Robust Immune Reconstitution Following Hematopoietic Stem Cell Transplantation in Pediatric Patients
Patients received alemtuzumab as part of a reduced intensity condition regimen and demonstrated early immune recovery.
Hematopoietic stem cell transplantation (HSCT) can often serve as a curative therapy for nonmalignant hematologic disorders. Myeloablation in HSCT is often replaced by reduced intensity conditioning to support donor engraftment because reduced intensity conditioning may decrease regimen-related acute toxicity and late complications. Alemtuzumab, a monoclonal antibody directed against CD52, can be used as part of reduced intensity conditioning in HSCT.
According to results from a phase 1/2 trial (ClinicalTrials.gov Identifier: NCT00920972) published in Biology of Blood and Marrow Transplantation, early treatment with alemtuzumab in patients who received HSCT allowed early immune recovery in spite of immune ablation. Additionally, systemic infections tracked immune reconstitution, and infection patterns were similar after transplants from related donors compared with unrelated donors.
In this multicenter trial, 71 patients with nonmalignant disorders and a median age of 2.5 years old underwent marrow or peripheral blood stem cell transplants with a reduced intensity conditioning regimen consisting of alemtuzumab, fludarabine, and melphalan instead of myeloablation. Early administration of alemtuzumab 19 to 21 days prior to transplant was intended to ameliorate lymphodepletion of the graft and decrease the risk of graft rejection.
Researchers assessed the cohort of patients who had a related donor and the cohort of patients who had an unrelated donor at 100 days, 6 months, and 1 year after HSCT. Recovery of natural killer cells in both cohorts showed normalization by day 100. Average CD3, CD4, and CD8 T-lymphocyte levels normalized by 6 months in the related donor cohort and by 1 year in the unrelated donor cohort.
At 6 months and 1 year after HSCT, CD4 and CD8 T-lymphocyte levels were significantly higher in the related donor cohort than in the unrelated donor cohort (P =.014 and P =.025, respectively). CD19 B-cell levels had normalized by day 100 in the related donor cohort but took 1 year to do so in the unrelated donor cohort.
In spite of differences in immune system reconstitution between the 2 cohorts, neither the timing nor the nature of infections differed significantly between the 2 groups. Infections occurred most frequently in the first 100 days following HSCT. All patients were particularly susceptible to bacterial infections in these first 100 days, and the mortality rate from infections was 1.4% at 1 year.
These results suggest a need for close vigilance to prevent bacterial infections in the first 100 days following HSCT and indicate a strong immune reconstitution.
1. Bhatt ST, Bednarski JJ, Berg J, et al. Immune reconstitution and infection patterns after early alemtuzumab and reduced intensity transplantation for nonmalignant disorders in pediatric patients [published online October 12, 2018]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2018.10.008