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Planned Granulocyte Colony-Stimulating Factor Adversely Impacts Survival after Allogeneic Hematopoietic Cell Transplantation Performed with Thymoglobulin for Myeloid Malignancy. Transplant Cell Ther 2021 Dec;27(12):993.e1-993.e8

Date

09/11/2021

Pubmed ID

34507002

Pubmed Central ID

PMC8671234

DOI

10.1016/j.jtct.2021.08.031

Scopus ID

2-s2.0-85120751167

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 <.0001; 21% versus 12%) compared to HCT without G-CSF. The 6-month incidence of viral infection was higher with G-CSF (56% versus 47%; P = .007), with a particular increase in Epstein-Barr virus infections (19% versus 11%; P = .002). The observed higher NRM with planned G-CSF led to lower overall survival (HR, 1.52; P = .0005; 61% versus 72%). There was no difference in GVHD risk between the treatment groups. We performed 2 subgroup analyses showing that our findings held true in patients age ≥50 years and in centers where G-CSF was used in some, but not all, patients. In allogeneic peripheral blood HCT performed with Thymoglobulin for AML and MDS, G-CSF administered early post-transplantation resulted in a 2-fold increase in NRM and a 10% absolute decrement in survival. The use of planned G-CSF in the early post-transplantation period should be carefully considered on an individual patient basis, weighing any perceived benefits against these risks.

Author List

Orfali N, Zhang MJ, Allbee-Johnson M, Boelens JJ, Artz AS, Brunstein CG, McNiece IK, Milano F, Abid MB, Chee L, Diaz MA, Grunwald MR, Hematti P, Hsu J, Lazarus HM, Munshi PN, Prestidge T, Ringden O, Rizzieri D, Riches ML, Seo S, Solh M, Solomon S, Szwajcer D, Yared J, van Besien K, Eapen M

Authors

Muhammad Bilal Abid MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Mary Eapen MBBS, DCh, MRCPI, MS Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin