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.
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