The effect of interleukin 11 on thrombocytopenia associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia

Cancer. 2008 Sep 15;113(6):1338-43. doi: 10.1002/cncr.23718.

Abstract

Background: During therapy with tyrosine kinase inhibitors (TKIs), approximately 20% to 50% of patients with chronic myeloid leukemia (CML) develop grade >or=3 thrombocytopenia leading to treatment interruptions and dose reductions. Interleukin 11 (IL-11) reduces the incidence and the severity of thrombocytopenia in solid tumors.

Methods: The authors investigated the efficacy and safety of low-dose IL-11 for improving thrombocytopenia associated with TKI therapy in 14 patients with CML. The starting dose of IL-11 was 10 microg/kg 3 times weekly, and the dose was escalated by 1 dose level every 2 weeks if the patients had no sustained platelet increase.

Results: The median patient age was 52 years. The median platelet count at the time IL-11 was started was 37 x 10(9)/L. All patients had prior TKI dose reductions. After the initiation of IL-11, 8 of 14 patients (57%) had an increase in platelet count with a median peak platelet count of 110 x 10(9)/L. One additional patient had no platelet increase but was able to tolerate an imatinib dose increase. Eleven patients had a decrease in the number of days of TKI therapy interruption secondary to thrombocytopenia after the initiation of IL-11 (6% of total treatment time vs 34% of total treatment time before IL-11). Therapy was well tolerated.

Conclusions: The current results indicated that IL-11 may correct thrombocytopenia associated with TKI therapy for patients with CML and that it has a favorable toxicity profile.

MeSH terms

  • Adult
  • Aged
  • Benzamides
  • Drug Resistance, Neoplasm*
  • Humans
  • Imatinib Mesylate
  • Interleukin-11 / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Middle Aged
  • Pilot Projects
  • Piperazines / adverse effects*
  • Platelet Count
  • Protein Kinase Inhibitors / adverse effects*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / adverse effects*
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / drug therapy*
  • Treatment Outcome

Substances

  • Benzamides
  • Interleukin-11
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases