Background: Cord blood transplant (CBT) recipients have delayed hematopoietic recovery compared to recipients of other stem cell sources following allogeneic transplant. Prolonged neutrophil (ANC) recovery, in particular, places these patients at risk of protracted mucositis, extended hospitalization and increased risk of infection-related morbidity and mortality. To mitigate these risks, we have developed a methodology for generating increased absolute numbers of cord blood (CB) hematopoietic stem/progenitor cells (HSPC) by culture of the CB HSPC in the presence of Notch ligand, cryopreserving the final harvested product, and subsequently administering the product as an adjunct cellular therapy to patients receiving CBT. This has resulted in significantly decreased time to neutrophil recovery following CBT1. Here we evaluated whether administration of these cells impacted duration of hospitalization, use of opiate pain medications, and requirement for total parenteral nutrition (TPN) or infectious outcomes during initial hospitalization for CBT. Methods: Pediatric patients (<21 years old, n=34) on a research protocol between 4/2006 and 6/2014 receiving myeloablative conditioning (FLU/CY/13.2 Gy TBI) with or without expanded CB HSPC (fresh or cryopreserved) were included. Duration of initial hospitalization, use of opiate pain medications (by continuous infusion or PCA), and use of TPN were determined for each patient. All blood stream infections occurring during initial hospitalization were also recorded. Statistical comparisons between groups were made with two-tailed, unpaired t-tests. Results: 11 patients received expanded CB HSPC in addition to 1-2 unmanipulated CB units while a concurrent cohort of 23 patients received the same conditioning regimen without expanded cell infusion. The mean time to neutrophil count of 500/µl was 16.5 v. 22.1 days in patients receiving expanded cells or not, respectively (p=0.026). The mean duration of initial hospitalization was 43.2 v. 55.6 days (p=0.05) (Fig1), mean duration for continuous opiate medications 9.7 v. 18.1 days (p=0.07), and mean time receiving TPN was 20.7 v. 30.1 days (p=0.06) (Figure 2). Although not statistically significant, bacterial blood stream infections were identified during their initial hospitalization in 3 patients receiving expanded CB HSPC compared to 10 in the standard treatment group. Conclusions: In addition to reduce time to ANC recovery, these results suggest that administration of expanded CB HSPC may significantly reduce initial hospitalization and may also reduce utilization of pain medications and nutritional support in the pediatric population receiving CBT. Thus, this cellular therapy has the potential to decrease the risk of morbidity and mortality post-CBT by reducing regimen related toxicities that directly result from delayed hematopoietic recovery.
Novartis , advisor: chair, data safety monitoring board
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