HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma

BackgroundDespite advances in the treatment of multiple myeloma, a proportion of patients still hardly achieve desired prognosis. Although microtransplant (MST) has proved promising results in treating several hematological malignancies, it has not been studied in multiple myeloma.MethodsWe performe...

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Main Authors: Yangyang Lei, Bo Cai, Zhiqing Liu, Anli Xie, Jianhui Qiao, Yi Wang, Xinrui Chen, Fei Peng, Yingxin Zhao, Jiaxin Chen, Wei Guan, Changlin Yu, Xiao Lou, Kaixun Hu, Ang Zhang, Qiyun Sun, Yajing Huang, Huisheng Ai, Mei Guo
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1509588/full
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author Yangyang Lei
Yangyang Lei
Bo Cai
Zhiqing Liu
Anli Xie
Jianhui Qiao
Yi Wang
Xinrui Chen
Fei Peng
Yingxin Zhao
Jiaxin Chen
Wei Guan
Changlin Yu
Xiao Lou
Kaixun Hu
Ang Zhang
Qiyun Sun
Yajing Huang
Yajing Huang
Huisheng Ai
Mei Guo
author_facet Yangyang Lei
Yangyang Lei
Bo Cai
Zhiqing Liu
Anli Xie
Jianhui Qiao
Yi Wang
Xinrui Chen
Fei Peng
Yingxin Zhao
Jiaxin Chen
Wei Guan
Changlin Yu
Xiao Lou
Kaixun Hu
Ang Zhang
Qiyun Sun
Yajing Huang
Yajing Huang
Huisheng Ai
Mei Guo
author_sort Yangyang Lei
collection DOAJ
description BackgroundDespite advances in the treatment of multiple myeloma, a proportion of patients still hardly achieve desired prognosis. Although microtransplant (MST) has proved promising results in treating several hematological malignancies, it has not been studied in multiple myeloma.MethodsWe performed a retrospective analysis of multiple myeloma patients treated with MST at our institution. Their clinical information and outcome measurements were collected. Furthermore, the fluctuation of donor microchimerism after MST, as well as the alteration of immune function before and after MST were analyzed.ResultsTwenty patients receiving MST were enrolled from June 2008, to May 2024, with an overall response rate of 17/20. The 6-year overall survival (OS) and progression-free survival (PFS) rates were 64.7% and 35.3%, respectively, with no graft-versus-host disease or non-relapse mortality. Incidence of controlled fever and Grade I cytokine release syndrome (CRS) was 40.8%. The OS were comparable between groups with age, International Staging System stage, and Mayo Stratification of Myeloma and Risk-Adapted Therapy stage. However, earlier Durie-Salmon stage, disease in VGPR or CR status prior to MST, and an increase in total cycle number of MST were significantly associated with longer OS. Donor microchimerism was detected in all available peripheral blood samples from 14 days to 6 months post-MST. Furthermore, MST resulted in increased proportions of total CD3+ T cells, and CD4+CD8- T cells in peripheral blood, as well as improved CD4:CD8 ratio and increased proportions of Th0 cells.ConclusionMST extended PFS and OS, and benefit immune reconstitution in multiple myeloma patients. Therefore, MST is a promising treatment for multiple myeloma, especially those with high-risk cytogenetics.
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spelling doaj-art-1ea6e5760cb04a3eb9d92eb6419576a42025-08-20T01:51:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15095881509588HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myelomaYangyang Lei0Yangyang Lei1Bo Cai2Zhiqing Liu3Anli Xie4Jianhui Qiao5Yi Wang6Xinrui Chen7Fei Peng8Yingxin Zhao9Jiaxin Chen10Wei Guan11Changlin Yu12Xiao Lou13Kaixun Hu14Ang Zhang15Qiyun Sun16Yajing Huang17Yajing Huang18Huisheng Ai19Mei Guo20Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaChinese PLA Medical School, Chinese PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaChinese PLA Medical School, Chinese PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Hematology, Strategic Support Force Medical Center, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Hematology, Innovvy for Biotechnology Experiments Center, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaSenior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, ChinaBackgroundDespite advances in the treatment of multiple myeloma, a proportion of patients still hardly achieve desired prognosis. Although microtransplant (MST) has proved promising results in treating several hematological malignancies, it has not been studied in multiple myeloma.MethodsWe performed a retrospective analysis of multiple myeloma patients treated with MST at our institution. Their clinical information and outcome measurements were collected. Furthermore, the fluctuation of donor microchimerism after MST, as well as the alteration of immune function before and after MST were analyzed.ResultsTwenty patients receiving MST were enrolled from June 2008, to May 2024, with an overall response rate of 17/20. The 6-year overall survival (OS) and progression-free survival (PFS) rates were 64.7% and 35.3%, respectively, with no graft-versus-host disease or non-relapse mortality. Incidence of controlled fever and Grade I cytokine release syndrome (CRS) was 40.8%. The OS were comparable between groups with age, International Staging System stage, and Mayo Stratification of Myeloma and Risk-Adapted Therapy stage. However, earlier Durie-Salmon stage, disease in VGPR or CR status prior to MST, and an increase in total cycle number of MST were significantly associated with longer OS. Donor microchimerism was detected in all available peripheral blood samples from 14 days to 6 months post-MST. Furthermore, MST resulted in increased proportions of total CD3+ T cells, and CD4+CD8- T cells in peripheral blood, as well as improved CD4:CD8 ratio and increased proportions of Th0 cells.ConclusionMST extended PFS and OS, and benefit immune reconstitution in multiple myeloma patients. Therefore, MST is a promising treatment for multiple myeloma, especially those with high-risk cytogenetics.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1509588/fullmyelomaimmunotherapiesimmunologymicro-transplantmicrochimerism
spellingShingle Yangyang Lei
Yangyang Lei
Bo Cai
Zhiqing Liu
Anli Xie
Jianhui Qiao
Yi Wang
Xinrui Chen
Fei Peng
Yingxin Zhao
Jiaxin Chen
Wei Guan
Changlin Yu
Xiao Lou
Kaixun Hu
Ang Zhang
Qiyun Sun
Yajing Huang
Yajing Huang
Huisheng Ai
Mei Guo
HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
Frontiers in Immunology
myeloma
immunotherapies
immunology
micro-transplant
microchimerism
title HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
title_full HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
title_fullStr HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
title_full_unstemmed HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
title_short HLA-mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
title_sort hla mismatched stem cell microtransplant prolonged overall survival and promoted immunological reconstitution for multiple myeloma
topic myeloma
immunotherapies
immunology
micro-transplant
microchimerism
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1509588/full
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