Improved Outcome Following Busulfan-Based Conditioning in Children with Functional Neutrophil Disorders Undergoing Hematopoietic Stem Cell Transplant from HLA-Matched Donors

J Clin Immunol. 2023 Oct;43(7):1603-1610. doi: 10.1007/s10875-023-01535-2. Epub 2023 Jun 13.

Abstract

Hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for chronic granulomatous disease (CGD) and leukocyte-adhesion deficiency (LAD), but both diseases have high rates of graft failure in transplant and patients with these diseases are often referred to HSCT with significant comorbidity. The intensity of the conditioning regimen should be balanced between the need to ensure durable engraftment and to minimize toxicity when transplanting young children with infections and organ damage. We report on 26 children transplanted at our institution with CGD and LAD over 24 years. We found a higher incidence of graft failure in patients receiving treosulfan based conditioning for their first transplant. There was no effect of conditioning regimen on overall survival, as all 8 patients that proceeded to a second busulfan-based HSCT were salvaged. We recommend giving patients with CGD and LAD fully myeloablative conditioning with either a busulfan-based regimen or the combination of treosulfan, fludarabine, and thiotepa.

Keywords: Busulfan; CGD; Chronic granulomatous disease; Hematopoietic stem cell transplant; Leukocyte-adhesion deficiency; Treosulfan.

MeSH terms

  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Graft vs Host Disease* / etiology
  • Granulomatous Disease, Chronic* / complications
  • Granulomatous Disease, Chronic* / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Neutrophils
  • Transplantation Conditioning / adverse effects

Substances

  • treosulfan
  • Busulfan