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Splenic irradiation combined with plasmapheresis and rituximab: a new option reducing donor-specific antibody in haploidentical hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 58, pages 226–228 (2023)Cite this article

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for various malignant and non-malignant hematopoietic diseases [1]. However, human leukocyte antigen (HLA) donor-specific antibodies (DSAs) found in patients before and/or after present a major problem in the producing positive patient outcomes following haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) [2]. Previous studies have shown that pre-existing DSAs in patients before transplantation were associated with graft failure, delayed hematopoietic recovery, and poor graft function [3]. When patients are found to have DSAs, they usually receive desensitization treatment to reduce DSAs, commonly consisting of plasmapheresis, immunoglobulin therapy, and monoclonal antibodies [4]. Sometimes patients do not respond well to desensitization treatment and DSAs persist, especially in patients with high mean fluorescence intensity (MFI) levels of DSAs before treatment [3]. There are some studies suggesting that the spleen is a major source of DSAs during antibody-mediated rejection (AMR) in solid organ transplantation (SOT) [5]. Splenectomy before transplantation may help eliminate the would-be contribution of newly generated DSAs originating from splenic lymphoid tissue, thus improving transplantation outcomes [6]. Since splenectomy has a long recovery time, it is not always a feasible treatment option in patients in need of haplo-HSCT. Thus, splenic irradiation may be an effective alternative treatment which has already been reported in the treatment of kidney transplantation patients with DSAs [7].

To our knowledge, it is currently unknown as to whether splenic irradiation can eliminate pre-existing DSAs before haplo-HSCT. We have conducted a prospective, single-arm study (chictr.org.cn: ChiCTR2100051456) where we combined low-dose splenic irradiation with plasmapheresis and rituximab as a new treatment protocol to reduce DSAs before haplo-HSCT. Our aim is to explore the safety and efficacy of the outlined treatment protocol including splenic irradiation.

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Fig. 1: Change of DSAs at each time point.

Data availability

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

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Acknowledgements

We would like to thank Dr. Jing Li, Dr Silu Liu for the collection of the initial data. We would also like to thank the department of radiotherapy of the first affiliated hospital of Soochow University, which provides the equipment and facilities for radiation therapy for the patients.

Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 82170222, 81974001, and 82073337); the Jiangsu Natural Science Foundation (BK20211070); The Key Disease Program of Suzhou (LCZX202101); National Science and Technology Major Project (2017ZX09304021); National Key R&D Program of China (2019YFC0840604, 2017YFA0104502); Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Jiangsu Medical Outstanding Talents Project (JCRCA2016002); and Jiangsu Provincial Key Research and Development Program (BE2019670); Jiangsu Provincial Key Medical Center (YXZXA2016002).

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Author notes

  1. These authors contributed equally: Shiyuan Zhou, Xiao Ma, Chao Ma.

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China

    Shiyuan Zhou, Xiao Ma, Ling Li, Shijia Li, Jun He, Depei Wu & Xiaojin Wu

  2. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, Jiangsu Province, China

    Shiyuan Zhou, Xiao Ma, Jun He, Depei Wu & Xiaojin Wu

  3. Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    Shiyuan Zhou, Xiao Ma, Jun He, Depei Wu & Xiaojin Wu

  4. Soochow Hopes Hematonosis Hospital, Suzhou, Jiangsu Province, China

    Chao Ma & Qian Zhu

  5. Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, China

    Qi Zhao & Songbing Qin

  6. School of Public Health, Medical College of Soochow University, Suzhou, 215000, Jiangsu Province, China

    Zaixiang Tang

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Contributions

SZ, XM, and CM contributed to the accrual and treatment of patients, data acquisition, interpretation and analysis. DW, XW, and SQ performed the research and designed this study. XW contributed to study concept and protocol development, oversight of study conduct, and data interpretation and analysis. Q Zhu, Q Zhao and ZT contributed to data interpretation and analysis. SZ wrote this paper. All authors drafted and reviewed the manuscript, approved the final version and decided to publish this report, and they all vouch for data accuracy and completeness.

Corresponding authors

Correspondence to Depei Wu, Xiaojin Wu or Songbing Qin.

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The authors declare no competing interests.

Ethics approval and consent to participate

The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of the Medical Ethics Committee of the First Affiliated Hospital of Soochow University. Written informed consent was obtained from individual or guardian participants.

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Zhou, S., Ma, X., Ma, C. et al. Splenic irradiation combined with plasmapheresis and rituximab: a new option reducing donor-specific antibody in haploidentical hematopoietic stem cell transplantation. Bone Marrow Transplant 58, 226–228 (2023). https://doi.org/10.1038/s41409-022-01868-3

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