Successful rescue of early graft failure in pediatric patients using T-cell-depleted haploidentical hematopoietic SCT

Abstract

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.

Second allogeneic hematopoietic cell transplantation for graft failure: Poor outcomes for neutropenic graft failure

“…Survival rates ranging from 36 – 80% are described[7, 9, 15, 27–30]. In our analysis, neither a donor type nor a specific conditioning regimen led to superior outcomes after the 2nd HCT, though this was confounded by the variability in diagnoses, conditioning regimens and graft sources used.…”

“…The reported outcomes after second HCT are wide-ranging, with overall survival from 11 – 70%[7–17]. To date, no study has examined outcomes of second HCT based upon NGF versus NNGF.…”

Intensive Care Unit Admissions Among Children After Hematopoietic Stem Cell Transplantation

“…Engraftment failure is a significant complication after allogeneic HSCT and is associated with a high mortality rate. 18 Patients suffer from prolonged pancytopenia and immunosuppression, and this condition is often fatal, usually due to overwhelming infection. 19 TA-TMA is a complication consisting of microangiopathic hemolytic anemia and renal/neurological dysfunction associated with high mortality.…”

Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature

“…Several case series of successful salvage therapy after graft failure employing various chemotherapy regimens and donor sources describe variable survival rates ranging from 31 – 80% 18–34 reported in Table 3. In the largest published data set, the CIBMTR reported 122 patients with NGF between the ages of 2 – 61 years (median 30 years), undergoing second HCT after primary graft failure, reporting a low overall survival (OS) rate of 11%, a high 1-year post HCT TRM of 86% (95% CI, 79 – 92), and 1-year relapse rate of 7% (95% CI, 2 – 12) 23 .…”