Acute toxicity and outcome among pediatric allogeneic hematopoietic transplant patients conditioned with treosulfan-based regimens

Pediatr Hematol Oncol. 2020 Aug;37(5):355-364. doi: 10.1080/08880018.2020.1738604. Epub 2020 Mar 13.

Abstract

Treosulfan-based regimens constitute a feasible and increasingly used, but still myeloablative, conditioning in pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the acute toxicity and outcome of all consecutive (2004-2015) pediatric HSCT patients prepared for HSCT with treosulfan in a single-center setting. We included HSCTs performed for both nonmalignant (n = 23) and malignant diseases (n = 11). The controls were patients with nonmalignant diseases or hematological malignancies conditioned with cyclophosphamide (Cy)-total body irradiation (TBI)-based (39 patients) or busulfan-based regimens (11 patients). The major toxicities of the treosulfan-based regimens were limited to oral mucosa and skin. 50% of the patients needed IV morphine for severe mucositis compared to 31% in patients conditioned with Cy-TBI (P = 0.02). Other toxicities were rare. The disease-free survival (DFS) of patients transplanted for nonmalignant disorders was 88.9 ± 7.5% at 2 years. The event-free survival (EFS) at 2 years in this small cohort for those with a malignant disease and a treosulfan-based conditioning was 54.5 ± 1.5%. We conclude that a treosulfan-based conditioning regimen gives excellent DFS in pediatric HSCT performed for a nonmalignant disorder but with substantial mucosal toxicity. In a malignant disorder a treosulfan-based regimen looks promising but larger, preferably randomized, studies are needed to prove efficacy.

Keywords: Allogeneic stem cell transplantation; conditioning regimen; pediatric; treosulfan.

MeSH terms

  • Adolescent
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Busulfan / adverse effects
  • Busulfan / analogs & derivatives*
  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Female
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Male
  • Myeloablative Agonists / adverse effects
  • Myeloablative Agonists / therapeutic use
  • Retrospective Studies
  • Transplantation Conditioning / adverse effects*
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Whole-Body Irradiation / methods

Substances

  • Antineoplastic Agents
  • Myeloablative Agonists
  • Cyclophosphamide
  • treosulfan
  • Busulfan