Impact of pre-transplant use of antibiotics on the graft-versus-host disease in adult patients with hematological malignancies

Hematology. 2021 Dec;26(1):96-102. doi: 10.1080/16078454.2021.1872957.

Abstract

Objectives: Changes in fecal microbiota affect the incidence and extent of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Most patients with hematological malignancies receive antibiotics for the treatment of febrile neutropenia prior to allogeneic HSCT, and pre-transplant use of antibiotics may influence the fecal microbiota and GVHD.

Methods: We retrospectively analysed consecutive adult patients with hematological malignancies who received allogeneic HSCT at Chungnam National University Hospital between 2007 and 2018. Pre-transplant use of antibiotics was defined as the use of antibiotics before conditioning chemotherapy.

Results: This study included 131 patients with a median age of 46 (range, 18-71) years: 76 (58%) patients were AML, 28 (21.4%) with ALL, 23 (17.6%) with MDS, and 4 (3.1%) with CML. All patients received calcineurin inhibitors with short-course methotrexate for GVHD prophylaxis. A total of 31 (23.7%) patients received anti-thymocyte globulin. All patients received antibiotics prior to HSCT: 70 (53.4%) patients received glycopeptide, 114 (87.0%) received cefepime, 87 (66.4%) received piperacillin/tazobactam, and 51 (38.9%) received carbapenem. Patients who received glycopeptide had more frequently extensive chronic GVHD (cGVHD) than those who did not (51.1% vs. 28.1% at 5 years) and had more frequently cGVHD of the lung (34.8% vs. 15.8% at 5 years). Pre-transplant use of glycopeptide did not affect the overall survival (OS) or GVHD- and relapse-free survival (GRFS) (median OS; 49 months in glycopeptide group vs. not reached in non-glycopeptide group, p=0.475; median GRFS; 9 months in glycopeptide group vs. 16 months in non-glycopeptide group, p=0.092).

Conclusion: Pre-transplant use of glycopeptide tends to increase the incidence of extensive cGVHD.

Keywords: GVHD; Glycopeptide; hematologic malignancies; hematopoietic stem cell transplantation.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / therapeutic use
  • Cefepime / therapeutic use
  • Disease-Free Survival
  • Female
  • Glycopeptides / therapeutic use
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Piperacillin, Tazobactam Drug Combination / therapeutic use
  • Retrospective Studies
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Glycopeptides
  • Immunosuppressive Agents
  • Piperacillin, Tazobactam Drug Combination
  • Cefepime
  • Methotrexate