title: Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemia.
abstract: We studied 28 patients with accelerated phase chronic myelogenous leukemia (CML) who were enrolled on the Novartis expanded access study 114. Diagnosis of accelerated phase CML was based on karyotypic evolution (n = 9) and hematologic criteria (n = 18). All patients were begun on 600 mg/day of imatinib mesylate. Dose reductions to 400 mg/day and then 300 mg/day were prescribed for an absolute neutrophil count (ANC) of <0.5/microl or a platelet count of <20,000/microl. Twenty-seven of the 28 patients continued treatment for a median of 34 weeks. Eleven patients developed thrombocytopenia following an average of 8.4 +/- 1.4 weeks of therapy. The onset of thrombocytopenia was associated with disease progression in one patient and a decline in bone marrow megakaryocytes in the other 10. Nine patients recovered to a platelet count of >20,000/microl after an average of 19.7 +/- 1.8 weeks. Patients who developed thrombocytopenia had a longer duration of disease (9.39 vs. 4.35 years; P < 0.01) and were more likely to be diagnosed with accelerated phase CML by hematologic criteria. Hematologic responses in patients with and without thrombocytopenia were comparable; however, 31.3% of patients without thrombocytopenia had a complete cytogenetic response compared to none of those with thrombocytopenia. Grade III-IV thrombocytopenia is common in accelerated phase CML and may be a marker for the inability to achieve cytogenetic response using single agent imatinib mesylate.
authors.affiliation: Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Rm. 3009 Old Clinic Building, Chapel Hill, NC 27599-7305, USA. hvand@med.unc.edu
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: van Deventer
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Hall
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Mitchell
authors.forename: Lee R
authors.initials: LR
authors.lastname: Berkowitz
authors.forename: Cathe
authors.initials: C
authors.lastname: Hogan
authors.forename: Cherie H
authors.initials: CH
authors.lastname: Dunphy
authors.forename: Julie
authors.initials: J
authors.lastname: Koehler
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001549:Benzamides; D002452:Cell Count; D020732:Cytogenetic Analysis; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000068877:Imatinib Mesylate; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008533:Megakaryocytes / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate