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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (2) : 153-163    https://doi.org/10.1007/s11684-017-0548-1
RESEARCH ARTICLE |
Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts
Xuying Pei1, Xiangyu Zhao1, Yu Wang1, Lanping Xu1, Xiaohui Zhang1, Kaiyan Liu1, Yingjun Chang1(), Xiaojun Huang1,2()
1. Peking University People’s Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China
2. Peking-Tsinghua Center for Life Sciences, Beijing 100044, China
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Abstract

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo-SCT) and without showing any of the following events: poor graft function, grades II?IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3+ T cells, CD8+ T cells, and CD19+ B cells, and very slow in CD4+ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation. We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.

Keywords immune reconstitution      hematopoietic stem cell transplantation      event-free patients      reference range     
Corresponding Authors: Yingjun Chang,Xiaojun Huang   
Just Accepted Date: 18 July 2017   Online First Date: 08 September 2017    Issue Date: 02 April 2018
 Cite this article:   
Xuying Pei,Xiangyu Zhao,Yu Wang, et al. Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts[J]. Front. Med., 2018, 12(2): 153-163.
 URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0548-1
http://academic.hep.com.cn/fmd/EN/Y2018/V12/I2/153
Fig.1  Flowchart of patient selection.
Variable Total (n = 144) HLA-identical (n = 59) Haploidentical (n = 85) P value
Age, year, median (range) 30 (3–59) 40 (22–59) 25 (3–55) <0.001
Child, n (%) 17 (11.81) 0 (0) 17 (20.00)
Adult, n (%) 127 (88.19) 59 (100) 68 (80.00)
Gender, n (%) 0.697
Male 93 (64.58) 37 (62.71) 56 (65.88)
Female 51 (35.42) 22 (37.29) 29 (34.12)
Disease type, n (%) 0.381
AML 72 (50.00) 34 (57.63) 38 (44.71)
ALL 44 (30.56) 12 (20.34) 32 (37.65)
MDS 12 (8.33) 5 (8.47) 7 (8.24)
CML 16 (11.11) 8 (13.56) 8 (9.41)
Disease status, n (%) 0.850
Standard risk 123 (85.42) 50 (84.75) 73 (85.88)
High risk 21 (14.58) 9 (15.25) 12 (14.12)
Donor-patient sex matched, n (%) 0.045
Male to male 59 (40.97) 19 (32.20) 40 (47.06)
Male to female 20 (13.89) 7 (11.86) 13 (15.29)
Female to male 39 (27.08) 20 (33.90) 19 (22.35)
Female to female 26 (18.06) 13 (22.03) 13 (15.29)
Donor-patient relationship, n (%) <0.001
Father/mother to child 49 (34.03) 0 (0) 49 (57.65)
Child to father/mother 4 (2.78) 0 (0) 4 (4.71)
Sibling 91 (63.19) 59 (100) 32 (37.65)
Follow-up time
Median, day (range) 1251 (392–1813) 1337 (392–1813) 1207 (468–1813) 0.864
Tab.1  Patient, disease, and donor characteristics
Fig.2  Long-term outcome in 144 recipients. (A) Probability of overall survival. (B) Cumulative incidence of relapse rate characterized by haplo-SCT modality.
Fig.3  Kinetics of immune reconstitution in event-free patients after transplantation. Data are presented as median cell counts with error bars indicating 25th–75th percentiles. The horizontal dotted lines represent the normal values from healthy cohorts, and the gray areas are the 25th–75th percentiles for the healthy cohorts. *P<0.05, **P<0.01 vs. healthy donors.
Factors Immune subset Day 30 Day 60 Day 90 Day 180 Day 365
HSCT type Lymphocyte
CD19+ B cell
CD3+ T cell
CD4+ T cell
CD4+ CD25+ T cell
CD4+ CD28+ T cell
CD8+ T cell
CD4:CD8 ratio
Age Lymphocyte
Gender Lymphocyte
CD3+ T cell
CD4+ T cell
Tab.2  Factors associated with immune cell subset counts as revealed by multivariate analysis
30 d 60 d 90 d
HLA-identical
Monocyte 738.92 (546.47–919.52) 482.01 (374.85–648.95) 430.56 (355.22–604.90)
Lymphocyte 557.60 (398.91–835.89) 1417.08 (1007.15–1960.91) 1630.20 (1179.44–2180.42)
CD19 + B cell 7.97 (3.59–16.74) 17.00 (7.30–34.09) 31.77 (13.97–76.82)
CD3+ T cell 370.16 (221.61–559.59) 1157.91 (632.08–1657.56) 1274.07 (813.81–1784.32)
CD4+ T cell 171.89 (92.28–268.98) 217.62 (147.89–362.86) 281.68 (159.66–449.88)
CD8+ T cell 157.57 (96.28–247.36) 707.35 (422.39–1242.52) 821.52 (517.07–1024.24)
CD4+CD25+ T cell 99.45 (58.03–158.71) 80.34 (58.32–116.38) 107.80 (52.33–161.72)
CD4+CD28+ T cell 80.72 (47.00–143.79) 46.56 (27.24–84.21) 57.87 (27.88–110.30)
CD8+CD28+ T cell 29.67 (17.27–49.75) 103.30 (52.53–149.07) 102.01 (58.82–171.11)
CD4CD8 T cell 38.69 (17.38–74.30) 86.75 (33.99–156.82) 97.49 (48.35–163.95)
Haploidentical
Monocyte 567.84 (339.63–914.39) 400.50 (228.74–561.27) 450.45 (311.70–580.11)
Lymphocyte 289.20 (129.58–414.16) 848.70 (486.09–1451.15) 1238.36 (852.24–1964.93)
CD19+ B cell 5.28 (2.54–11.82) 11.00 (4.06–27.05) 11.26 (4.58–26.52)
CD3+ T cell 110.64 (57.62–250.11) 608.26 (350.89–1089.21) 834.83 (524.55–1341.85)
CD4+ T cell 24.31 (9.27–69.34) 93.12 (54.81–148.07) 109.71 (63.11–190.08)
CD8+ T cell 71.92 (35.10–148.97) 493.93 (240.75–859.97) 684.00 (392.11–1098.09)
CD4+CD25+ T cell 11.18 (2.84–21.80) 19.07 (7.11–37.20) 23.29 (13.32–42.70)
CD4+CD28+ T cell 5.34 (1.33–14.87) 12.03 (6.23–27.72) 11.62 (6.14–24.37)
CD8+CD28+ T cell 23.95 (10.99–65.94) 126.50 (56.31–228.04) 157.88 (88.65–223.41)
CD4CD8 T cell 7.66 (2.50–15.26) 24.41 (11.06–57.93) 30.41 (15.77–59.32)
180 d 365 d
HLA-identical
Monocyte 479.94 (354.73–650.87) 522.56 (429.63–791.28)
Lymphocyte 1874.82 (1284.57–2379.67) 2638.48 (1848.90–3445.92)
CD19 + B cell 118.27 (62.33–222.55) 325.08 (144.85–533.83)
CD3+ T cell 1311.07 (916.73–1747.84) 1728.66 (1132.61–2463.98)
CD4+ T cell 291.50 (224.67–423.97) 440.55 (313.24–631.06)
CD8+ T cell 792.05 (504.56–1224.03) 1057.82 (614.85–1480.68)
CD4+CD25+ T cell 125.47 (80.69–168.47) 122.81 (78.65–185.62)
CD4+CD28+ T cell 69.12 (40.45–107.81) 91.18 (62.11–155.89)
CD8+CD28+ T cell 102.10 (66.83–144.37) 449.45 (238.71–749.03)
CD4CD8 T cell 91.46 (60.40–133.07) 110.50 (71.13–165.22)
Haploidentical
Monocyte 460.35 (310.28–579.55) 499.38 (390.74–615.03)
Lymphocyte 1669.80 (1149.33–2449.45) 2232.38 (1550.55–2856.45)
CD19+ B cell 69.84 (26.26–162.78) 242.95 (118.14–371.36)
CD3+ T cell 1194.15 (781.83–1879.41) 1561.06 (1162.98–2408.78)
CD4+ T cell 173.43 (112.29–285.73) 305.86 (230.81–438.35)
CD8+ T cell 945.63 (596.17–1426.72) 1035.30 (809.95–1761.59)
CD4+CD25+ T cell 48.58 (33.89–86.98) 91.28 (57.33–119.26)
CD4+CD28+ T cell 22.38 (11.98–41.31) 47.45 (27.50–80.94)
CD8+CD28+ T cell 138.33 (92.38–248.66) 175.65 (107.79–265.33)
CD4CD8 T cell 41.19 (24.43–91.84) 189.99 (123.72–368.34)
Tab.3  Reference value for immune cell subset counts after transplantation (median (25th–75th))
Fig.4  Immune reconstitution in HLA-identical siblings and haploidentical transplantation. Data are presented as median cell counts with error bars indicating the 25th–75th percentiles. The horizontal dotted lines represent the normal values from healthy cohorts, and gray areas represent the 25th–75th percentiles for the healthy cohorts. *P<0.05, **P<0.01 between the HLA-identical siblings and haploidentical transplantation modality.
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