Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study
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, Robert Arceci, Jorge Braier, Maarten Egeler, Nicole Grois, Ken McClain, Milen Minkov, Carlos Rodriguez-Galindo, Kimo Stine, Takamato, Stefaan Van Gool, Kevin Windebank, Jim Whitlock, 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, Robert Arceci, Jorge Braier, Maarten Egeler, Nicole Grois, Ken McClain, Milen Minkov, Carlos Rodriguez-Galindo, Kimo Stine, Takamato, Stefaan Van Gool, Kevin Windebank, Jim Whitlock
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.
© 2015 by The American Society of Hematology.
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Source: PubMed