Cladribine with immediate rituximab for the treatment of patients with variant hairy cell leukemia.

In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, patients with HCLv were treated with simultaneous cladribine and rituximab.
Patients with HCLv with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1 to 5, with eight weekly doses of rituximab 375 mg/m(2) beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry.
By 6 months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported cases treated with cladribine alone (P < 0.0001). Of the 9 CRs, 8 remain free of MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major infections.
Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer.
AuthorsRobert J Kreitman, Wyndham Wilson, Katherine R Calvo, Evgeny Arons, Laura Roth, Jeffrey Sapolsky, Hong Zhou, Mark Raffeld, Maryalice Stetler-Stevenson
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 24 Pg. 6873-81 (Dec 15 2013) ISSN: 1078-0432 [Print] United States
PMID24277451 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Copyright©2013 AACR.
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin Heavy Chains
  • Cladribine
  • Rituximab
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal (administration & dosage)
  • Antibodies, Monoclonal, Murine-Derived (administration & dosage)
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
  • Cladribine (administration & dosage)
  • Female
  • Humans
  • Immunoglobulin Heavy Chains (genetics)
  • Leukemia, Hairy Cell (drug therapy, pathology)
  • Male
  • Middle Aged
  • Remission Induction
  • Rituximab
  • Treatment Outcome

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