A Prospective Study for the Treatment of Children With Newly Diagnosed LCH Using a Cytarabine Contained Protocol

Summary

From January 2010 to December 2014, 150 children with MS-LCH were treated in our hospital following a LCH II (Arm B) based protocol. Treatment was based on a modification of the LCH-II (Arm B) based protocol. However, the continuation treatment was extended to 56 weeks and etoposide was omitted from the continuation treatment. For the 59 patients with RO involvement (RO+) (the lungs are not considered a RO in the current study), the rapid response rate (week 6) was 61.0% and the 3-year overall survival (OS) 73.4±5.9%. Rapid responders had a better 3-year survival rate than poor responders (90.9±5.0% vs. 45.7±11.0%, P\<0.001). The 3-year OS in the current study is 10\~20% lower than the rates reported by Gadner et al. and Morimoto et al.. We have not yet adopted effective salvage therapies for RO+ patients with recurrent disease. During the time of this study, cladribine was unavailable. Second-line therapy for non-responders or patients with disease reactivation was individualized treatment based on the physician's experience. An effective salvage therapy is essential for this high-risk group. For 91without RO involvement (RO-), 78 patients (85.7%) were rapid responders at week 6. The 3-year cumulative reactivation rate was 10.7% for RO- patients. No death occurred in this subgroup, with a 3-year OS of 100% in RO- patients. Compared to the LCH II and LCH III trials, the current study had a more intensive initial treatment regimen for RO- patients. However, the addition of etoposide to prednisone and vincristine in the initial therapy did not increase the 6-week response rate for RO- patients (85.7% in this study compared to 83% in the LCH II study and 86% in the LCH III study). Surprisingly, with a relatively intense initial treatment, a relatively low 3-year cumulative reactivation rate was observed in RO- patients in the current study. This result suggests that the initial treatment intensity and duration of continuation therapy both impact disease reactivation. The intensity of induction can affect the degree of disease resolution. Insufficient treatment intensity might lead to late relapse. Similarity to that observed has been in other childhood hematological malignancies. This finding deserves to be tested in prospective clinical trials with long-term follow-up. Cytarabine has been applied for patients with LCH but has never been evaluated in our hospital prospectively. In this study, we administer a cytarabine contained protocol to patients with multisystem involvement with or without risk organs involvement. The treatment results will be compared with our historical studies.

Timeline

Start

2018-07-01

Primary completion

2023-06-30

Completion

2026-06-30

Publications

• Background Simko SJ, McClain KL, Allen CE. Up-front therapy for LCH: is it time to test an alternative to vinblastine/prednisone? Br J Haematol. 2015 Apr;169(2):299-301. doi: 10.1111/bjh.13208. Epub 2014 Nov 16. No abstract available.
• Background Gadner H, Grois N, Potschger U, Minkov M, Arico M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. doi: 10.1182/blood-2007-08-106211. Epub 2007 Dec 18.
• Background Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Potschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. doi: 10.1067/mpd.2001.111331.
• Background Egeler RM, de Kraker J, Voute PA. Cytosine-arabinoside, vincristine, and prednisolone in the treatment of children with disseminated Langerhans cell histiocytosis with organ dysfunction: experience at a single institution. Med Pediatr Oncol. 1993;21(4):265-70. doi: 10.1002/mpo.2950210406.
• Background Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Potschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. doi: 10.1002/pbc.22229.
• Background Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. doi: 10.1182/blood-2015-03-635151. Epub 2015 Jul 20.
• Background Braier J, Rosso D, Pollono D, Rey G, Lagomarsino E, Latella A, Zubizarreta P. Symptomatic bone langerhans cell histiocytosis treated at diagnosis or after reactivation with indomethacin alone. J Pediatr Hematol Oncol. 2014 Jul;36(5):e280-4. doi: 10.1097/MPH.0000000000000165001.
• Background Heritier S, Jehanne M, Leverger G, Emile JF, Alvarez JC, Haroche J, Donadieu J. Vemurafenib Use in an Infant for High-Risk Langerhans Cell Histiocytosis. JAMA Oncol. 2015 Sep;1(6):836-8. doi: 10.1001/jamaoncol.2015.0736. No abstract available.
• Results Gao YJ, Su M, Tang JY, Pan C, Chen J. Treatment Outcome of Children With Multisystem Langerhans Cell Histiocytosis: The Experience of a Single Children's Hospital in Shanghai, China. J Pediatr Hematol Oncol. 2018 Jan;40(1):e9-e12. doi: 10.1097/MPH.0000000000001016.
• Results Su M, Gao YJ, Pan C, Chen J, Tang JY. Outcome of children with Langerhans cell histiocytosis and single-system involvement: A retrospective study at a single center in Shanghai, China. Pediatr Hematol Oncol. 2018 Oct-Nov;35(7-8):385-392. doi: 10.1080/08880018.2018.1545814. Epub 2019 Jan 29.
• Results Gadner H, Minkov M, Grois N, Potschger U, Thiem E, Arico M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. doi: 10.1182/blood-2012-09-455774. Epub 2013 Apr 15.

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