Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2019 Aug 12;17(1):156.
doi: 10.1186/s12916-019-1393-7.

Two dose levels of rabbit antithymocyte globulin as graft-versus-host disease prophylaxis in haploidentical stem cell transplantation: a multicenter randomized study

Ren Lin  1 , Yu Wang  2 , Fen Huang  1 , Zhiping Fan  1 , Shen Zhang  2 , Ting Yang  3 , Yajing Xu  4 , Na Xu  1 , Li Xuan  1 , Jieyu Ye  1 , Jing Sun  1 , Xiaojun Huang  5   6   7 , Qifa Liu  8   9
Affiliations
Randomized Controlled Trial

Two dose levels of rabbit antithymocyte globulin as graft-versus-host disease prophylaxis in haploidentical stem cell transplantation: a multicenter randomized study

Ren Lin et al. BMC Med. .

Abstract

Background: The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T cell-replete, G-CSF-primed haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

Methods: Four hundred and eight patients were enrolled in this multicenter study to evaluate the effect of 7.5 mg/kg and 10.0 mg/kg rabbit ATG on viral infections and GVHD prophylaxis after haplo-HSCT. The primary endpoint was EBV DNAemia within 1 year posttransplantation.

Results: The 1-year incidence of EBV DNAemia was 20.7% (95% confidence interval, 15.4-26.5) and 40.0% (33.3-46.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (P < 0.001). The 100-day cumulative incidence of grade II to IV aGVHD was 27.1% (21.1-33.4) and 25.4% (19.6-31.5) in the 7.5 mg/kg and 10.0 mg/kg ATG groups, respectively (P = 0.548). The 2-year incidence of chronic GVHD was 34.6% (27.8-41.4) and 36.2% (29.1-43.2) in the 7.5 mg and 10.0 mg groups (P = 0.814). The 1-year incidence of CMV DNAemia was 73.4% (67.2-79.4) and 83.4% (77.5-87.9) in the 7.5 mg/kg and 10.0 mg/kg groups (P = 0.038). The 3-year overall survival posttransplantation was 69.5% (63.2-75.8) and 63.5% (56.2-70.8), and the disease-free survival was 62.2% (55.3-69.1) and 60.3% (53.0-67.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (OS: P = 0.308; DFS: P = 0.660). The counts of EBV- and CMV-specific cytotoxic T cells (CTLs) were higher in the 7.5 mg/kg group than in the 10.0 mg/kg group early posttransplantation.

Conclusions: Compared with 10.0 mg/kg, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in haplo-HSCT, probably by affecting EBV- and CMV-specific CTLs.

Trial registration: clinicaltrials.gov, NCT01883180 . Registered 14 June 2013.

Keywords: Antithymocyte globulin; CMV; EBV; Graft-versus-host disease; Haploidentical hematopoietic stem cell transplantation.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials (CONSORT) diagram
Fig. 2
Fig. 2
Outcomes of haplo-HSCT in the two groups. a EBV DNAemia. b CMV DNAemia. c EBV-associated diseases. d CMV-associated diseases. e Grades II to IV acute GVHD (aGVHD). f Overall chronic GVHD (cGVHD)
Fig. 3
Fig. 3
Survival and relapse in the two groups. a Nonrelapse mortality (NRM). b Leukemia relapse. c Overall survival (OS). d Disease-free survival (DFS)
See this image and copyright information in PMC

References

    1. Han LJ, Wang Y, Fan ZP, Huang F, Zhou J, Fu YW, Qu H, Xuan L, Xu N, Ye JY, et al. Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission. Br J Haematol. 2017;179(1):120–130. doi: 10.1111/bjh.14854. - DOI - PubMed
    1. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Wu MQ, Wu DP, Huang XJ. Haploidentical versus matched-sibling transplant in adults with Philadelphia-negative high-risk acute lymphoblastic leukemia: a biologically phase III randomized study. Clin Cancer Res. 2016;22(14):3467–3476. doi: 10.1158/1078-0432.CCR-15-2335. - DOI - PubMed
    1. Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, Blaise D, Bosi A, Huang H, Karakasis D, et al. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia. 2015;29(9):1891–1900. doi: 10.1038/leu.2015.98. - DOI - PubMed
    1. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373(9674):1550–1561. doi: 10.1016/S0140-6736(09)60237-3. - DOI - PMC - PubMed
    1. Chang YJ, Huang XJ. Haploidentical stem cell transplantation: anti-thymocyte globulin-based experience. Semin Hematol. 2016;53(2):82–89. doi: 10.1053/j.seminhematol.2016.01.004. - DOI - PubMed

Publication types

MeSH terms

Associated data