Controversies and expectations for the prevention of GVHD: A biological and clinical perspective

Abstract

Severe acute and chronic graft versus host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Historically, cord blood and matched sibling transplantation has been associated with the lowest rates of GVHD. Newer methods have modified the lymphocyte components to minimize alloimmunity, including: anti-thymocyte globulin, post-transplant cyclophosphamide, alpha/beta T cell depletion, and abatacept. These agents have shown promise in reducing severe GVHD, however, can be associated with increased risks of relapse, graft failure, infections, and delayed immune reconstitution. Nonetheless, these GVHD prophylaxis strategies have permitted expansion of donor sources, especially critical for those of non-Caucasian decent who previously lacked transplant options. This review will focus on the biologic mechanisms driving GVHD, the method by which each agent impacts these activated pathways, and the clinical consequences of these modern prophylaxis approaches. In addition, emerging novel targeted strategies will be described. These GVHD prophylaxis approaches have revolutionized our ability to increase access to transplant and have provided important insights into the biology of GVHD and immune reconstitution.

Comparing the Outcomes of Matched and Mismatched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation with Different Anti-thymocyte Globulin Formulations. A Retrospective, Double-Centre Experience on Behalf of the Polish Adult Leukaemia Group

“…Consequently, endeavours are directed towards identifying the optimal GvHD prophylaxis protocol aimed at GvHD incidence, while maintaining a favourable graft-versus-leukemia (GvL) response and minimising the incidence of potentially lethal viral reactivations. This is of major importance notably in patients undergoing allo-HCT from mismatched related and unrelated donors with PBSC, given their well-established status as predisposing factors for GvHD [4,6]. In this study, we performed a retrospective analysis of patients suffering from various hematological conditions who sustained matched and mismatched unrelated allo-HCT and compared the outcomes of 40 patients who received ATG-T with those of 47 patients who were administered ATG-G.…”

“…The immunological consequences of ATG are also influenced by various factors, including timing of administration considering the day of transplantation, the cumulative dosage, and the recipientʹs lymphocyte count at the time of allo-HCT. Higher doses of rATG, a lower host total lymphocyte count, and closer timing to transplantation can lead to prolonged exposure to ATG after donor T cell infusion [4]. This results in a delayed immune reconstitution [17,18], thereby increasing the potential for vulnerability to infections, relapse, and the development of lymphoproliferative disorders following allo-HCT [19].…”

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in the Prophylaxis of Graft-Versus-Host Disease: A Systematic Review

“…This regimen is usually used in Haplo-HCT in China. 4 A total dose of 150 mg/m 2 fludarabine and 390 mg/m 2 busulfan was administered. 5 Doses were not reported.…”

“…GvHD stands as a paramount allo-HCT complication [1,2], as it detrimentally impacts both the duration and quality of life for post-transplant patients [3]. Elevated T cell count, HLA mismatch, and the employment of peripheral blood stem cells (PBSC) as a major transplant material nowadays represent factors of vulnerability for both aGvHD and cGvHD [4][5][6][7]. In spite of the administration of calcineurin inhibitors (CNIs) in conjunction with methotrexate (MTX) as prophylaxis of GvHD, numerous patients, ranging from 30% to 50%, develop aGvHD [8], while cGvHD persists in 30% to 70% of cases [9].…”

“…The immunological consequences of ATG are also influenced by various factors, including the cumulative dosage, timing of administration in relation to allo-HCT, and the lymphocyte count of the recipient at the time of the transplantation. Higher doses of ATG, closer timing to transplantation, and lower host total lymphocyte count can result in prolonged exposure to ATG following the infusion of donor T cells [4]. This, in turn, delays immune reconstitution [19,20], thus increasing the potential for relapse, susceptibility to infections, and the development of post-transplant lymphoproliferative disorders [21].…”