Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts

doi:10.1007/s11684-017-0548-1

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 Huang^1,²(

)

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 Author(s): 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:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0548-1
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I2/153

Fig.1 Flowchart of patient selection.

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.

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)
CD4⁻CD8⁻ 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)
CD4⁻CD8⁻ 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)
CD4⁻CD8⁻ 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)
CD4⁻CD8⁻ 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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