The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase.
BACKGROUND
Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression > or = Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown.


METHODS
The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response.


RESULTS
Neutropenia > or = Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia > or = Grade 3 occurred in 31 patients (22%). Any myelosuppression > or = Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade > or = 3 myelosuppression compared with a rate of 75% without Grade > or =3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response.


CONCLUSIONS
Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.
Sneed
Thomas B
TB
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kantarjian
Hagop M
HM
Talpaz
Moshe
M
O'Brien
Susan
S
Rios
Mary Beth
MB
Bekele
B Nebiyou
BN
Zhou
Xian
X
Resta
Debra
D
Wierda
William
W
Faderl
Stefan
S
Giles
Francis
F
Cortes
Jorge E
JE
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D010976:Platelet Count; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate