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1484 Anti-Thymocyte Globulin (ATG) for Prophylaxis of Severe Graft Vs. Host Disease after Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-AnalysisClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster I
Hematology Disease Topics & Pathways:
Biological, antibodies, Therapies, Adverse Events, Clinically relevant, transplantation, stem cells
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Muhammad Ashar Ali, MD1*, Muhammad Yasir Anwar1*, Sobia Aamir, MD, FCPS2*, Saad Ur Rahman, MBBS1*, Richi Kashyap, MD3*, Sana Irfan Khan, MD4*, Usman Ali Akbar, MBBS5*, Anum Waqar, MBBS6*, Anam Khan7*, Wajeeha Aiman, MD5* and Faiz Anwer, MD8

1King Edward Medical University, Lahore, Pakistan
2Children hospital and Institute of Child Health, Lahore, Pakistan
3Maulana Azad Medical College, New Delhi, India
4All India Institute Of Medical Sciences, Delhi, India
5Nishtar Medical University, Multan, Pakistan
6Fatima Jinnah Medical University, Lahore, Pakistan
7Jawaharlal Nehru Medical College, Delhi, India
8Taussig Cancer Institute, Cleveland Clinic, Cleveland


Hematopoietic stem cell transplantation (HSCT) is used for the treatment of multiple hematologic diseases. The donor cells kill the host malignant cells, but unfortunately, the immune response can cause graft vs. host disease (GvHD). Anti-thymocyte globulin (ATG) is an antibody derived from rabbits or horses. It targets antigens expressed on T-cells, B-cells, macrophages, natural killer cells, and dendritic cells, and used for the prevention of GvHD. We conducted a meta-analysis to assess the efficacy of ATG in preventing high-grade GvHD after hematopoietic stem cell transplant.


A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following mesh terms and Emtree terms, “antilymphocyte globulin” OR “antithymocyte globulin” AND “graft vs. host disease” from the inception of literature till 06/01/2020. We screened 5767 articles and included 10 randomized clinical trials (N=1,227) and 31 observational studies (N=14,895) in this meta-analysis. We extracted data for severe acute GvHD (grade III-IV or grade II-IV) and severe chronic GvHD (an extensive disease by Seattle criteria or moderate to severe disease according to NIH criteria). We excluded case reports, case series, preclinical trials, single-arm studies, review articles, meta-analysis, and controlled studies not providing any information about high-grade GvHD. We used the R programming language (version 4.0.2) to conduct a meta-analysis.


In 41 included studies (N=16,122), the median age was ≥40 years in 22 studies (N=12,099), ≤40 years in 16 studies (N=3536), and ≤18 years in 3 studies (N=487). 2986 patients had at least one HLA allele mismatch. Out of 41 studies, data for high-grade acute GvHD was available in 40 studies (N=16,047), and data for high-grade chronic GvHD was available in 33 studies (N=14,206), see Figure 1, 2.

For high-grade acute GvHD, risk ratio (RR) was 0.68 (I2=24%, 95% CI=0.61-0.75) in favor of the use of ATG vs. no use of ATG in the prophylaxis of GvHD with HSCT. In 9 RCTs (N=1,152), RR was 0.59 (I2=38%, CI=0.42-0.82) in favor of ATG use. High-grade acute GvHD significantly improved in all subgroups, i-e., peripheral blood (PB) /bone marrow (BM) HSCT from related donors (RR=0.73; 95% CI=0.61-0.88), PB/BM transplant from unrelated donors (RR=0.62; CI=0.52-0.72) and umbilical cord blood (UC) HSCT (RR=0.61; CI=0.43-0.88).

For high-grade chronic GvHD, RR was 0.47 (I2=49%, 95% CI=0.40-0.55) in favor of the use of ATG vs. no use of ATG in the prophylaxis of GvHD with HSCT. In 6 RCTs (N=714), RR was 0.40 (I2=58%, 95% CI=0.27-0.61) in favor of ATG use. High-grade chronic GvHD significantly improved with the use of ATG in both related donors (RR=0.44; 95% CI=0.34-0.58) and unrelated donors (RR=0.46; 95% CI=0.38-0.55) subgroups for BM / PB HSCT. However, there was no significant improvement in the risk of high-grade chronic GvHD with the use of ATG with cord blood HSCT (RR=0.98; 95% CI=0.73-1.31).


ATG is effective in the prophylaxis of severe acute GvHD irrespective of donor relationship or type of HSCT. ATG is also effective in the prophylaxis of severe chronic GvHD with bone marrow or peripheral blood HSCT except for cord blood HSCT. Additional multicenter randomized double-blinded clinical trials are needed to confirm these results.

Disclosures: Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

*signifies non-member of ASH