The combination of methotrexate and cytosine arabinoside in newly diagnosed adult Langerhans cell histiocytosis: a prospective phase II interventional clinical trial

Xiao Han, Mingqi Ouyang, Minghui Duan, Wei Zhang, Tienan Zhu, Jian Li, Shujie Wang, Daobin Zhou, Xiao Han, Mingqi Ouyang, Minghui Duan, Wei Zhang, Tienan Zhu, Jian Li, Shujie Wang, Daobin Zhou

Abstract

Background: Langerhans Cell Histiocytosis (LCH) is a rare disease puzzling both children and adults, however outcome of adult patients is unfavorable. This prospective interventional trial aims to test the efficacy and safety of the combination of methotrexate and cytosine arabinoside in adult LCH patients.

Method: A total of 36 patients enrolled diagnosed with LCH and treated in our center from 1st Jan, 2014 to 30th Jun, 2016.

Result: Nineteen patients underwent the detection of BRAF mutation, with a positive rate of 21.1%. The overall response rate was 100%, only 16.7% achieved complete response. The overall regression rate of osseous lesions was 100%. Regression of central nervous system involvement was also favorable. After a median follow-up of 44 months, the estimated event-free survival was 48.9 months, the overall survival rate was 97.2%. The risk organ involvement showed strong prognostic value, EFS was 34.1 or 54.6 months (p = 0.001) in groups with/without risk organ involvement respectively. Neutropenia and thrombocytopenia were the most common adverse effects.

Conclusion: The regimen of methotrexate and cytosine arabinoside (MA) is effective and safe in treating adult LCH patients, and timely preventions may be considered for the high incidence of hematological adverse effects.

Trial registration: Trial No. NCT02389400 on Clinicaltrials.gov, registered on 10th Mar. 2015.

Keywords: Cytosine arabinoside; Efficacy; Langerhans cell histiocytosis; Methotrexate; Toxicity.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Patient flow in this trial with MA regimen
Fig. 2
Fig. 2
The biopsy site for definitive pathological diagnosis for patients enrolled
Fig. 3
Fig. 3
Survival of adult patients with LCH. a The overall EFS of the entire group in our study. b The overall survival of the entire group in our study. c The EFS of adult patients with and without risk organ involvement. The diamond represents group with risk organ involvement, while the square represents the group without risk organ involvement, including the multi-system disease and single system disease. d The EFS of adult patients with multi-system disease with and without risk organ involvement. The diamond represents MS-RO+ group, while the square represents the MS-RO- group

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