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Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia
Authors: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
Affiliation:1.Department of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, Taiwan;2.Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan;3.School of Law, National Yang Ming Chiao Tung University, Hsinchu City 30093, Taiwan;4.Department of Chemistry, Tamkang University, Tamsui, New Taipei City 251301, Taiwan;5.Department of Pharmacy, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, Taiwan
Abstract: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 SAMD9L mutations). Each patient with SAMD9L mutation also carried an AA-related rare BCORL1 variant or CTLA4 p.T17A GG genotype, respectively, and both presented short telomere lengths. Six of the ten patients analyzed harbored AA-risky HLA 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 SAMD9L-inherited subtype, are immune-mediated and the modified PTCy-based regimen we present is efficient and safe for salvage.
Keywords:anti-thymocyte globulin   nonmyeloablative haploidentical peripheral blood stem cell transplantation   post-transplantation cyclophosphamide   SAMD9L variant   severe aplastic anemia
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