BCR-ABL Fusion Gene
Graphic Jump Location
Translocation of a segment of the BCR (breakpoint cluster region) gene from chromosome 22 and the proto-oncogene ABL from chromosome 9 results in the BCR-ABL fusion gene, which is required for leukemic transformation.

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