Outcome of treosulfan-based reduced-toxicity conditioning regimens for HSCT in high-risk patients with primary immune deficiencies

Pediatr Transplant. 2018 Nov;22(7):e13266. doi: 10.1111/petr.13266. Epub 2018 Jul 11.

Abstract

Introduction: HSCT is the curative therapeutic option in PIDs. Due to the increase in survival rates, reduced-toxicity conditioning regimens with treosulfan have become another alternative. The purpose of this retrospective study was to analyze the outcome of treosulfan-based conditioning before HSCT for patients with PID.

Method: A total of 15 patients that received a treosulfan-based conditioning regimen for HSCT were recruited. Type of diagnosis, donor and stem cell source, pretransplant organ damage, infections, engraftment, chimerism, and transplant-related toxicities were analyzed.

Results: At a median follow-up time of 32 months, the overall survival was 86.7%. Following HSCT, 14 of 15 patients had engraftment, with 86.7% of the cohort having full-donor chimerism. The most common toxicity was seen on the skin (53.3%). Acute GVHD and chronic GVHD were documented in 53% and 20% of the study population, respectively. Although the cohort consisted of patients with pretransplant liver damage, SOS manifestations were documented in 20%.

Conclusion: Treosulfan-based conditioning regimens before HSCT are associated with lower toxicity compared to myeloablative regimens, are safe, and have high engraftment rates with full-donor chimerism in patients having PID, regardless of the specified genetic diagnosis and donor type.

Keywords: Treosulfan; hematopoietic stem cell transplantation; non-myeloablative conditioning; primary immune deficiencies.

MeSH terms

  • Adolescent
  • Busulfan / administration & dosage
  • Busulfan / analogs & derivatives*
  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Deficiency Syndromes / mortality
  • Immunologic Deficiency Syndromes / therapy*
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Male
  • Retrospective Studies
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • treosulfan
  • Busulfan