Planned Granulocyte Colony-Stimulating Factor Adversely Impacts Survival after Allogeneic Hematopoietic Cell Transplantation Performed with Thymoglobulin for Myeloid Malignancy.

Abstract

The in vivo depletion of recipient and donor T lymphocytes using antithymocyte globulin (ATG; Thymoglobulin) is widely adopted in allogeneic hematopoietic stem cell transplantation (HCT) to reduce the incidence of both graft failure and graft-versus-host disease (GVHD). However, excess toxicity to donor lymphocytes may hamper immune reconstitution, compromising antitumor effects and increasing infection. Granulocyte-colony stimulating factor (G-CSF) administered early after HCT may increase ATG-mediated lymphotoxicity. This study aimed to investigate the effect of an interaction between ATG and post-transplantation granulocyte colony-stimulating factor (G-CSF) on allogeneic HCT outcomes, using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. We studied patients age ≥18 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who received Thymoglobulin-containing preparative regimens for HLA-matched sibling/unrelated or mismatched unrelated donor HCT between 2010 and 2018. The effect of planned G-CSF that was started between pretransplantation day 3 and post-transplantation day 12 was studied in comparison with transplantations that did not include G-CSF. Cox regression models were built to identify risk factors associated with outcomes at 1 year after transplantation. A total of 874 patients met the study eligibility criteria, of whom 459 (53%) received planned G-CSF. HCT with planned G-CSF was associated with a significantly increased risk for nonrelapse mortality (NRM) (hazard ratio [HR] 2.03; P