Immune thrombocytopenia in patients with chronic lymphocytic leukemia treated with cladribine-based regiments or chlorambucil--follow-up of PALG-CLL randomized trials

Eur J Haematol. 2013 Jul;91(1):1-9. doi: 10.1111/ejh.12112. Epub 2013 Apr 19.

Abstract

Objectives: The relationship between treatments of chronic lymphocytic leukemia (CLL) with cladribine (2-CdA) or chlorambucil and immune thrombocytopenia (IT) has not been yet determined.

Methods: The records of 777 patients in two randomized Polish Adult Leukemia Group (PALG)-CLL programs treated with these agents were retrospectively analyzed.

Results: Immune thrombocytopenia occurred in 55 of 777 (7.1%) patients. No significant differences in IT prevalence were seen between patients on chlorambucil or 2-CdA-based regiments (P = 0.33). IT developed at a median time of 0.499 yr (0.06-4.8) from the start of CLL therapy. This time was significantly longer in patients treated with chlorambucil (2.03 yr, 95% CI: 0.06-4.22) in relation to patients treated with 2-CdA-based regiments (0.52 yr, 95%CI: 0.34-0.69, P = 0.049). Overall survival (OS) of patients with IT and those without IT were similar (2.65 yr vs. 3.2 yr P = 0.23) but the severity of bleeding was more pronounced in the 2-CdA group. The responses to IT therapy were 35%, 54% and 75% for steroids, chemotherapy and splenectomy, respectively.

Conclusions: In this study, an unexpectedly high percentage of IT incidence was demonstrated in patients with CLL requiring chemotherapy. Although no marked differences were seen in IT frequency in patients treated with 2-CdA-based regiments compared to chlorambucil regimen, the clinical course of hemorrhagic diathesis was more severe in 2-CdA group. Also, the time elapsed from study screening to IT diagnosis was significantly shorter in the 2-CdA group than in the chlorambucil group suggesting a causative relationship. The appearance of IT did not influence the median time of OS.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chlorambucil / therapeutic use*
  • Cladribine / therapeutic use*
  • Female
  • Follow-Up Studies
  • Hemorrhage
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications*
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Male
  • Middle Aged
  • Prevalence
  • Retrospective Studies
  • Thrombocytopenia / complications*
  • Thrombocytopenia / immunology
  • Thrombocytopenia / therapy
  • Time Factors
  • Treatment Outcome

Substances

  • Chlorambucil
  • Cladribine