Efficacy of hematopoietic stem cell transplantation in the treatment of children with non-severe aplastic anemia
Man Zhang
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorGuanghua Zhu
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorLixiao Cai
Department of Stem Cell Transplantation, National Center for Children's Health, Baoding Children's Hospital, Baoding, China
Search for more papers by this authorMeng Yuan
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorRunhui Wu
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorChenguang Jia
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorBin Wang
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorJie Zheng
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorJie Ma
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorCorresponding Author
Maoquan Qin
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Correspondence
Sidan Li and Maoquan Qin, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Email: [email protected] (S.L.); Email: [email protected] (M.Q.)
Search for more papers by this authorCorresponding Author
Sidan Li
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital Chinese Academy of Medical Sciences, Langfang, China
Correspondence
Sidan Li and Maoquan Qin, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Email: [email protected] (S.L.); Email: [email protected] (M.Q.)
Search for more papers by this authorMan Zhang
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorGuanghua Zhu
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorLixiao Cai
Department of Stem Cell Transplantation, National Center for Children's Health, Baoding Children's Hospital, Baoding, China
Search for more papers by this authorMeng Yuan
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorRunhui Wu
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorChenguang Jia
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorBin Wang
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorJie Zheng
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorJie Ma
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Search for more papers by this authorCorresponding Author
Maoquan Qin
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Correspondence
Sidan Li and Maoquan Qin, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Email: [email protected] (S.L.); Email: [email protected] (M.Q.)
Search for more papers by this authorCorresponding Author
Sidan Li
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital Chinese Academy of Medical Sciences, Langfang, China
Correspondence
Sidan Li and Maoquan Qin, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Email: [email protected] (S.L.); Email: [email protected] (M.Q.)
Search for more papers by this authorMan Zhang, Guanghua Zhu and Lixiao Cai contributed equally to this work and should be considered co-first authors.
Funding information
This study was supported by Capital Medical University “Undergraduate Scientific Research Innovation” project, Grant/Award Number: XSKY2021340.
Abstract
Background
Non-severe aplastic anemia is more likely to develop into severe aplastic anemia, and there is no widely accepted treatment plan at present. Hematopoietic stem cell transplantation might be a new therapeutic strategy.
Methods
Retrospectively analyzed 32 patients with non-severe aplastic anemia who underwent hematopoietic stem cell transplantation from September 2007 to September 2020, and the 5-year estimated overall survival rate and the incidence of graft-versus-host disease were analyzed to evaluate the efficacy and safety of hematopoietic stem cell transplantation in the treatment of pediatric non-severe aplastic anemia.
Results
Thirty-two patients who underwent transplantation, 29 patients (90.6%) survived, 3 patients (9.4%) died. The incidence of acute graft-versus-host disease was 51.6% (16/31), including 15 cases (48.4%) of grade I-II and 1 case (3.2%) of grade III–IV. The incidence of chronic graft-versus-host disease was 38.7% (12/31). The 5-year overall survival rate was 91.8%.
Conclusions
Hematopoietic stem cell transplantation is a practicable, safe, and effective treatment option for non-severe aplastic anemia pediatric patients who are suitable for transplant.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1Yang S, Yuan X, Ma R, et al. Comparison of outcomes of frontline immunosuppressive therapy and frontline haploidentical hematopoietic stem cell transplantation for children with severe aplastic anemia who lack an HLA-matched sibling donor. Biol Blood Marrow Transplant. 2019; 25: 975-980.
- 2Killick SB, Bown N, Cavenagh J, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016; 172(2): 187-207.
- 3 Red Blood Cell Disease (Anemia) Group, Chinese Society of Hematology, Chinese Medical Association. Chinese expert consensus on the diagnosis and treatment of aplastic anemia (2017). Zhonghua Xue Ye Xue Za Zhi. 2017; 38(1): 1-5.
- 4Marsh JCW, Ball SE, Cavenagh J, et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009; 147: 43-70.
- 5Lan L, Zhi-liang X. Progress on diagnosis and management of acquired aplastic anemia in children. Occupation Health. 2016; 32(20): 2877-2880.
- 6Xiao-tian X. Understanding and practice of “suggestions on diagnosis and treatment of children's acquired aplastic anemia”. J Chin Pediatr Blood Cancer. 2015; 20(4): 215-217.
- 7Camitta BM, Storb R, Thomas ED. Aplastic anemia (second of two parts): pathogenesis, diagnosis, treatment, and prognosis. N Engl J Med. 1982; 306(12): 712-718.
- 8Martino R, Romero P, Subirá M, et al. Comparison of the classic Glucksberg criteria and the IBMTR severity index for grading acute graft-versus-host disease following HLA-identical sibling stem cell transplantation. Int Bone Marrow Transplant Registry. 1999; 24: 283-287.
- 9Li S, Wang B, Fu L, et al. Hematopoietic stem cell transplantation without in vivo T-cell depletion for pediatric aplastic anemia: a single-center experience. Pediatr Transplant. 2018; 22(5):e13204.
- 10Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. the 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015; 21(3): 389-401.
- 11 Hematopoietic Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association; China Association for the Prevention of Hematology Diseases. Chinese consensus on the diagnosis and management of chronic graft-versus-host disease (2021). Zhonghua Xue Ye Xue Za Zhi. 2021; 42(4): 265-275.
- 12Chang Y, Liu D, Xu L, et al. Factors influencing engraftment in hematological patients after human leukocyte antigen matched sibling allogeneic blood and marrow transplantation. Zhonghua Nei Ke Za Zhi. 2009; 48: 647-650.
- 13Ferrà C, Sanz J, Dı´az-Pe´rez M, et al. Outcome of graft failure after allogeneic stem cell transplant: study of 89 patients. Leuk Lymphoma. 2015; 56(3): 656-662.
- 14Dufour C, Pillon M, Sociè G, et al. Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant. Br J Haematol. 2015; 169: 565-573.
- 15Holtan SG, DeFor TE, Lazaryan A, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015; 125(8): 1333-1338.
- 16Im SH, Kim BR, Park SM, et al. Better failure-free survival and graft-versus-host disease-free/failure free survival with fludarabine-based conditioning in stem cell transplantation for aplastic anemia in children. J Korean Med Sci. 2020; 35(7):e46.
- 17Howard SC, Naidu PE, Hu XJ, et al. Natural history of moderate aplastic anemia in children. Pediatr Blood Cancer. 2004; 43(5): 545-551.
- 18Nishio N, Yagasaki H, Takahashi Y, et al. Natural history of transfusion-independent non-severe aplastic anemia in children. Int J Hematol. 2009; 89(4): 409-413.
- 19Chen FF, Guo ZW, Zhang LN, et al. The change of quality of life in 52 patients with non-severe aplastic anemia after cyclosporine a therapy. Zhonghua Xue Ye Xue Za Zhi. 2020; 41(10): 806-810.
- 20Dufour C, Pillon M, Passweg J, et al. Outcome of aplastic anemia in adolescence: a survey of the severe aplastic anemia working Party of the European Group for blood and marrow transplantation. Haematologica. 2014; 99(10): 1574-1581.
- 21Yan S, Runhui W, Jie Z, et al. Efficacy of cyclosporine a on treatment of 126 children with non-severe aplastic anemia. J Clin Pediatrics. 2015; 33(05): 413-416.
- 22Wang S, Chen Y, Zou Y, Zheng Y, Zhu X. The progression risk factors of children with transfusion-independent non-severe aplastic anemia. Int J Hematol. 2013; 97(2): 210-215.
- 23Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012; 367: 11-19.
- 24Scheinberg P, Wu CO, Nunez O, et al. Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study. Haematologica. 2009; 94: 348-354.
- 25Maciejewski JP, Selleri C, Sato T, Anderson S, Young NS. A severe and consistent deficit in marrow and circulating primitive hematopoietic cells (long-term culture-initiating cells) in acquired aplastic anemia. Blood. 1996; 88(6): 1983-1991.
- 26Scheinberg P, Wu CO, Nunez O, Young NS. Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol. 2009; 144(2): 206-216.
- 27Fan X, Desmond R, Winkler T, et al. Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias. Blood Adv. 2020; 4(8): 1700-1710.
- 28Mishra K, Pramanik S, Jandial A, et al. Real-world experience of eltrombopag in immune thrombocytopenia. Am J Blood Res. 2020; 10(5): 240-251.
- 29Desmond R, Townsley DM, Dumitriu B, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014; 123(12): 1818-1825.
- 30Maury S, Balère-Appert M, Chir Z, et al. Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica. 2007; 92: 589-596.
- 31Viollier R, Socié G, Tichelli A, et al. Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transplant. 2008; 41(1): 45-50.
- 32Kennedy-Nasser AA, Leung KS, Mahajan A, et al. Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia. Biol Blood Marrow Transplant. 2006; 12: 1277-1284.
- 33Locasciulli A, Oneto R, Bacigalupo A, et al. Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2007; 92(1): 11-18.
- 34Bacigalupo A, Socie' G, Lanino E, et al. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party. Haematologica. 2010; 95(6): 976-982.
- 35Hongfei W, Xinsheng X, Dingming W, et al. Efficacy of haploidentical allogeneic hematopoietic stem cell transplantation for sever aplastic anemia: a report of 40 cases. Chin J Organ Transplant. 2019; 3: 153-157.
- 36Ying W, Fu-xu W, Fu-tian M, et al. Comparision of the allogeneic hematopoietic stem cell transplantation between human leucocyte antigen-matched donor and haploidentical donor on patients with transfusion-dependent non-severe aplastic anemia. J Hebei Med Univ. 2021; 42(7): 779-783.
- 37Xu Z, Zhou M, Jia J, et al. Immunosuppressive therapy versus haploidentical transplantation in adults with acquired severe aplastic anemia. Bone Marrow Transplant. 2019; 54(8): 1319-1326.
- 38Liu L, Zhao X, Miao M, et al. Inefficacy of immunosuppressive therapy for severe aplastic anemia progressing from non-SAA: improved outcome after allogeneic hematopoietic stem cell transplantation. Front Oncol. 2021; 11: 739561.
Citing Literature
