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Frontiers of Medicine

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Front. Med.    2021, Vol. 15 Issue (5) : 718-727    https://doi.org/10.1007/s11684-020-0807-4
RESEARCH ARTICLE
Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia
Hongchen Liu1, Xiaoli Zheng2, Chengtao Zhang1, Jiajun Xie1, Beibei Gao1, Jing Shao1,3, Yan Yang1(), Hengxiang Wang2(), Jinsong Yan1()
1. Department of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Dalian Key Laboratory of Hematology, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Diamond Bay Institute of Hematology, the Second Hospital of Dalian Medical University, Dalian 116027, China
2. Department of Hematology, Air Force Medical Center, PLA, Beijing 100142, China
3. Department of Environmental Health and Toxicology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, School of Public Health, Dalian Medical University, Dalian 116044, China
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Abstract

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II–IV aGvHD, including two with grade III–IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.
Keywords severe aplastic anemia      non-severe acquired aplastic anemia      haploidentical bone marrow transplantation      outcomes     
Corresponding Author(s): Yan Yang,Hengxiang Wang,Jinsong Yan   
Online First Date: 13 July 2021    Issue Date: 01 November 2021
 Cite this article:   
Hongchen Liu,Xiaoli Zheng,Chengtao Zhang, et al. Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia[J]. Front. Med., 2021, 15(5): 718-727.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0807-4
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I5/718
No. Sex Age (year) Disease duration (year) ECOG Donor (donor/age (year)) Blood typing (donor/recipient) HLA matching aGvHD/cGvHD Serum ferritin (ng/mL) Survival
(month)		 Outcome
Prior to BMT Post BMT
1 M 15 8 3 Father/40 O/O 5/10 IV (GIT)/− 1001 1389 51 Alive
2 M 12 5.3 3 Father/38 B/A 5/10 I (GIT)/mild 7350 11 467 44 Alive
3 F 17 10 3 Father/53 B/O 5/10 II (GIT)/− 639 1832 42 Alive
4* M 17 4 2 Father/42 AB/AB 5/10 −/mild 893 1210 42 Alive
5 M 7 4.3 2 Father/28 O/O 5/10 −/− 512 958 40 Alive
6 M 35 22 2 Father/60 A/O 5/10 −/mild 3931 5190 37 Alive
7** M 26 21 3 Mother/49 B/O 5/10 3848 0 Death
8 M 21 16 3 Mother/47 O/O 5/10 I (skin)/moderate 5437 4586 34 Alive
9 M 13 11 3 Father/42 A/A 5/10 −/− 2227 2537 15 Death
10 F 22 4.5 3 Father/45 B/B 5/10 −/− 6666 1591 28 Alive
11 F 11 8 2 Father/38 O/O 5/10 −/− 1793 1800 55 Alive
12 F 5 2 2 Father/30 A/A 5/10 −/− 3578 4300 54 Alive
13 F 9 4 2 Father/34 AB/A 5/10 −/moderate 9559 8921 55 Alive
14 M 26 11.3 3 Mother/48 AB/A 5/10 I (skin)/− 7458 9233 53 Alive
15 M 16 1 2 Father/47 O/O 5/10 −/− 2669 2100 51 Alive
16 M 25 1.4 2 Sister/34 O/O 5/10 −/mild 2763 3202 51 Alive
17 M 15 1.2 2 Father/42 O/B 5/10 −/− 941 801 51 Alive
18 F 14 7 3 Father/43 A/A 5/10 II (Skin)/− 1738 1356 50 Alive
19 F 26 8 2 Father/49 O/B 5/10 −/− 5824 6320 43 Alive
20 F 27 13 3 Brother/22 A/O 5/10 −/− 2148 2254 39 Alive
21 M 19 10 3 Mother/43 O/O 5/10 III (GIT)/− 2821 3838 30 Alive
22 F 28 15 2 Brother/32 O/O 5/10 −/− 2632 22 714 10 Death
Tab.1  Demographic data and clinical features as well as outcomes of 22 patients with SAA-II
Before transplantation 30 days 60 days 90 days
Cells (×106/L), median (range)
Total lymphocytes 1092 (432–2604) 190 (31–523) 1036 (276–2806) 1183 (172–1984)
CD3+ 905 (410–2211) 85 (4–130) 864 (88–1729) 846 (49–1885)
CD4+ 343 (164–1318) 7 (0–47) 104 (10–200) 53 (16–309)
CD8+ 392 (183–956) 44 (2–73) 718 (72–1257) 502 (24–1504)
Natural killer 99 (3–434) 94 (22–345) 247 (29–612) 182 (61–540)
CD19+ 117 (19–241) 17 (2–58) 12 (0–374) 14 (1–260)
Immunoglobulin (g/L), median (range)
IgA 1.97 (1.26–2.90) 0.77 (0.47–0.89) 0.39 (0.25–0.92) 0.3 (0.23–1.15)
IgG 10.7 (7.74–17.7) 14.6 (13.3–16.4) 13.1 (7.34–20.4) 17.9 (0.97–20.1)
IgM 1.02 (0.61–2.17) 0.46 (0.31–0.83) 0.31 (0.19–0.31) 0.59 (0.16–23.8)
180 days 365 days 730 days
Cells (×106/L), median (range)
Total lymphocytes 1153 (837–1832) 983(772–2666) 1465(1405–2259)
CD3+ 714 (402–1239) 800 (679–1868) 1029 (948–1665)
CD4+ 139 (37–222) 216 (134–551) 303 (285–533)
CD8+ 450 (265–1053) 516 (459–1026) 658 (522–979)
Natural killer 267 (29–711) 198 (35–269) 113 (70–345)
CD19+ 153 (13–738) 108 (50–641) 346 (131–456)
Immunoglobulin (g/L), median (range)
IgA 0.4 (0.26–0.89) 0.82 (0.25–2.88) 1.20 (1.08–1.7)
IgG 7.77 (2.8–19.8) 10.3 (3.08–19.3) 11.2 (7.83–12.6)
IgM 0.48 (0.18–0.7) 0.71 (0.42–1.41) 0.69 (0.5–1.39)
Tab.2  Data of immune reconstitution
Patient No. Cellularity (%) CD34+ CD42b CD61
Before After Before After Before After Before After
1 <10 60 – + – + – +
4 <10 20–30 – + – + – +
12 <10 40–50 – + – + – +
13 <10 30–40 – + – + – +
14 <10 40 – + – + – +
15 <10 30–40 – + – + – +
17 <10 40 – + – + – +
Tab.3  Bone marrow biopsy in eight patients before and after bone marrow transplantation
Fig.1  Survival function of 22 patients with SAA-II after haploidentical bone marrow transplantation. (A) Overall survival (OS). The estimated OS at 36 months was 86.4%±0.73%. (B) Disease-free survival (DFS). The estimated DFS at 36 months was 86.4%±0.73%.
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