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Keywords:

  • absolute neutrophil count;
  • cytogenetic response;
  • imatinib-induced neutropenia;
  • myelosuppression;
  • filgrastim

Abstract

BACKGROUND

Imatinib mesylate administration has become standard treatment for patients with chronic myelogenous leukemia (CML). Although the safety profile of imatinib is favorable, Grade ≥ 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria) occurs in 35–45% of patients with CML in chronic phase who receive standard-dose imatinib. Myelosuppression results in treatment interruptions, which may compromise responses to imatinib. The authors investigated the ability of granulocyte–colony-stimulating factor (filgrastim) to reverse imatinib-associated neutropenia, thereby allowing for more continuous imatinib administration.

METHODS

Thirteen patients with chronic-phase CML and Grade ≥ 3, imatinib-induced neutropenia were treated with filgrastim. Treatment with filgrastim was initiated after a median of 22 months from the start of imatinib. Eleven patients received filgrastim 5 μg/kg 1–3 times weekly, and 2 patients received filgrastim 5 μg/kg daily; doses were titrated to maintain an absolute neutrophil count (ANC) ≥ 109/L.

RESULTS

Seven of 11 patients (64%) who began treatment with an ANC < 1.5 × 109/L had responses (i.e., their ANC improved to ≥ 2 × 109/L within 21 days); the other 4 patients experienced slower recovery but were able to continue receiving imatinib uninterrupted. Before filgrastim administration was initiated, patients did not receive imatinib (due to neutropenia-related treatment interruptions) for an average of 21% of the total time since the start of imatinib. This figure decreased to 6% after the start of filgrastim treatment (P = 0.0008). Before filgrastim treatment was initiated, only one patient had achieved a major (partial) cytogenetic response. After the start of filgrastim treatment, five patients had major cytogenetic responses (including two complete responses).

CONCLUSIONS

The authors concluded that filgrastim may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Some patients may experience improvements in their responses to therapy as a result. Cancer 2004. © 2004 American Cancer Society.