Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature

Abstract

Allogeneic hematopoietic cell transplantation (HCT) effectively treats seeveral non-malignant disorders (NMD) such as selected lysosomal disorders, cerebral adrenoleukodystrophy, and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with NMD who underwent a second allogenic HCT for GF using a non-myeloablative (NMA), low dose busulfan-based regimen. Graft sources for the second transplant included umbilical cord blood, unrelated bone marrow and unrelated peripheral blood stem cells. Median age at time of second HCT was 6.6 years (1.1 – 14.6 years). Fourteen of seventeen patients (82%) achieved engraftment, with a 3-year overall survival of 82% (95% CI, 54–94%). Day 100 transplant related mortality was 12% (95% CI, 0–27%). CMV and adenovirus reactivation occurred in 30% and fungal infections in 18%. The incidence of grade II-IV acute graft-versus-host disease was 35% (95% CI, 13–58%) with only 6% grade III-IV (95% CI, 0–17%). In summary, we illustrate excellent overall survival and acceptable toxicity using a NMA conditioning regimen for second HCT as salvage therapy for first graft failure in patients with non-malignant conditions.

Risk Factors, Clinical Outcomes, and Cost-of-Care Related to Graft Failure in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients

“…The conditioning regimen used for a particular patient is always discussed extensively and therefore not consistent for patients across the board. Because the conditioning regimen for a second transplant is usually different from the first, this also creates heterogeneity in salvage regimens relative to prior studies by others where consistent regimens were used [8,18]. For this reason, we cannot draw conclusions about specific conditioning regimens other than the comments on RIC and alemtuzumab that were discussed.…”

“…Over the past 20 years, numerous studies have commented on the risk factors and outcomes of GF in HCT patients [2,18]. However, few have focused on the pediatric population, and there is a great need for more contemporary literature.…”