Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia
Most cases of acquired aplastic anemia (AA) arise from autoimmune destruction of hematopoietic stem and progenitor cells. Human leukocyte antigen (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly app...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15192 |
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| author | Rong-Long Chen Peng Peng Ip Jy-juinn Shaw Yun-Hsin Wang Li-Hua Fan Yi-Ling Shen Nithila A. Joseph Tsen-Erh Chen Liuh-Yow Chen |
| author_facet | Rong-Long Chen Peng Peng Ip Jy-juinn Shaw Yun-Hsin Wang Li-Hua Fan Yi-Ling Shen Nithila A. Joseph Tsen-Erh Chen Liuh-Yow Chen |
| author_sort | Rong-Long Chen |
| collection | DOAJ |
| description | Most cases of acquired aplastic anemia (AA) arise from autoimmune destruction of hematopoietic stem and progenitor cells. Human leukocyte antigen (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly applied to salvage AA using bone marrow as graft and anti-thymocyte globulin (ATG) in conditioning. Herein, we characterize a cohort of twelve AA patients clinically and molecularly, six who possessed other immunological disorders (including two also carrying germline <i>SAMD9L</i> mutations). Each patient with <i>SAMD9L</i> mutation also carried an AA-related rare <i>BCORL1</i> variant or <i>CTLA4</i> p.T17A GG genotype, respectively, and both presented short telomere lengths. Six of the ten patients analyzed harbored AA-risky <i>HLA</i> polymorphisms. All patients recovered upon non-HSCT (n = 4) or HSCT (n = 8) treatments. Six of the eight HSCT-treated patients were subjected to a modified PTCy-based regimen involving freshly prepared peripheral blood stem cells (PBSC) as graft and exclusion of ATG. All patients were engrafted between post-transplantation days +13 and +18 and quickly reverted to normal life, displaying a sustained complete hematologic response and an absence of graft-versus-host disease. These outcomes indicate most AA cases, including of the <i>SAMD9L</i>-inherited subtype, are immune-mediated and the modified PTCy-based regimen we present is efficient and safe for salvage. |
| first_indexed | 2024-03-09T17:44:20Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:20Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3667a687cccb42a28a974dd03edcb6772023-11-24T11:15:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231519210.3390/ijms232315192Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic AnemiaRong-Long Chen0Peng Peng Ip1Jy-juinn Shaw2Yun-Hsin Wang3Li-Hua Fan4Yi-Ling Shen5Nithila A. Joseph6Tsen-Erh Chen7Liuh-Yow Chen8Department of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 115024, TaiwanSchool of Law, National Yang Ming Chiao Tung University, Hsinchu City 30093, TaiwanDepartment of Chemistry, Tamkang University, Tamsui, New Taipei City 251301, TaiwanDepartment of Pharmacy, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 115024, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 115024, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 115024, TaiwanInstitute of Molecular Biology, Academia Sinica, Taipei 115024, TaiwanMost cases of acquired aplastic anemia (AA) arise from autoimmune destruction of hematopoietic stem and progenitor cells. Human leukocyte antigen (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly applied to salvage AA using bone marrow as graft and anti-thymocyte globulin (ATG) in conditioning. Herein, we characterize a cohort of twelve AA patients clinically and molecularly, six who possessed other immunological disorders (including two also carrying germline <i>SAMD9L</i> mutations). Each patient with <i>SAMD9L</i> mutation also carried an AA-related rare <i>BCORL1</i> variant or <i>CTLA4</i> p.T17A GG genotype, respectively, and both presented short telomere lengths. Six of the ten patients analyzed harbored AA-risky <i>HLA</i> polymorphisms. All patients recovered upon non-HSCT (n = 4) or HSCT (n = 8) treatments. Six of the eight HSCT-treated patients were subjected to a modified PTCy-based regimen involving freshly prepared peripheral blood stem cells (PBSC) as graft and exclusion of ATG. All patients were engrafted between post-transplantation days +13 and +18 and quickly reverted to normal life, displaying a sustained complete hematologic response and an absence of graft-versus-host disease. These outcomes indicate most AA cases, including of the <i>SAMD9L</i>-inherited subtype, are immune-mediated and the modified PTCy-based regimen we present is efficient and safe for salvage.https://www.mdpi.com/1422-0067/23/23/15192anti-thymocyte globulinnonmyeloablative haploidentical peripheral blood stem cell transplantationpost-transplantation cyclophosphamide<i>SAMD9L</i> variantsevere aplastic anemia |
| spellingShingle | Rong-Long Chen Peng Peng Ip Jy-juinn Shaw Yun-Hsin Wang Li-Hua Fan Yi-Ling Shen Nithila A. Joseph Tsen-Erh Chen Liuh-Yow Chen Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia International Journal of Molecular Sciences anti-thymocyte globulin nonmyeloablative haploidentical peripheral blood stem cell transplantation post-transplantation cyclophosphamide <i>SAMD9L</i> variant severe aplastic anemia |
| title | Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia |
| title_full | Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia |
| title_fullStr | Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia |
| title_full_unstemmed | Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia |
| title_short | Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia |
| title_sort | anti thymocyte globulin atg free nonmyeloablative haploidentical pbsct plus post transplantation cyclophosphamide is a safe and efficient treatment approach for pediatric acquired aplastic anemia |
| topic | anti-thymocyte globulin nonmyeloablative haploidentical peripheral blood stem cell transplantation post-transplantation cyclophosphamide <i>SAMD9L</i> variant severe aplastic anemia |
| url | https://www.mdpi.com/1422-0067/23/23/15192 |
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