Does pretreatment fluorescence in situ hybridization for BCR–ABL predict imatinib-associated hematologic toxicity in chronic myeloid leukemia?

Abstract

Imatinib (IM)-associated myelosuppression is rare in gastrointestinal stromal cell tumors (<10%) but common in chronic myeloid leukemia (CML). Selective inhibition of predominantly Philadelphia chromosome (Ph+) driven hematopoiesis may explain myelosuppression in CML. In the absence of clinical methods to quantitate the Ph+/Ph− progenitor ratio, we hypothesized that the pre-IM percentage of BCR–ABL+ cells measured by fluorescence in situ hybridization (FISH) predicts for myelosuppression. FISH analyses performed within 30 days pre-IM 400 mg/day were analyzed in 89 patients with chronic phase CML at three institutions. Patients who developed grade ≥3 cytopenias had a higher percentage of positive FISH (90% vs. 83%; p = 0.02). Cytopenias lasted a median of 16 days, and all patients but one continued IM, achieved complete hematologic and cytogenetic remissions, and did not experience progression, with a follow-up of 61 months. In conclusion, IM-associated cytopenias are associated with a high pre-IM FISH, are reversible, and do not adversely affect outcomes.