Addition of ATG to the Conditioning Regimen in Unrelated Donor Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) from an unrelated donor (URD) is a suitable option for patients in need of a transplant when asibling donor is not available. Thanks to the recent advances in differentaspects of transplantation medicine, such as improvements in the criteriaof donor selection, well-tolerable conditioning regimen and progress inmanaging post-transplantation complications, Outcomes of URD-HSCThave improved considerably. Conditioning regimens are administered aspart of the pre-transplant treatment to achieve 2 goals: provide ampleimmunoablation to prevent graft rejection and eradicate the resistanttumor cells as much as possible. The conditioning regimens includechemotherapeutic agents most commonly, cyclophosphamide, basedon its antineoplastic and immunomodulatory properties. Because of thehigh probability of developing acute graft versus host disease (GvHD)with URD-SCT, anti-thymocyte globulin (ATG), is often administered asa part of the conditioning regimens for these transplants to reduce thisrisk of GvHD. ATG is a polyclonal immunoglobulin raised in rabbits orhorses against the Jurkat T cell line. These antibodies are directed againstlymphocyte surface molecules such as CD2, CD4, CD8, CD5, CD3,CD18, CD11a, CD45, and HLA-DR and are effective in destroying humanleukocytes. For the First time, it was reported that rabbit ATG resulted in asignificant reduction of acute and chronic GvHD but with an increase inserious infection. Afterward, many studies have investigated the preciseeffect of ATG on the incidence of GvHD, relapse and infection. It hasbeen shown that the Addition of ATG to the conditioning regimen, couldreduce long-term immunosuppressive use. Also, the decline of chronicGvHD has been reported in many studies. While reducing the risk ofdeveloping GvHD, administration of ATG preserves the anti-leukemiaeffect of the URD HCT However, a very recent study demonstrated theincreased use of blood products in patients received ATG-conditioningregimen, compared to alemtuzumab- conditioning regimen. Anotherdisadvantage of ATG administration mentioned in a study, is Epstein-Barr virus reactivation. But this problem can be solved by pre-emptiveor prophylactic treatment with rituximab. Overall, considering the resultof all studies in this field, ATG administration in conditioning regimen,associated with favorable outcome.

Keywords:

ATG , Graft-versus-host disease , Prophylaxis , Conditioning