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.

Allogeneic hematopoietic cell transplantation (HCT) effectively treats several non-malignant disorders 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 non-malignant disorders who underwent a second allogenic HCT for GF using a non-myeloablative, low-dose busulfan-based regimen. Graft sources for the second transplant included umbilical cord blood, unrelated bone marrow and unrelated PBSCs. 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 GvHD 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 non-myeloablative conditioning regimen for second HCT as salvage therapy for first GF in patients with non-malignant conditions.

Functional hyposplenism after hematopoietic stem cell transplantation.

Functional hyposplenism is associated with chronic GvHD (cGvHD) following hematopoietic stem cell transplantation (HSCT). We hypothesized that hyposplenism measured by pitted red cell counts in cGvHD was transient and related to the severity of disease. We performed a serial, retrospective review of 36 pediatric post-HSCT patients' pit counts at BC Children's Hospital from 2005 to 2013 and compared those counts with the clinical course of patients with late acute GvHD (aGvHD)/cGvHD. Of the 36 patients, 22 had late aGvHD/cGvHD based on National Institutes of Health consensus criteria. Fourteen of 22 GvHD patients had an abnormal pitted red cell count. Ten of 14 abnormal patients had late acute or overlap GvHD syndrome, primarily gastrointestinal disease. A second cohort was prospectively evaluated in a multicenter adult HSCT biomarker trial. We identified 3 out of 10 control patients who had an abnormal pitted red cell count, 3 out of 10 with classic cGvHD and 5 out of 9 patients with overlap syndrome were abnormal. In both the retrospective and prospective studies, hyposplenism was present in patients without late aGvHD/cGvHD suggesting current guidelines regarding antibiotic prophylaxis against encapsulated bacteria after HSCT need to be re-addressed and abnormal pit counts could be used to guide prophylaxis in all HSCT patients.