Haploidentical Hematopoietic Stem Cell Transplantation for Paediatric Patients with X-linked Lymphoproliferative Syndrome.

The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival.

Sequential haplo-identical conditioning transplant regimen for pediatric patients with relapsed or refractory hemophagocytic lymphohistiocytosis.

Allogeneic hematopoietic stem cell transplantation (HSCT) currently stands as the sole remedy for individuals afflicted with hemophagocytic lymphohistiocytosis (HLH). In this study, we retrospectively evaluated how pediatric patients with relapsed or refractory (R/R) HLH responded to our institution's cocktail conditioning regimen. The disease was diagnosed according to criteria applicable to patients with familial/genetic, relapsing, or severe/persistent HLH. All donors were HLA haplo-identical family donors. In our cohort, sixty-five patients (P-HLH), including 28 with familial/genetic HLH, 36 with secondary HLH, and 1 with an unknown cause, underwent haplo-identical family donor HSCT. The conditioning regimen consisted of intravenous administration of etoposide (VP-16), busulfan, fludarabine, rabbit anti-human thymocyte globulin (r-ATG), and cyclophosphamide (Cy). Tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GvHD) prevention. We observed that the median time for neutrophil recovery was 11 days (range, 8-24), and for platelet counts to exceed 20 × 109/L, it was 14 days (range, 7-130). There were 5 patients (7.7%) who experienced grades III to IV acute GvHD, and 6 patients (9.2%) developed extensive chronic GvHD. The estimated 3- and 5-year overall survival rates were 78.1% (95% CI, 65.8-84.6%) and 74.9% (95% CI, 61.2-84.4%), respectively. The estimated 3- and 5-year event-free survival rates were 73.5% (95% CI, 60.8-82.6%) and 70.3% (95% CI, 56.4-80.5%), respectively. Our findings demonstrate that our innovative conditioning regimen is both effective and safe, offering valuable insights for healthcare professionals evaluating the merits of existing therapies.

Second Allogeneic Hematopoietic Stem Cell Transplantation for Hemophagocytic Syndrome with Engraftment Failure.

This study aims to assess the efficacy of second allogeneic hemopoietic stem cell transplantation (allo-HSCT) for treating hemophagocytic syndrome with first engraftment failure. Among a total of 35 patients who underwent allo-HSCT between June 2015 and July 2021 for HLH, 10 patients who underwent a second HSCT following graft rejection were retrospectively analyzed. Various factors, such as the treatment course and outcome, the remission status, donor selection, and the conditioning regimen of patients before second allo-HSCT, were scrutinized for transplant-related complications and transplant-related mortality, as well as transplant outcomes. All the subjects have achieved complete donor engraftment, in which the neutrophils and platelets engraftment occurred in a median time of 12 d (range 10-19 d) and 24 d (range 11-97 d), respectively. Among the selected subjects, 20% of patients are diseased due to transplant-related thrombotic microangiopathy. Further, 90% of patients are diagnosed with aGVHD, in which 3 of them with grade I aGVHD, one patient with grade II aGVHD, two patients with grade III GVHD, and three patients with localized chronic GVHD. Moreover, 70% of patients showed signs of combined viral infections. Despite the complex symptoms, the overall survival rate is around 80%, with transplant-related mortality and the incidence of post-transplant GVHD of 20% and 60%, respectively. Together, our findings indicated that the second allo-HSCT showed great potential in treating hemophagocytic syndrome with engraftment failure.

Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation with Cocktail Conditioning Regimen for the Treatment of Pediatric Patients with Chronic Active Epstein-Barr Virus: A Retrospective Observational Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was considered as an only therapeutic strategy for chronic active Epstein-Barr virus (CAEBV) infection with few exceptions, while efficacy of various allo-HSCT conditioning regimens for CAEBV has not been fully investigated yet. This study aimed to compare the effectiveness of cocktail conditioning regimen (CCR)-allo-HSCT with reduced-intensity conditioning regimen (RICR)-allo-HSCT for pediatric patients with CAEBV. Data of a total of 54 children with CAEBV from July 2015 to December 2020 were retrospectively analyzed. Among them, 32 patients received VP16, total body irradiation (TBI), busulfan, fludarabine, cyclophosphamide, and antithymocyte globulin (ATG) (CCR1 group), 10 patients received VP16, ara-C, TBI, busulfan, fludarabine, cyclophosphamide, and ATG (CCR2 group), and the remaining 12 patients received VP16, busulfan or melphalan, fludarabine, and ATG with or without ara-C (RICR group). The overall survival (OS), hematopoietic engraftment, the incidence of severe graft-versus-host disease, and other parameters were analyzed. After adjusting for potential confounders, CCR1 (hazard ratio [HR]: 0.023; 95% confidence interval [CI]: 0.001-0.448; P < 0.02) and CCR2 (HR: 0.028; 95% CI: 0.002-0.457; P < 0.02) were associated with a longer OS than RICR. The use of CCR could markedly improve the engraftment success rate and OS rate compared with RICR for pediatric patients with CAEBV.

Autologous cord blood transplantation in children with acquired severe aplastic anemia.

OBJECTIVE: To investigate the efficacy of ACBT for acquired SAA in children. METHODS: Four patients including three girls and one boy were diagnosed with acquired SAA. Their ages were 5, 3, 1, and 3 years, respectively. Patients received an immunoablative preparative regimen using low-dose antithymocyte globulin, cyclophosphamide, and fludarabine. The unrelated human umbilical cord MSC were infused before the autologous cord blood was transfused on day 0. The first and second patients were not treated with immunosuppressive agents after transplantation. The third and the fourth patients received cyclosporine A for half a year after transplantation followed by a 6-month taper. RESULTS: Initial hematopoietic reconstitution was seen in all the four patients. There was no association between engraftment time and the number of total cells and CD34+ cells. Relapse was seen in the first case about half a year after the transplantation. The other three patients with durable hematopoietic reconstitution are with good quality of life. No GVHD was observed. CONCLUSIONS: Three of four patients maintained prolonged hematopoiesis following an immunosuppressive-based preparative regimen and infusion of autologous cord blood cells. It is recommended that cyclosporine be maintained for 6 months after transplantation. ACBT could be considered for acquired SAA if available.

Ascorbic acid-2-o-phosphate-6-o-palmitate protecting the human umbilical cord vein endothelial cells against hydrogen peroxide and tert-butyl hydroperoxide induced cytotoxicity.

Reactive oxygen species are believed to play a role in the development of several diseases including vascular diseases and the aging process. It is reported that increased reactive oxygen species were implicated as an important mechanism that contributes to endothelial dysfunction. So, human umbilical cord vein endothelial cells were used to study the antioxidative effect of L-ascorbic acid and its derivative. The study indicated that L-ascorbic acid as a traditional antioxidant was instable and could protect the cells against hydrogen peroxide induced cytotoxicity as its concentration below 50 microg/ml, but hardly could protect the cells against tert-butyl hydroperoxide induced cytotoxicity. Ascorbic acid-2-o-phosphate-6-o-palmitate could effectively protect the cells against hydrogen peroxide and tert-butyl hydroperoxide induced cytotoxicity, and exhibited no cytotoxicity within the tested concentration range. The study indicated that ascorbic acid-2-o-phosphate-6-o-palmitate could not only significantly reduce the intracellular reactive oxygen species level in 3 h culture, but also increase the cell viability in 15 h culture. In addition, ascorbic acid-2-o-phosphate-6-o-palmitate could keep stable in RPMI-1640 medium and water for 4 days, permeate the cell membrane, which in turn may scavenge the intracellular reactive oxygen species, increase the cell viability and the plasminogen activators'activity. All the above results suggested that addition of some hydrophobic groups to the traditional antioxidants could form novel compounds with better properties.