A Multi-Institutional Retrospective Data Analysis of Hematopoietic Cell Transplantation for Less Severe Sickle Cell Disease

Abstract

Methods: Pediatric patients (<21 years old, n¼34) 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/ml was 16.5 v. 22.1 days in patients receiving expanded cells or not, respectively (p¼0.026). The mean duration of initial hospitalization was 43.2 v. 55.6 days (p¼0.05) (Fig. 1), mean duration for continuous opiate medications 9.7 v. 18.1 days (p¼0.07), and mean time receiving TPN was 20.7 v. 30.1 days (p¼0.06) (Fig. 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.

Haematopoietic stem cell transplantation for sickle cell disease – current practice and new approaches

“…Improving outcomes have altered the risk‐benefit ratio of HSCT leading to the reconsideration of indications that are more age‐based and incorporate additional disease complications and/or donor source. (Walters, ; Dioguardi et al , ; Angelucci et al , ). Nonetheless, the existing indications have expanded the number of patients eligible for HSCT, capitalizing on improved HSCT outcomes that have made the risk versus benefit more favourable.…”

Hematopoietic stem cell transplant referral patterns for children with sickle cell disease vary among pediatric hematologist/oncologists’ practice focus: A Sickle Cell Transplant Advocacy and Research Alliance (STAR) study

“…Recent improvements in HSCT outcomes for children with severe SCA has generated interest in extending HSCT to less severely affected children with SCA and non‐SCA genotypes in the United States, Canada, and other countries where access to optimal supportive care is more readily available 11–14 . At some centers, HSCT is now being offered to children with less severe disease 15 . However, the referral practice for HSCT is widely variable and not enough children with SCD are being offered HSCT 7,16,17 …”

“…[11][12][13][14] At some centers, HSCT is now being offered to children with less severe disease. 15 However, the referral practice for HSCT is widely variable and not enough children with SCD are being offered HSCT. 7,16,17 The Respondents were given a series of scenarios and asked to rate their likelihood of referring for MSD HSCT using a Likert scale (1 = very unlikely, 5 = very likely).…”