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Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity

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Abstract

Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (n = 10), matched siblings (n = 2), and unrelated bone marrow donors (n = 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4+ T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words)

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Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

APDS:

Activated phosphoinositide 3-kinase delta syndrome

AUC:

Area under the curve

CGD:

Chronic granulomatous disease

CMV:

Cytomegalovirus

EBV:

Epstein-Barr virus

ECOG:

Eastern Cooperative Oncology Group

FCM:

Flow cytometry

FHL:

Familial hemophagocytic lymphohistiocytosis

GVHD:

Graft-versus-host disease

GEFS:

GVHD-free, event-free survival

HCT:

Hematopoietic cell transplantation

HLH:

Hemophagocytic lymphohistiocytosis

IBDS:

Inflammatory bowel disease

IEI:

Inborn errors of immunity

LAD:

Leukocyte adhesion deficiency

KRECs:

Kappa-deleting recombination excision circles

OS:

Overall survival

PCR:

Polymerase chain reaction

PS:

Performance status

RTC:

Reduced-toxicity conditioning

TRECs:

T-cell receptor recombination excision circles

WAS:

Wiskott–Aldrich syndrome

XLP:

X-linked lymphoproliferative syndrome

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Acknowledgements

We thank the staff at the participating hospitals who attended to the patients and provided information for this study. We also thank Eri Watanabe, Naomi Terada, Maki Yamazaki, and Yin Yi for their technical assistance.

Funding

This study was supported by MEXT/JSPS KAKENHI (Grant Number: 22K07887) to HK.

Author information

Authors and Affiliations

  1. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Satoshi Miyamoto, Daiki Niizato, Dan Tomomasa, Akira Nishimura, Takahiro Kamiya, Takeshi Isoda & Tomohiro Morio

  2. Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Akihiro Hoshino & Hirokazu Kanegane

  3. Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Masatoshi Takagi

  4. Center for Transfusion Medicine and Cell Therapy, Tokyo Medical and Dental University Hospital, Tokyo, Japan

    Michiko Kajiwara

  5. Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    Shohei Azumi & Kenichiro Watanabe

  6. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

    Shinsuke Hirabayashi

  7. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan

    Kenichi Sakamoto

  8. Department of Hematology and Oncology, Kobe Children’s Hospital, Hyogo, Japan

    Kenji Kishimoto

  9. Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan

    Takako Miyamura

  10. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Katsutsugu Umeda

  11. Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Kanagawa, Japan

    Ayana Hirose, Dai Keino & Masakatsu Yanagimachi

  12. Department of Pediatrics, Gifu Municipal Hospital, Gifu, Japan

    Kaori Kanda

  13. Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan

    Yuta Sakai & Yasuhiro Ikawa

  14. Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Keisuke Tanaka & Takehiko Mori

  15. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

  16. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Hirotoshi Sakaguchi

Authors
  1. Satoshi Miyamoto
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  2. Daiki Niizato
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  3. Dan Tomomasa
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  4. Akira Nishimura
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  5. Akihiro Hoshino
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  6. Takahiro Kamiya
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  7. Takeshi Isoda
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  8. Masatoshi Takagi
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  9. Michiko Kajiwara
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  10. Shohei Azumi
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  11. Shinsuke Hirabayashi
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  12. Kenichi Sakamoto
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  13. Kenji Kishimoto
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  14. Takako Miyamura
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  15. Katsutsugu Umeda
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  16. Ayana Hirose
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  17. Dai Keino
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  18. Masakatsu Yanagimachi
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  19. Kaori Kanda
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  20. Yuta Sakai
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  21. Yasuhiro Ikawa
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  22. Kenichiro Watanabe
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  23. Keisuke Tanaka
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  28. Hirokazu Kanegane
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Contributions

SM collected and analyzed clinical data and wrote the manuscript. DN, AN, AHo, TK, TI, MK, SA, SH, KS, KKi, TaMi, KU, AHi, DK, MY, KKa, YS, YI, KW, KT, TaMo, and IH recruited the patients and collected the data. DT evaluated post-HCT chimerism using variant-specific ddPCR. MT, HS, and ToMo revised the manuscript. HK conceptualized the study and edited the manuscript. All authors contributed to the study and approved the submitted version.

Corresponding author

Correspondence to Hirokazu Kanegane.

Ethics declarations

Ethical Approval

Informed consent was obtained from the patients and/or their parents. This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics boards of the TMDU (M2022-187).

Consent to Participate/Publication

All participants (and/or their parents) provided written informed consent for the research use of their data and publication.

Conflict of Interest

All authors declare that they have no conflicts of interest to disclose concerning this study.

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Miyamoto, S., Niizato, D., Tomomasa, D. et al. Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity. J Clin Immunol 44, 126 (2024). https://doi.org/10.1007/s10875-024-01734-5

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