PMID- 32978903 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20220321 IS - 2157-6580 (Electronic) IS - 2157-6564 (Print) IS - 2157-6564 (Linking) VI - 10 IP - 2 DP - 2021 Feb TI - A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients. PG - 291-302 LID - 10.1002/sctm.20-0345 [doi] AB - The clinical applications of human leukocyte antigen (HLA) haploidentical hematopoietic stem cells transplantation (haplo-HSCT) have offered most of the young severe aplastic anemia (SAA) patients an opportunity to accept curative therapy at the early stage of bone marrow lesions. However, the outcome of juvenile SAA patients received haplo-HSCT remain to be improved due to high incidence of graft failure and graft vs host disease (GVHD). Mesenchymal stem cells (MSCs) have been characterized by their hematopoiesis-supporting and immunomodulatory properties. In the current study, we designed a combination of haplo-HSCT with allogenic MSC for treatment of SAA in pediatric and adolescent patients and evaluated its effects. Juvenile patients (<18 years) with SAA (n = 103) were given HLA-haploidentical HSC combined with allogenic MSC after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin and an intensive GVHD prophylaxis, including cyclosporine, short-term methotrexate, mycophenolate mofetil, and basiliximab. Neutrophil engraftment was achieved in 102 of 103 patients in a median time of 14.3 days (range 9-25 days). The median time of platelet engraftment was 25.42 days (range 8-93 days). The cumulative incidence of II-IV acute GVHD at day +100 was 26.32% +/- 0.19% and III-IV acute GVHD was 6.79% +/- 0.06% at day +100, respectively. The cumulative incidence of chronic GVHD was 25.56% +/- 0.26%. The overall survival was 87.15% +/- 3.3% at a median follow-up of 40 (1.3-98) months. Our data suggest that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell may provide an effective and safe treatment for children and adolescents with SAA who lack matched donors. CI - (c) 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press. FAU - Ding, Li AU - Ding L AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. AD - Department of Experimental Hematology & Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China. FAU - Han, Dong-Mei AU - Han DM AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Zheng, Xiao-Li AU - Zheng XL AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Yan, Hong-Min AU - Yan HM AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Xue, Mei AU - Xue M AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Liu, Jing AU - Liu J AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Zhu, Ling AU - Zhu L AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Li, Sheng AU - Li S AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Mao, Ning AU - Mao N AD - Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China. FAU - Guo, Zi-Kuan AU - Guo ZK AD - Department of Experimental Hematology & Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China. AD - Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China. AD - Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China. FAU - Ning, Hong-Mei AU - Ning HM AD - Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China. AD - The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China. FAU - Wang, Heng-Xiang AU - Wang HX AD - Air Force Medical Center, PLA, Beijing, People's Republic of China. FAU - Zhu, Heng AU - Zhu H AUID- ORCID: 0000-0002-8408-3821 AD - Department of Experimental Hematology & Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China. AD - Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China. AD - Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China. AD - Graduate School of Anhui Medical University, Hefei, Anhui, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200925 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 RN - 0 (HLA Antigens) SB - IM MH - Adolescent MH - *Anemia, Aplastic/therapy MH - Child MH - *Graft vs Host Disease MH - HLA Antigens MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - Transplantation Conditioning PMC - PMC7848315 OTO - NOTNLM OT - HLA-haploidentical HSCT OT - bone marrow niche OT - graft vs host disease OT - mesenchymal stem cells OT - pediatric and adolescent patients OT - severe aplastic anemia COIS- The authors declared no potential conflicts of interest. EDAT- 2020/09/27 06:00 MHDA- 2022/03/22 06:00 PMCR- 2020/09/25 CRDT- 2020/09/26 05:32 PHST- 2020/07/25 00:00 [received] PHST- 2020/08/27 00:00 [revised] PHST- 2020/09/12 00:00 [accepted] PHST- 2020/09/27 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2020/09/26 05:32 [entrez] PHST- 2020/09/25 00:00 [pmc-release] AID - SCT312840 [pii] AID - 10.1002/sctm.20-0345 [doi] PST - ppublish SO - Stem Cells Transl Med. 2021 Feb;10(2):291-302. doi: 10.1002/sctm.20-0345. Epub 2020 Sep 25.