Open-labelled, Interventional, randomized, controlled trial of Abatacept vs. Low dose Rabbit ATG/ATLG used for prophylaxis of graft versus host disease (GVHD) with Post transplant cyclophosphamide and Tacrolimus based regimens for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) of Hematological malignancies (A2G) Trial

·        Graft-versus-host disease (GVHD) remains a challenge after allogeneic hematopoietic cell transplantation (HCT). GVHD occurs when immunocompetent donor T cells recognize the recipient host as foreign and mount an immune response to allogeneic antigen-bearing cells with subsequent destruction of host tissues.

·        Despite current prophylactic strategies, morbidity and mortality remain high, and treatment of established GVHD can be difficult, with only about 40% of patients having a durable response to corticosteroid therapy.

·        The most common GVHD prophylaxis has historically been based on a calcineurin inhibitor and a short course of methotrexate (MTX). MTX, an antimetabolite and folate antagonist, attenuates T-cell activation at low non-cytotoxic doses and has had a long history in the prevention of GVHD.

·        Abatacept and ATG has shown great promise in further reduction of acute and chronic GVHD. When ATG was added to the preparative regimen in an intention to treat analysis, the rate of II-IV aGVHD (40% with abatacept and 42% with ATG) was similar but grade III-IV aGVHD remained significantly higher (3% with abatacept and 22% with ATG)

·        Further, Abatacept did not increase relapse rates; 22% of abatacept-treated patients relapsed in the 8/8 cohort and 9% for the 7/8 cohort.

·        The addition of abatacept appeared safe with similar engraftment (100% 7/8) and leukocyte reconstitution compared to controls. No significant increase in CMV or EBV reactivation or end-organ disease was observed.

·        However, there is no study with direct comparison between ATG and Abatacept.