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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.

SUBMITTER: Ali R

PROVIDER: S-EPMC5744091 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Ali Robert R Ramdial Jeremy J Algaze Sandra S Beitinjaneh Amer A

Biomedicines 20171129 4

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 su ...[more]

PMID: 29186076

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Project description:Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received post-transplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3-4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09-2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04-2.02); P=0.03] and leukemia-free survival [HR 1.48 (95%CI: 1.03-2.12); P=0.03] than those in the anti-thymocyte globulin-based group. In the multivariate analysis, there was also a trend for a higher overall survival [HR 1.43 (95%CI: 0.98-2.09); P=0.06] for post-transplant cyclophosphamide-based regimen versus the anti-thymocyte globulin-based group. Notably, center experience was also associated with non-relapse mortality and graft-versus-host disease-free, relapse-free survival. Haplo-SCT using a post-transplant cyclophosphamide-based regimen can achieve better leukemia-free survival and graft-versus-host disease-free, relapse-free survival, lower incidence of graft-versus-host disease and non-relapse mortality as compared to anti-thymocyte globulin-based graft-versus-host disease prophylaxis in patients with acute myeloid leukemia.

Dataset Information

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

Publications

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

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