Four hundred and sixty-seven hematopoietic stem cell transplantations (HSCTs) (217 autologous and 250 allogeneic HSCT) were performed in 374 children at four pediatric HSCT centers in Korea from January 2005 to December 2007. Among 467 transplants, veno-occlusive disease (VOD) developed in 72 transplants (15.4%) at a median of 10 days after HSCT. Multivariate analysis showed that BU or TBI-containing regimen (P ¼ 0.002), VOD prophylaxis without lipo-prostaglandin E1 (PGE1) (P ¼ 0.012), number of previous HSCT (P ¼ 0.014), and pretransplant serum ferritin (P ¼ 0.018) were independent risk factors for developing VOD. Mean serum ferritin levels were significantly higher in HSCT with VOD (2109.6 ± 2842.5 ng/ml) than in HSCT without VOD (1315.9±1094.4 ng/ml) (Po0.001). The relative risk of death within 100 days of HSCT in transplants with VOD compared with transplants without VOD was 3.39 (confidence interval: 1.78-6.45). Our results suggest that lipo-PGE1 might have a protective effect against the development of VOD, and pretransplant serum ferritin could act as a risk factor for VOD. A larger prospective study is needed to confirm a possible role of lipo-PGE1 and iron chelation therapy in reducing the incidence of VOD.
We evaluated the feasibility of T-cell-depleted haploidentical hematopoietic SCT (HHCT) in pediatric patients. Between July 2008 and January 2013, 28 patients underwent ex vivo T-cell-depleted HHCT; 9 had hematologic malignancy, 18 had nonmalignant hematologic disease, and 1 had refractory neuroblastoma. Twenty-six patients achieved neutrophil engraftment at a median of 11 days (range, 9-15 days). Two patients failed to achieve primary engraftment and five experienced graft rejection after primary engraftment. These seven patients achieved stable engraftment after a second HHCT. The cumulative incidences (CIs) of ⩾ grade II and ⩾ grade III acute GVHD were 33.3% and 14.3%, respectively, and the 1-year CI of extensive chronic GVHD was 11.1%. Four patients died of non-relapse-related causes (two of CMV disease, one of encephalopathy and one of autoimmune hemolytic anemia) and one of leukemia relapse. Non-relapse mortality at 100 days, 1 year and 2 years was 0.0%, 10.7% and 14.3%, respectively. At a median follow-up of 32.8 months (range, 17.0-72.5 months), the 2-year OS was 82.1%. OSs for nonmalignant diseases and malignant diseases were 94.4% and 60.0%, respectively (P = 0.019). Thus, HHCT is a realistic alternative for patients with malignant or nonmalignant diseases who lack a suitable donor.Bone Marrow Transplantation (2015) 50, 225-231; doi:10.1038/bmt.2014.232; published online 13 October 2014 INTRODUCTION Recent advances in haploidentical hematopoietic SCT (HHCT) have improved outcomes and enabled the use of haploidentical relatives as donors for children and adults with diseases that are curable with hematopoietic cell transplantation (HCT).A recently developed transplant strategy using a CD3/CD19-depleted graft instead of CD34 + cell selection has shown improved results. [1][2][3] Depleting CD3 + cells is superior to selecting CD34 + cells in terms of rapid engraftment and immune reconstitution. 2,3 Depletion of CD3 + T cells also has the advantage of increasing the number of natural killer cells, monocytes and other immunomodulating cells. 4 We recently completed our prospective study of in vitro CD3-depleted HHCT for pediatric patients lacking suitable related or unrelated donors. We reported our experience with CD3-depleted HHCT for patients with acquired SAA and patients with graft failure (GF) after allogeneic HCT. 5,6 These patients constitute part of the current patient cohort: of 28 patients in the present cohort, 17 were included in the previous two reports. The purpose of the present study was to assess the efficacy and feasibility of CD3-depleted HHCT in the children and adolescents of our cohort with an additional 11 patients and with an extended follow-up of previously reported cases.
Graft failure (GF) is a significant complication after allogeneic hematopoietic stem cell transplantation (HCT) and is associated with a high mortality rate. We performed re-transplantation using haploidentical-related donors to rescue children with early GF. Between 2008 and 2013, 10 patients received re-transplantation from haploidentical family donors. The median age at HCT was 13.5 years and the median time between transplantations was 52.5 days. Conditioning regimen with fludarabine and CY was used in seven patients, and TBI was added in three patients. All 10 patients received T-cell-depleted grafts using CD3 or CD3/CD19 MoAb. The median numbers of CD34 þ and CD3 þ cells were 5.52 Â 10 6 /kg and 1.08 Â 10 6 /kg, respectively. For GVHD prophylaxis, mycophenolate mofetil (MMF) and tacrolimus or MMF and CYA were used. All 10 patients achieved a sustained neutrophil engraftment and maintained a complete donor chimerism at the time of analysis (median 23 months, range 6-62 months). Nine of 10 patients were alive, and one patient with moyamoya disease with AML died of encephalopathy 7 months post transplant. This study suggests that fludarabine-and CY-based conditioning with T-cell-depleted haploidentical HCT is a feasible option to rescue pediatric patients with primary GF. Keywords: pediatric; graft failure; haploidentical hematopoietic stem cell transplantation INTRODUCTION Graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) is associated with a high mortality. The overall frequency of GF under myeloablative conditioning has been reported to be o5%. Meanwhile, it reaches around 10% for haploidentical HCT (HHCT) and umbilical cord blood transplantation (UCBT).1-3 Following GF, a second transplantation offers the best opportunity for long-term, disease-free survival for these patients. However, the best conditioning regimen and the optimal stem cell source for salvage transplantation are yet to be determined, and achieving stable engraftment is often difficult with engraftment rates as low as 30%.4 Waki et al. 5 reported the results of salvage UCBT. Although more than half of the patients achieved neutrophil engraftment, transplant-related mortality (TRM) at day 100 was 45, and 60% of the deaths were related to infectious complications, with the probability of 1-year OS at 33%. On the other hand, second transplantation using haploidenticalrelated donors showed more favorable results. 6,7 We performed salvage transplantation using T-cell-depleted grafts from haploidentical-related donors to rescue children and adolescents with early GF after initial transplantation, and in this study, we report the results.
Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ + T-cell-depleted graft with targeted αβ cells at 1-5 × 10 5 /kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾ grade II and ⩾ grade III acute GvHD were 31 ± 7.1% (SE) and 12 ± 5.0%, respectively, and 1-year CI of chronic GvHD was 15 ± 5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6 ± 2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88 ± 11.7 and 50 ± 10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ + T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor. While αβ + T cells are known to be associated with the initiation of GvHD, γδ + T cells can enhance immune reconstitution and are not implicated in GvHD. 6 Recently, we reported our experience with HHCT using a CD3-depleted graft. 7 Since 2012, we have initiated HHCT using ex vivo depletion of αβ + T cells with targeted αβ cells at 1-5 × 10 5 /kg after add-back. Here, we report our prospective results using αβ-depleted grafts in HHCT for children and adolescents with malignant or non-malignant disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.