Research advances on haploidentical hematopoietic stem cell transplantation in the treatment of severe aplastic anemia in children

GAO Yang-Yang; CHEN Xiao-Juan; LUO Rong-Mu

doi:10.7499/j.issn.1008-8830.2105073

PDF(550 KB)

Chinese Journal of Contemporary Pediatrics ›› 2021, Vol. 23 ›› Issue (8) : 854-859. DOI: 10.7499/j.issn.1008-8830.2105073

REVIEW

Research advances on haploidentical hematopoietic stem cell transplantation in the treatment of severe aplastic anemia in children

GAO Yang-Yang, CHEN Xiao-Juan, LUO Rong-Mu

Author information +

History +

Abstract

Haploidentical hematopoietic stem cell transplantation is a recommended alternative therapy for children with severe aplastic anemia who lack a human leukocyte antigen (HLA)-identical sibling donor and do not respond well to immunosuppressive therapy; however, due to non-identical HLA, the patients may have donor-specific anti-HLA antibody, which may lead to a relatively high incidence rate of poor graft function. Compared with HLA-identical transplantation, conditioning regimen for haploidentical transplantation still needs to be explored. This article reviews the detection and treatment of donor-specific anti-HLA antibody, the selection of conditioning regimen, and the mechanism and treatment of poor graft function in haploidentical hematopoietic stem cell transplantation.

Key words

Severe aplastic anemia / Haploidentical hematopoietic stem cell transplantation / Donor-specific anti-HLA antibody / Conditioning regimen / Poor graft function / Child

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

GAO Yang-Yang, CHEN Xiao-Juan, LUO Rong-Mu. Research advances on haploidentical hematopoietic stem cell transplantation in the treatment of severe aplastic anemia in children[J]. Chinese Journal of Contemporary Pediatrics. 2021, 23(8): 854-859 https://doi.org/10.7499/j.issn.1008-8830.2105073

References

1 Young NS. Aplastic anemia[J]. N Engl J Med, 2018, 379(17): 1643-1656. DOI: 10.1056/NEJMra1413485. PMID: 30354958. PMCID: PMC6467577.
2 ElGohary G, El Fakih R, de Latour R, et al. Haploidentical hematopoietic stem cell transplantation in aplastic anemia: a systematic review and meta-analysis of clinical outcome on behalf of the severe aplastic anemia working party of the European group for blood and marrow transplantation (SAAWP of EBMT)[J]. Bone Marrow Transplant, 2020, 55(10): 1906-1917. DOI: 10.1038/s41409-020-0897-2. PMID: 32346079.
3 Kojima S. Why is the incidence of aplastic anemia higher in Asia?[J]. Expert Rev Hematol, 2017, 10(4): 277-279. DOI: 10.1080/17474086.2017.1302797. PMID: 28264622.
4 Xu LP, Zhang XH, Wang FR, et al. Haploidentical transplantation for pediatric patients with acquired severe aplastic anemia[J]. Bone Marrow Transplant, 2017, 52(3): 381-387. DOI: 10.1038/bmt.2016.281. PMID: 27941773.
5 Peslak SA, Olson T, Babushok DV. Diagnosis and treatment of aplastic anemia[J]. Curr Treat Options Oncol, 2017, 18(12): 70. DOI: 10.1007/s11864-017-0511-z. PMID: 29143887. PMCID: PMC5804354.
6 李泊涵, 陆芹, 卞馨妮, 等. 单倍体造血干细胞移植对儿童重型再生障碍性贫血治疗的并发症分析[J]. 中华细胞与干细胞杂志(电子版), 2020, 10(2): 67-75. DOI: 10.3877/cma.j.issn.2095-1221.2020.02.001.
7 Xu LP, Wang SQ, Wu DP, et al. Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study[J]. Br J Haematol, 2016, 175(2): 265-274. DOI: 10.1111/bjh.14225. PMID: 27352174.
8 国家卫生健康委办公厅. 儿童再生障碍性贫血诊疗规范(2019年版)[J]. 全科医学临床与教育, 2019, 17(11): 965-969. DOI: 10.13558/j.cnki.issn1672-3686.2019.011.002.
9 Xu LP, Jin S, Wang SQ, et al. Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant[J]. J Hematol Oncol, 2017, 10(1): 25. DOI: 10.1186/s13045-017-0398-y. PMID: 28107815. PMCID: PMC5251320.
10 Xu LP, Chen H, Chen J, et al. The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology[J]. J Hematol Oncol, 2018, 11(1): 33. DOI: 10.1186/s13045-018-0564-x. PMID: 29495966. PMCID: PMC5833104.
11 张素平, 万鼎铭, 刘玉峰, 等. 单倍体造血干细胞移植与强化免疫抑制治疗儿童重型再生障碍性贫血的临床观察[J]. 中华实用儿科临床杂志, 2020, 35(15): 1161-1165. DOI: 10.3760/cma.j.cn101070-20190517-00422.
12 Ciurea SO, Thall PF, Wang XE, et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation[J]. Blood, 2011, 118(22): 5957-5964. DOI: 10.1182/blood-2011-06-362111. PMID: 21967975. PMCID: PMC3761379.
13 Ciurea SO, Thall PF, Milton DR, et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2015, 21(8): 1392-1398. DOI: 10.1016/j.bbmt.2015.05.001. PMID: 25985919. PMCID: PMC4506716.
14 Ciurea SO, Cao K, Fernadez-Vina M, et al. The European Society for Blood and Marrow Transplantation (EBMT) consensus guidelines for the detection and treatment of donor-specific anti-HLA antibodies (DSA) in haploidentical hematopoietic cell transplantation[J]. Bone Marrow Transplant, 2018, 53(5): 521-534. DOI: 10.1038/s41409-017-0062-8. PMID: 29335625. PMCID: PMC7232774.
15 Wang Y, Chang YJ, Xu LP, et al. Who is the best donor for a related HLA haplotype-mismatched transplant?[J]. Blood, 2014, 124(6): 843-850. DOI: 10.1182/blood-2014-03-563130. PMID: 24916508.
16 Xu LP, Wang SQ, Ma YR, et al. Who is the best haploidentical donor for acquired severe aplastic anemia? Experience from a multicenter study[J]. J Hematol Oncol, 2019, 12(1): 87. DOI: 10.1186/s13045-019-0775-9. PMID: 31477147. PMCID: PMC6719398.
17 Wang Y, Zhao XY, Xu LP, et al. Lower incidence of acute GVHD is associated with the rapid recovery of CD4+CD25+CD45RA+ regulatory T cells in patients who received haploidentical allografts from NIMA-mismatched donors: a retrospective (development) and prospective (validation) cohort-based study[J]. Oncoimmunology, 2016, 5(12): e1242546. DOI: 10.1080/2162402X.2016.1242546. PMID: 28180031. PMCID: PMC5215191.
18 Sun YQ, Chang YJ, Huang XJ. Update on current research into haploidentical hematopoietic stem cell transplantation[J]. Expert Rev Hematol, 2018, 11(4): 273-284. DOI: 10.1080/17474086.2018.1447379. PMID: 29493370.
19 Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions[J]. Biol Blood Marrow Transplant, 2009, 15(12): 1628-1633. DOI: 10.1016/j.bbmt.2009.07.004. PMID: 19896087. PMCID: PMC2861656.
20 Wu YM, Luo RM, Cao YB, et al. Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning[J]. Oncotarget, 2017, 8(48): 83817-83830. DOI: 10.18632/oncotarget.19745. PMID: 29137385. PMCID: PMC5663557.
21 Gao L, Li Y, Zhang Y, et al. Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell depletion for adult severe aplastic anemia after modified conditioning and supportive therapy[J]. Bone Marrow Transplant, 2014, 49(4): 519-524. DOI: 10.1038/bmt.2013.224. PMID: 24464145.
22 Dulley FL, Vigorito AC, Aranha FJ, et al. Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection[J]. Bone Marrow Transplant, 2004, 33(1): 9-13. DOI: 10.1038/sj.bmt.1704325. PMID: 14578930.
23 Lee SE, Park SS, Jeon YW, et al. Optimal conditioning regimen for haplo-identical stem cell transplantation in adult patients with acquired severe aplastic anemia: prospective de-escalation study of TBI and ATG dose[J]. Am J Hematol, 2018, 93(11): 1368-1375. DOI: 10.1002/ajh.25257. PMID: 30117176.
24 Lee SE, Min GJ, Park SS, et al. Outcomes of haploidentical stem cell transplantation using total body irradiation (600 cGy) and fludarabine with antithymocyte globulin in adult patients with severe aplastic anemia: a prospective phase Ⅱ study[J]. Biol Blood Marrow Transplant, 2020, 26(10): 1906-1914. DOI: 10.1016/j.bbmt.2020.06.024. PMID: 32634577.
25 赵晨, 黄晓军, 孙于谦, 等. 单倍型造血干细胞移植后原发性植入功能不良对巨细胞病毒肺炎的影响[J]. 中华血液学杂志, 2020, 41(7): 552-556. DOI: 10.3760/cma.j.issn.0253-2727.2020.07.004. PMID: 32810961. PMCID: PMC7449765.
26 Sun YQ, He GL, Chang YJ, et al. The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation[J]. Ann Hematol, 2015, 94(10): 1699-1705. DOI: 10.1007/s00277-015-2440-x. PMID: 26152553.
27 费新红, 贺俊宝, 程昊钰, 等. 纯化供者CD34+细胞输注治疗单倍型造血干细胞移植后移植物功能不良12例临床分析[J]. 中华血液学杂志, 2018, 39(10): 828-832. DOI: 10.3760/cma.j.issn.0253-2727.2018.10.008. PMID: 30369204. PMCID: PMC7348294.
28 Stasia A, Ghiso A, Galaverna F, et al. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2014, 20(9): 1440-1443. DOI: 10.1016/j.bbmt.2014.05.016. PMID: 24862637.
29 Zhao YM, Gao F, Shi JM, et al. Incidence, risk factors, and outcomes of primary poor graft function after allogeneic hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2019, 25(9): 1898-1907. DOI: 10.1016/j.bbmt.2019.05.036. PMID: 31176790.
30 Chang YJ, Zhao XY, Xu LP, et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets[J]. J Hematol Oncol, 2015, 8: 84. DOI: 10.1186/s13045-015-0182-9. PMID: 26156584. PMCID: PMC4496923.
31 Sun YQ, Wang Y, Zhang XH, et al. Virus reactivation and low dose of CD34+ cell, rather than haploidentical transplantation, were associated with secondary poor graft function within the first 100 days after allogeneic stem cell transplantation[J]. Ann Hematol, 2019, 98(8): 1877-1883. DOI: 10.1007/s00277-019-03715-w. PMID: 31144019.
32 Cho SY, Lee DG, Kim HJ. Cytomegalovirus infections after hematopoietic stem cell transplantation: current status and future immunotherapy[J]. Int J Mol Sci, 2019, 20(11): 2666. DOI: 10.3390/ijms20112666. PMID: 31151230. PMCID: PMC6600658.
33 Peralvo J, Bacigalupo A, Pittaluga PA, et al. Poor graft function associated with graft-versus-host disease after allogeneic marrow transplantation[J]. Bone Marrow Transplant, 1987, 2(3): 279-285. PMID:3332176.
34 Isidori A, Borin L, Elli E, et al. Iron toxicity—its effect on the bone marrow[J]. Blood Rev, 2018, 32(6): 473-479. DOI: 10.1016/j.blre.2018.04.004. PMID: 29699840.
35 Kim H, Im HJ, Koh KN, et al. Comparable outcome with a faster engraftment of optimized haploidentical hematopoietic stem cell transplantation compared with transplantations from other donor types in pediatric acquired aplastic anemia[J]. Biol Blood Marrow Transplant, 2019, 25(5): 965-974. DOI: 10.1016/j.bbmt.2019.01.010. PMID: 30639824.
36 Liesveld JL. Trouble in the niche? Send in a statin[J]. Blood, 2016, 128(25): 2877-2878. DOI: 10.1182/blood-2016-11-748194. PMID: 28007732.
37 Shi MM, Kong Y, Song Y, et al. Atorvastatin enhances endothelial cell function in posttransplant poor graft function[J]. Blood, 2016, 128(25): 2988-2999. DOI: 10.1182/blood-2016-03-702803. PMID: 27769957.
38 Kong Y, Song Y, Hu Y, et al. Increased reactive oxygen species and exhaustion of quiescent CD34-positive bone marrow cells may contribute to poor graft function after allotransplants[J]. Oncotarget, 2016, 7(21): 30892-30906. DOI: 10.18632/oncotarget.8810. PMID: 27105530. PMCID: PMC5058726.
39 Zhao HY, Lyu ZS, Duan CW, et al. An unbalanced monocyte macrophage polarization in the bone marrow microenvironment of patients with poor graft function after allogeneic haematopoietic stem cell transplantation[J]. Br J Haematol, 2018, 182(5): 679-692. DOI: 10.1111/bjh.15452. PMID: 29974948.
40 Kong Y, Wang YT, Cao XN, et al. Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation[J]. J Transl Med, 2017, 15(1): 57. DOI: 10.1186/s12967-017-1159-y. PMID: 28292332. PMCID: PMC5351211.
41 Wang YT, Kong Y, Song Y, et al. Increased type 1 immune response in the bone marrow immune microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2016, 22(8): 1376-1382. DOI: 10.1016/j.bbmt.2016.04.016. PMID: 27131864.
42 Liu XD, Wu MQ, Peng YW, et al. Improvement in poor graft function after allogeneic hematopoietic stem cell transplantation upon administration of mesenchymal stem cells from third-party donors: a pilot prospective study[J]. Cell Transplant, 2014, 23(9): 1087-1098. DOI: 10.3727/096368912X661319. PMID: 23294601.
43 Ding L, Han DM, Zheng XL, et al. 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[J]. Stem Cells Transl Med, 2021, 10(2): 291-302. DOI: 10.1002/sctm.20-0345. PMID: 32978903. PMCID: PMC7848315.
44 Song Y, Zhao HY, Lyu ZS, et al. Dysfunctional bone marrow mesenchymal stem cells in patients with poor graft function after allogeneic hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2018, 24(10): 1981-1989. DOI: 10.1016/j.bbmt.2018.06.021. PMID: 29933074.