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CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Phase 2 study using low dose cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis

Leukemia volume 38, pages 803–809 (2024)Cite this article

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Abstract

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18–66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456–9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126–7.874) as poor prognostic factors for EFS. The most common grade 3–4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.

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Fig. 1: Muational profiles from 43 LCH patients.
Fig. 2: Study diagram of 61 LCH patients.
Fig. 3: OS and EFS of 61 LCH patients.

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Data availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the patients and their families for their trust, respect and support. They also acknowledge all clinicians for their help in accomplishing this work.

Funding

This study was supported by the National Key Research and Development Program of China (2022YFC2705003), Beijing Natural Science Haidian frontier Foundation (L222081), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-A-193).

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Author notes

  1. These authors contributed equally: Long Chang, Min Lang.

Authors and Affiliations

  1. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Long Chang, Min Lang, He Lin, Hao Cai, Ming-Hui Duan, Dao-Bin Zhou & Xin-Xin Cao

  2. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China

    Long Chang, Min Lang, He Lin, Hao Cai, Ming-Hui Duan, Dao-Bin Zhou & Xin-Xin Cao

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Contributions

LC and ML contributed to data analysis and patient follow-up; MHD and DBZ retrospectively reviewed patient records and contributed to data collection; LC, ML, and XXC wrote the paper; and all authors revised the paper and approved the submitted version.

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Correspondence to Xin-Xin Cao.

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The author declares no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all patients included in the study.

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Consent for publication was obtained from all patients included in the study.

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Chang, L., Lang, M., Lin, H. et al. Phase 2 study using low dose cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis. Leukemia 38, 803–809 (2024). https://doi.org/10.1038/s41375-024-02174-1

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