Cyclophosphamide-free Mobilisation Increases Safety While Preserving the Efficacy of Autologous Haematopoietic Stem Cell Transplantation in Refractory Crohn's Disease Patients

J Crohns Colitis. 2024 Oct 15;18(10):1701-1712. doi: 10.1093/ecco-jcc/jjae076.

Abstract

Background and aim: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for refractory Crohn's disease [CD]. However, high adverse event rates related to chemotherapy toxicity and immunosuppression limit its applicability. This study aims to evaluate AHSCT's safety and efficacy using a cyclophosphamide [Cy]-free mobilisation regimen.

Methods: A prospective, observational study included 14 refractory CD patients undergoing AHSCT between June 2017 and October 2022. The protocol involved outpatient mobilisation with G-CSF 12-16 μg/kg/daily for 5 days, and optional Plerixafor 240 μg/d [1-2 doses] if the CD34 + cell count target was unmet. Standard conditioning with Cy and anti-thymocyte globulin was administered. Clinical, endoscopic, and radiological assessments were conducted at baseline and during follow-up.

Results: All patients achieved successful outpatient mobilisation [seven patients needed Plerixafor] and underwent transplantation. Median follow-up was 106 weeks (interquartile range [IQR] 52-348). No mobilisation-related serious adverse events [SAEs] or CD worsening occurred. Clinical and endoscopic remission rates were 71% and 41.7% at 26 weeks, 64% and 25% at 52 weeks, and 71% and 16.7% at the last follow-up, respectively. The percentage of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 14% at 26 weeks, 57% at 52 weeks, and 86% at the last follow-up, respectively. Peripheral blood cell populations and antibody levels post-AHSCT were comparable to Cy-based mobilisation.

Conclusions: Cy-free mobilisation is safe and feasible in refractory CD patients undergoing AHSCT. Although relapse occurs in a significant proportion of patients, clinical and endoscopic responses are achieved upon CD-specific therapy reintroduction.

Keywords: Crohn; Transplant; safety.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Benzylamines
  • Crohn Disease* / therapy
  • Cyclams
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Stem Cell Mobilization* / methods
  • Hematopoietic Stem Cell Transplantation* / methods
  • Heterocyclic Compounds / administration & dosage
  • Heterocyclic Compounds / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Prospective Studies
  • Transplantation Conditioning / methods
  • Transplantation, Autologous* / methods
  • Treatment Outcome
  • Young Adult

Substances

  • plerixafor
  • Benzylamines
  • Cyclams
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Immunosuppressive Agents
  • Heterocyclic Compounds