The Role of Anti-Thymocyte Globulin or Alemtuzumab-Based Serotherapy in the Prophylaxis and Management of Graft-Versus-Host Disease

Abstract

Allogeneic hematopoietic stem cell transplant is an established treatment modality for hematologic and non-hematologic diseases. However, it is associated with acute and long-term sequelae which can translate into mortality. Graft-versus-host disease (GVHD) remains a glaring obstacle, especially with the advent of reduced-intensity conditioning. Serotherapy capitalizes on antibodies which target T cells and other immune cells to mitigate this effect. This article focuses on the utility of two such agents: anti-thymocyte globulin (ATG) and alemtuzumab. ATG has demonstrated benefit in prophylaxis against GVHD, especially in the chronic presentation. However, there is limited impact of ATG on overall survival and it has little utility in the treatment context. There may be an initial improvement, particularly in skin manifestations, but no substantial benefit has been elicited. Alemtuzumab has shown benefit in both prophylaxis and treatment of GVHD, but at the consequence of a more profound immunosuppressive phase, mandating aggressive viral prophylaxis. There remains heterogeneity in the doses and regimens of the agents, with no standardized protocol in place. Furthermore, it seems that once steroid-refractory GVHD has been established, there is little that can be offered to offset the ultimately dismal outcome. Here we present a systematic overview of ATG- or alemtuzumab-based serotherapy in the prophylaxis and management of GVHD.

Clinical Outcomes Using Mycophenolate and Tacrolimus for Graft-versus-Host Disease Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplant: A Single Institution Experience

“…No data could be extracted for the incidence of relapse, non-relapse mortality, grade III-IV acute GVHD, or GVHD relapse-free survival. The role of anti-thymocyte globulin (ATG) for acute GVHD prophylaxis has been well established in the literature, and ATG has been used at our institution; none of the patients in our study population from 2007-2017 received ATG [13]. As there is no comparator arm, outcomes were compared with the limited historical data available in the literature.…”

How to Make an Immune System and a Foreign Host Quickly Cohabit in Peace? The Challenge of Acute Graft-Versus-Host Disease Prevention After Allogeneic Hematopoietic Cell Transplantation

“…Both of these antibody preparations have a long half-life in the human plasma and therefore, once administered as part of the conditioning regimen, they exert their biological effects for several weeks after the graft infusion and induce profound depletion of both host and donor immune cells (128,129). Moreover, besides the pan T-cell depletion (Figure 1), ATG and ALEM also mediated a variety of other immune effects [detailed in other informative reviews (130,131)]. Several large randomized phase 3 trials have demonstrated the benefit on both aand cGVHD incidence of adding ATG to standard prophylaxis in the setting of MAC-alloHCT with PBSC (122)(123)(124)(125)(126).…”

The case for plerixafor to replace filgrastim as the optimal agent to mobilize peripheral blood donors for allogeneic hematopoietic cell transplantation

“…These include ex vivo manipulation of the donor source including CD34 selection, TCRa/b and CD19 B cell depletion, and CD45RA T-cell depletion [27−29]. There are also in vivo depletion approaches including peritransplantation ATG [30], alemtuzumab [31], posttransplantation rituximab [32], and PTCy [33,34]. At this point, it is unclear which of these approaches offers the optimal approach.…”