How I prevent GVHD in high-risk patients: posttransplant cyclophosphamide and beyond

• Published in: Blood 2023-01, Vol.141 (1), p.49-59
• Main Authors: Rimando, Joseph, McCurdy, Shannon R., Luznik, Leo
• Format: Article
• Language: English
• Subjects: Cyclophosphamide - therapeutic use; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Hematologic Neoplasms - drug therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Retrospective Studies; Tissue Donors; Transplantation Conditioning - adverse effects; Unrelated Donors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2021015129

[Display omitted] Advances in conditioning, graft-versus-host disease (GVHD) prophylaxis and antimicrobial prophylaxis have improved the safety of allogeneic hematopoietic cell transplantation (HCT), leading to a substantial increase in the number of patients transplanted each year. This influx of patients along with progress in remission-inducing and posttransplant maintenance strategies for hematologic malignancies has led to new GVHD risk factors and high-risk groups: HLA-mismatched related (haplo) and unrelated (MMUD) donors; older recipient age; posttransplant maintenance; prior checkpoint inhibitor and autologous HCT exposure; and patients with benign hematologic disorders. Along with the changing transplant population, the field of HCT has dramatically shifted in the past decade because of the widespread adoption of posttransplantation cyclophosphamide (PTCy), which has increased the use of HLA-mismatched related donors to levels comparable to HLA-matched related donors. Its success has led investigators to explore PTCy’s utility for HLA-matched HCT, where we predict it will be embraced as well. Additionally, combinations of promising new agents for GVHD prophylaxis such as abatacept and JAK inhibitors with PTCy inspire hope for an even safer transplant platform. Using 3 illustrative cases, we review our current approach to transplantation of patients at high risk of GVHD using our modern armamentarium. Edited by Associate Editor Robert Zeiser, this How I Treat series focuses on post–allogeneic transplant management of high-risk patients. These patients are at risk for relapse of malignancy and severe graft-versus-host disease (GVHD). Two articles in the series discuss adoptive cellular immunotherapy and maintenance therapy to preempt relapse of acute myeloid leukemia. The third article addresses the state of the art for preventing GVHD in this subset of stem cell transplant recipients.