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

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/m2 per day) plus cladribine (9 mg/m2 per day) foll...

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Veröffentlicht in:Blood 2015-09, Vol.126 (12), p.1415-1423
Hauptverfasser: Donadieu, Jean, Bernard, Frederic, van Noesel, Max, Barkaoui, Mohamed, Bardet, Odile, Mura, Rosella, Arico, Maurizio, Piguet, Christophe, Gandemer, Virginie, Armari Alla, Corinne, Clausen, Niels, Jeziorski, Eric, Lambilliote, Anne, Weitzman, Sheila, Henter, Jan Inge, Van Den Bos, Cor
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Sprache:eng
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Zusammenfassung: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/m2 per day) plus cladribine (9 mg/m2 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. •Patients with LCH, risk organs, refractory to standard VBL-steroid regimen have a poor survival, ∼30%.•In a phase 2 study, with 5 years' median follow-up, cladribine and Ara-C was shown to improve the survival up to 85% for this group.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2015-03-635151