Chromosomal Aberrations during Interferon Therapy for Chronic Myelogenous Leukemia

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Abstract
Interferon treatment of chronic myelogenous leukemia can lead to hematologic as well as cytogenetic remissions.1 2 3 4 5 We report cytogenetic data for 44 patients with chronic myelogenous leukemia who were treated with interferon alfa-2b. Eight of these patients had a partial cytogenetic remission, and three patients had a complete cytogenetic remission, confirming well-established results. We also noted a new phenomenon: 7 of the 44 patients (16 percent) had chromosomal abnormalities in addition to the Philadelphia (Ph) translocation before therapy, and 10 (23 percent) were found to have other abnormalities during therapy with interferon ( Table 1 ). As compared with the cytogenetic findings in 120 Ph-positive patients with chronic myelogenous leukemia, among whom additional chromosomal abnormalities developed in 27 (22 percent) during conventional therapy with busulfan or hydroxyurea, the time of onset and the type of chromosomal abnormalities were different in the interferon-treated patients. Whereas additional chromosomal abnormalities developed in 18 percent of the patients treated with interferon during the chronic phase, only 8 percent of those who received conventional treatment had new chromosomal abnormalities during this period. Furthermore, in the interferon group, the additional anomalies affected chromosomes that are usually not involved in chronic myelogenous leukemia. Two patients, for example, had translocations between chromosomes 2 and 15, in addition to (9;22) translocations. In four patients the short arm of chromosome 7 was partially or totally deleted. In contrast, none of the 120 conventionally treated patients had rearrangements between chromosomes 2 and 15, and none had a deletion of 7p. An isochromosome of the long arm of chromosome 17 is a characteristic aberration in chronic myelogenous leukemia, generally presaging rapid aggravation of the disease.6 7 8 9 During interferon treatment, other aberrations of chromosome 17 were found in patients during chronic phases lasting 6, 15, and 21 months. Although the role and importance of most of these anomalies are not known, the loss of 7p material was an unfavorable prognostic factor, since all four patients had rapid progression of the disease after detection of the anomaly.