Long-Term Outcomes of Reduced-Toxicity Conditioning Using 8-Gray Total Body Irradiation, Fludarabine, and Cyclophosphamide in Children, Adolescents, and Young Adults With Hematological Malignancies

Hematol Oncol. 2025 Jan;43(1):e70026. doi: 10.1002/hon.70026.

Abstract

Recent studies have indicated that total body irradiation (TBI)-based reduced-toxicity conditioning (RTC) may be a potential treatment modality, especially in adults with leukemia. However, its efficacy and safety in children with hematological malignancies remain unclear. To investigate the long-term outcomes and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using an 8-Gray (Gy) TBI/fludarabine (FLU)/cyclophosphamide (CY) RTC in children with hematological malignancies. We included 66 consecutive patients with leukemia, lymphoma, or myelodysplastic syndrome in this retrospective cohort study. Participants were < 25 years old and received an 8-Gy TBI/FLU/CY RTC regimen followed by the first allo-HSCT at Shinshu University Hospital between March 2004 and March 2021. The 5-year overall and relapse-free survival probabilities were 88.2% and 76.5%, respectively, in the lymphoid malignancy group. The myeloid malignancy group had probabilities of 72.4% and 58.6%, respectively. The 5-year cumulative incidences of relapse and non-relapse mortality were 20.6% and 2.9%, respectively, in the lymphoid malignancy group. These incidences were 37.9% and 3.4%, respectively, in the myeloid malignancy group. All patients had engraftment without early relapse and none developed grade 5 regimen-related toxicity within 28 days after allo-HSCT. Nonetheless, two patients had congenital abnormalities caused by chromosomal aberrations and died without relapse. 8-Gy TBI/FLU/CY RTC was safe in children with hematological malignancies, regardless of the donor source. However, safety concerns were noted in cases of chromosomal aberration-induced congenital abnormalities. Additionally, patients in the lymphoid and myeloid malignancy groups had favorable prognoses.

Keywords: 8‐Gy total body irradiation; child; hematological malignancy; reduced‐toxicity conditioning; safety; survival.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Child
  • Child, Preschool
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / adverse effects
  • Cyclophosphamide* / therapeutic use
  • Female
  • Follow-Up Studies
  • Hematologic Neoplasms* / mortality
  • Hematologic Neoplasms* / therapy
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Infant
  • Male
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning* / adverse effects
  • Transplantation Conditioning* / methods
  • Vidarabine* / administration & dosage
  • Vidarabine* / analogs & derivatives
  • Vidarabine* / therapeutic use
  • Whole-Body Irradiation* / adverse effects
  • Young Adult

Substances

  • Cyclophosphamide
  • Vidarabine
  • fludarabine