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Dynamics and management of cytopenias associated with dasatinib therapy in patients with chronic myeloid leukemia in chronic phase after imatinib failure
Authors:Alfonso Quintás‐Cardama MD  Fabio Pires De Souza Santos MD  Hagop Kantarjian MD  Susan O'Brien MD  Stefan Faderl MD  Ahmed Awais MD  Gautam Borthakur MD  Jorge Cortes MD
Affiliation:1. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;2. Department of Internal Medicine, Memorial Hermann Hospital, The University of Texas, Houston, Texas;3. Fax: (713) 794‐4297
Abstract:

BACKGROUND:

The incidence, dynamics, and management of cytopenias were investigated in patients with chronic myeloid leukemia in chronic phase (CP CML) who received dasatinib therapy after imatinib failure.

METHODS:

Data were analyzed from 130 patients with CP CML who were treated with dasatinib from November 2003 to March 2006 in phase 1 (n = 22) or phase 2 or 3 (n = 108) studies for the development of grade 2 to 4 cytopenia (according to the National Cancer Institute Common Terminology Criteria [version 3.0]).

RESULTS:

Grade 2 to 4 neutropenia and/or thrombocytopenia occurred in 94 (72%) patients during dasatinib therapy and grade 3 to 4 occurred in 67 (52%) patients. Of the 94 patients who developed grade 2 to 4 neutropenia and/or thrombocytopenia, 64 (68%) also developed at least grade 2 anemia, and 16 (17%) developed grade 3 to 4 anemia. Management of cytopenias included transient dasatinib interruption in 35 (37%) patients, filgrastim in 12 (14%) patients, recombinant erythropoietin in 29 (45%) patients, and interleukin‐11 in 3 (5%) patients. Factors associated with an increased risk for developing grade 2 to 4 cytopenias were longer time from diagnosis to treatment, prior interferon or imatinib therapy, and a lower white blood cell count at the initiation of dasatinib therapy.

CONCLUSIONS:

Hematologic toxicity was frequent during dasatinib therapy in patients with CP CML, particularly at doses >100 mg daily. Treatment interruption and/or dose reduction as well as growth factor support were found to be safe and efficacious strategies to facilitate the continuous administration of dasatinib. Cancer 2009. © 2009 American Cancer Society.
Keywords:cytopenias  chronic myeloid leukemia  dasatinib  imatinib  chronic phase  toxicity  treatment interruption
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