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

Nina Orfali, Mei Jie Zhang, Mariam Allbee-Johnson, Jaap Jan Boelens, Andrew S. Artz, Claudio G. Brunstein, Ian K. McNiece, Filippo Milano, Muhammad Bilal Abid, Lynette Chee, Miguel A. Diaz, Michael R. Grunwald, Peiman Hematti, Jingmei Hsu, Hillard M. Lazarus, Pashna N. Munshi, Timothy Prestidge, Olle Ringden, David Rizzieri, Marcie L. RichesSachiko Seo, Melhem Solh, Scott Solomon, David Szwajcer, Jean Yared, Koen van Besien, Mary Eapen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)993.e1-993.e8
JournalTransplantation and Cellular Therapy
Volume27
Issue number12
DOIs
StatePublished - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy

Keywords

  • Antithymocyte globulin
  • Filgrastim
  • Granulocyte colony-stimulating factor
  • Hematopoietic stem cell transplantation
  • Thymoglobulin

Fingerprint

Dive into the research topics of 'Planned Granulocyte Colony-Stimulating Factor Adversely Impacts Survival after Allogeneic Hematopoietic Cell Transplantation Performed with Thymoglobulin for Myeloid Malignancy'. Together they form a unique fingerprint.

Cite this