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Clinical Trial
. 2015 Sep 17;126(12):1415-23.
doi: 10.1182/blood-2015-03-635151. Epub 2015 Jul 20.

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

Jean Donadieu  1 , Frederic Bernard  2 , Max van Noesel  3 , Mohamed Barkaoui  1 , Odile Bardet  4 , Rosella Mura  5 , Maurizio Arico  6 , Christophe Piguet  7 , Virginie Gandemer  8 , Corinne Armari Alla  9 , Niels Clausen  10 , Eric Jeziorski  2 , Anne Lambilliote  11 , Sheila Weitzman  12 , Jan Inge Henter  13 , Cor Van Den Bos  14 ; Salvage Group of the Histiocyte Society
Collaborators, Affiliations
Clinical Trial

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

Jean Donadieu et al. Blood. .

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.

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Figures

Figure 1
Figure 1
Study flowchart showing decision points after the first 2 therapeutic courses. The cumulative dose of cladribine in this protocol was 120 mg/m2 if the patient had a good response to the initial course.
Figure 2
Figure 2
The response after 2 courses of cladribine/Ara-C. At inclusion, the disease activity was active disease (AD) worse in 23 patients and AD stable in 4 patients. The disease score was similar in AD worse and AD stable patients. After 2 courses, disease activity was nonactive disease, AD stable in 2 patients, and AD better in 23 patients. The median score dropped from 12 at the start of therapy to 3 after 2 courses.
Figure 3
Figure 3
Survival since the start of the protocol (D1 cladribine/Ara-C). (A) Overall survival. (B) Survival according to DAS evolution. Good responders (DAS decrease >4 points) appeared to have a better outcome than poor responders (DAS decrease ≤4 points) (P < .04).
See this image and copyright information in PMC

Comment in

References

    1. Gadner H, Grois N, Arico M, et al. Histiocyte Society. A randomized trial of treatment for multisystem Langerhans’ cell histiocytosis. J Pediatr. 2001;138(5):728–734. - PubMed
    1. Gadner H, Grois N, Pötschger U, et al. Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008;111(5):2556–2562. - PubMed
    1. Gadner H, Minkov M, Grois N, et al. Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121(25):5006–5014. - PubMed
    1. Haupt R, Minkov M, Astigarraga I, et al. Euro Histio Network. Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer. 2013;60(2):175–184. - PMC - PubMed
    1. Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H DAL-HX Study Group. Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Med Pediatr Oncol. 2002;39(6):581–585. - PubMed

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