Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study.

Abstract

An international phase 2 study combining cladribine and cytarabine (Ara-C) was initiated for patients with refractory, risk-organ-positive Langerhans cell histiocytosis (LCH) in 2005. The protocol, comprising at least two 5-day courses of Ara-C (1 g/m(2) per day) plus cladribine (9 mg/m(2) per day) followed by maintenance therapy, was administered to 27 patients (median age at diagnosis, 0.7 years; median follow-up, 5.3 years). At inclusion, all patients were refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all had liver and spleen involvement, and 25 patients had hematologic cytopenia. After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable (n = 2), with an overall response rate of 92%. Median disease activity scores decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001). During maintenance therapy, 4 patients experienced reactivation in risk organs. There were 4 deaths; 2 were related to therapy toxicity and 2 were related to reactivation. All patients experienced severe toxicity, with World Health Organization grade 4 hematologic toxicity and 6 documented severe infections. The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy for refractory multisystem LCH but is associated with high toxicity.

• Authors: Jean Donadieu, Frederic Bernard, Max van Noesel, Mohamed Barkaoui, Odile Bardet, Rosella Mura, Maurizio Arico, Christophe Piguet, Virginie Gandemer, Corinne Armari Alla, Niels Clausen, Eric Jeziorski, Anne Lambilliote, Sheila Weitzman, Jan Inge Henter, Cor Van Den Bos, Salvage Group of the Histiocyte Society
• Journal: Blood (Blood) Vol. 126 Issue 12 Pg. 1415-23 (Sep 17 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 26194764 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• Antineoplastic Agents
• Immunosuppressive Agents
• Cytarabine
• Cladribine
• Vinblastine

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Child, Preschool
• Cladribine (adverse effects, therapeutic use)
• Cytarabine (adverse effects, therapeutic use)
• Female
• Histiocytosis, Langerhans-Cell (diagnosis, drug therapy)
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Infant
• Langerhans Cells (drug effects, pathology)
• Liver (drug effects, pathology)
• Male
• Recurrence
• Spleen (drug effects, pathology)
• Survival Analysis
• Survival Rate
• Vinblastine (therapeutic use)