title: 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.
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Lima
authors.forename: Keeran
authors.initials: K
authors.lastname: Sampat
authors.forename: Sarit
authors.initials: S
authors.lastname: Assouline
authors.forename: Debra
authors.initials: D
authors.lastname: Saxe
authors.forename: Sharron
authors.initials: S
authors.lastname: Nault
authors.forename: Mourad
authors.initials: M
authors.lastname: Tighiouart
authors.forename: Morgan
authors.initials: M
authors.lastname: McLemore
authors.forename: Martha
authors.initials: M
authors.lastname: Arellano
authors.forename: Elliott
authors.initials: E
authors.lastname: Winton
authors.forename: Leon
authors.initials: L
authors.lastname: Bernal-Mizrachi
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hanna Jean
authors.initials: HJ
authors.lastname: Khoury
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016374:Oncogene Proteins v-abl / Q000235:genetics; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D016374:Oncogene Proteins v-abl; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D051562:Proto-Oncogene Proteins c-bcr