Allogenic peripheral stem cell transplantation from HLA-matched related donors for adult sickle cell disease: remarkable outcomes from a single-center trial.

Adult patients with sickle cell disease (SCD) are highly susceptible to stem cell transplant complications, including drug toxicity, graft versus host disease (GVHD), and graft rejection due to SCD-related tissue damage, endothelial activation, and inflammation. The scarcity of compatible stem cells for transplantation further limits treatment options, with only 43 cases of adult allogeneic peripheral blood stem cell transplantation (allo-PSCT) from human leukocyte antigen (HLA)-identical sibling donors reported in the international registry for the period 1986-2013. Herein we report remarkable outcomes in a cohort of adult SCD patients who underwent allo-PSCT using a fludarabine (Flu), busulfan (Bu), and anti-T-cell lymphocyte globulin (ATG)-based conditioning regimen in combination with very low dose total body irradiation (TBI), followed by post-transplant cyclophosphamide (Cy) and sirolimus as GVHD prophylaxis. We performed a single-center, retrospective study consisting of 20 consecutive patients (mean age 33.4 years) who underwent allo-PSCT from HLA-matched related donors with a conditioning regimen of Flu 150/Bu 3.2/Cy 29/ATG 30 (Fresenius)/TBI 200 between September 2013 and September 2017. Data were validated by an independent data audit group of the affiliated JACIE-accredited transplantation center. All patients experienced a sustained donor cell engraftment. Full donor chimerism (total cell) occurred within 180 days in all patients. Mean duration of follow-up was 13.8 months (range: 0.3-50 months), with 12 (60%) patients completing 12 months. No non-relapse mortality or graft rejection occurred. Successful treatment was achieved without the presence of graft loss, grade III-IV acute GVHD, extensive chronic GVHD, or other major complications. Allo-PSCT in combination with Flu 150/Bu 3.2/Cy 29/ATG 30(Fresenius)/TBI 200- Cy/Sirolimus therapy yielded encouraging outcomes with no mortality and low incidence of GVHD. Further controlled studies will be necessary to compare transplant protocols and long-term outcomes.

The effect of rosiglitazone in the prevention of intra-abdominal adhesion formation in a rat uterine horn model.

BACKGROUND: Effects of rosiglitazone in the prevention of adhesion formation were evaluated. METHODS: Eighty Wistar albino rats were randomly grouped into eight equally sized groups. A 2-cm segment of the antimesenteric surface of the right uterine horn was traumatized to form a standardized lesion, using bipolar cautery. A dose-response study was performed with 0.1, 0.3, 1 and 3 mg/kg/day rosiglitazone. Fifteen days later, adhesions were evaluated clinically and histopathologically. A time-response study was performed with 1 mg/kg/day rosiglitazone (the minimum dose found to significantly affect adhesion formation). Rosiglitazone was given for 7 days post-operatively and results were compared with those of control and the 15-day group (time-response). In all these studies, rosiglitazone was orally administered 3 days before the operation and continued post-operatively. In two further experimental groups, rosiglitazone was only administered pre-operatively or post-operatively. RESULTS: Approximately 1 mg/kg/day rosiglitazone was found to reduce adhesion scores both clinically and histopathologically. Duration of treatment was also found to affect the extent of adhesion formation. However, giving rosiglitazone either just pre-operatively or post-operatively did not significantly reduce adhesion formation. CONCLUSION: Rosiglitazone with peroxisome proliferator-activated receptor (PPAR)-gamma agonist activity reduced the formation of i.p. adhesion possibly by reducing the initial inflammatory response and the subsequent exudation in this study.