Infusion of haploidentical hematopoietic stem cells combined with mesenchymal stem cells for treatment of severe aplastic anemia in adult patients yields curative effects |
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| Institution: | 1. Air Force Medical Center, People''s Liberation Army, Beijing, People''s Republic of China;2. Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People''s Republic of China;3. Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People''s Republic of China;4. Beijing Institute of Basic Medical Sciences, Beijing, People''s Republic of China;5. The Fifth Medical Center of Chinese People''s Liberation Army General Hospital, Beijing, People''s Republic of China;6. Graduate School of Anhui Medical University, Hefei, People''s Republic of China;1. Daxing Research Institute, University of Science and Technology Beijing, Beijing, China;2. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China;1. Stem Cell Research Centre, Government Stanley Hospital, Chennai, India;2. Stem Cell and Molecular Biology Lab, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India;3. Government Medical College Hospital, Karur, India;4. Hepato-Pancreato Biliary Centre for Surgery and Transplantation, MIOT International Hospital, Chennai, India;1. Department of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha, China;2. Department of Preparations, The First Hospital of Hunan University of Chinese Medicine, Changsha, China;1. Cancer and Blood Disease Institute, Children''s Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;2. Center for Cancer and Blood Disorders, Children''s National Hospital, George Washington School of Medicine, Washington, DC, USA;3. Department of Immunology and Microbiology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA;4. Seattle Children''s Therapeutics, Seattle Children''s Research Institute, Seattle, Washington, USA;1. Institute for Translational Medicine, The Affiliated Hospital, College of Medicine, Qingdao University, Qingdao, China;2. School of Basic Medical Sciences, College of Medicine, Qingdao University, Qingdao, China |
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| Abstract: | Background aimsDespite the great advances in immunosuppressive therapy for severe aplastic anemia (SAA), most patients are not completely cured. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been recommended as an alternative treatment in adult SAA patients. However, haplo-HSCT presents a higher incidence of graft failure and graft-versus-host disease (GVHD). The authors designed a combination of haplo-HSCT and umbilical cord-derived mesenchymal stem cells (UC-MSCs) for treatment of SAA in adult patients and evaluated its effects.MethodsAdult patients (≥18 years) with SAA (N = 25) were given HLA-haploidentical hematopoietic stem cells (HSCs) combined with UC-MSCs after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin and intensive GVHD prophylaxis, including cyclosporine, basiliximab, mycophenolate mofetil and short-term methotrexate. Additionally, the effects of the protocol in adult SSA patients were compared with those observed in juvenile SAA patients (N = 75).ResultsAll patients achieved myeloid engraftment after haplo-HSCT at a median of 16.12 days (range, 11–26). The median time of platelet engraftment was 28.30 days (range, 13–143). The cumulative incidence of grade II acute GVHD (aGVHD) at day +100 was 32.00 ± 0.91%. No one had grade III–IV aGVHD at day +100. The cumulative incidence of total chronic GVHD was 28.00 ± 0.85%. The overall survival was 71.78 ± 9.05% at a median follow-up of 42.08 months (range, 2.67–104). Promisingly, the protocol yielded a similar curative effect in both young and adult SAA patients.ConclusionsThe authors’ data suggest that co-transplantation of HLA-haploidentical HSCs and UC-MSCs may provide an effective and safe treatment for adult SAA. |
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