Phase II trial of parathyroid hormone after double umbilical cord blood transplantation

Abstract

Transplantation of 1 or 2 umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in each infusion results in slow engraftment. In mouse models, administration of parathyroid hormone (PTH) is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced-intensity double umbilical cord blood transplantation, followed by PTH at 100 μg/day for 28 days. Thirteen patients (median age, 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment of >20 × 10(9) cells/L was 30 days and 61 days, respectively. The incidence of grade II-IV acute GVHD was 38.5% at day 100. Four deaths occurred before day 100, prompting early study closure. No patient who received a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62%, and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery.

Trial registration: ClinicalTrials.gov NCT00393380.

Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Neutrophil and Platelet Engraftment.

Figure 2

Overall Survival and Disease-Free Survival.

Figure 3

T cell receptor excision circles (TREC) levels. TREC counts per microgram PBMC DNA were determined by quantitative PCR. The line connects the average values of the individual time points. The limit of detection of the TREC assay was 10 copies / ug DNA. The dashed line to the far right shows range of values for 10 normal controls of similar ages.