Dynamics and management of cytopenias associated with dasatinib therapy in patients with chronic myeloid leukemia in chronic phase after imatinib failure.
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.
Quintás-Cardama
Alfonso
A
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
De Souza Santos
Fabio Pires
FP
Kantarjian
Hagop
H
O'Brien
Susan
S
Faderl
Stefan
S
Awais
Ahmed
A
Borthakur
Gautam
G
Cortes
Jorge
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology; D000069439:Dasatinib; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015994:Incidence; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D019233:Retreatment; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology; D016896:Treatment Outcome
D036341:Intercellular Signaling Peptides and Proteins; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib