Searching for alternative hematopoietic stem cell donors for pediatric patients

Rocha, Vanderson; Locatelli, Franco

doi:10.1038/sj.bmt.1705963

Cited by 148 publications

(116 citation statements)

References 51 publications

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“…Although the speed of neutrophil engraftment was not significantly associated to the occurrence of IFI, very early engraftment (o14 days) may impact outcomes, as may the use of combined CB/haploidentical transplants. 24 Furthermore, as we performed a retrospective risk factor analysis, a prospective study to confirm our results is warranted.…”

Section: Discussionmentioning

confidence: 91%

Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients

Hol

Wolfs

Bierings

et al. 2013

Bone Marrow Transplant

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This study was aimed at finding predictors of invasive fungal infection (IFI) after pediatric allogeneic hematopoietic SCT (HSCT). All children who received allogeneic HSCT in the Wilhelmina Children's Hospital Utrecht between 2004 and 2012 were included. HSCT data were prospectively collected. Patients were retrospectively classified into high-or low-risk groups for developing IFI using criteria based on available literature. Predictors for the occurrence of IFI were analyzed using Cox regression models. We used logistic regression models to analyze the association between other HSCT-related complications and IFI. Secondary outcomes were overall survival and treatment-related mortality (TRM). Two-hundred nine patients were included in the analysis; median age was 6.6 years. The cumulative incidence of IFI was 12%. In patients classified as 'low risk' (n ¼ 75), only 5.3% developed IFI (odds ratio (OR): 0.325; P ¼ 0.047). In multivariate analysis, a predictor for the occurrence of IFI was an a priori determined HSCT TRM risk 420% (based on EBMT-risk score). Post-HSCT, the administration of high-dose steroids was associated with IFI (OR: 4.458; P ¼ 0.010). Patients who developed IFI showed an increased risk of TRM (OR: 3.773; P ¼ 0.004). These results confirm that risk group stratification should guide intensity of monitoring for IFI and use of antifungal prophylaxis.

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Section: Discussionmentioning

confidence: 91%

Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients

Hol

Wolfs

Bierings

et al. 2013

Bone Marrow Transplant

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“…4 Unrelated cord blood transplantation (UCBT) has been explored as an alternative option for patients without a suitable human leukocyte antigen (HLA)-matched donor. 5 Tolerance of some degree of HLA mismatch, with relatively low rates of both acute and chronic graft versus host disease (GvHD), makes UCBT an attractive option for children. 6 Comparable probability of leukemia-free survival (LFS) has been reported in children with acute leukemia receiving either unrelated allele-matched bone marrow transplantation (BMT) or 1 or 2 loci mismatched UCBT.…”

Section: Introductionmentioning

confidence: 99%

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

et al. 2012

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To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) ¼ 0.4, P ¼ 0.01) and for those transplanted in CR1 and CR2 (HR ¼ 0.3, P ¼ 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P ¼ 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR ¼ 2, P ¼ 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.

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“…The same study revealed a significantly better outcome with lower relapse rates and TRM for centers performing a higher number of haplotransplants. 35,54 A preliminary analysis of our ongoing study with CD3/19 depleted grafts showed a 1y-EFS of 70% for acute leukemias in remission. Patients with active disease at time of transplant had an unfavorable outcome with high relapse rates in most studies.…”

Section: Immune Reconstitution and Trmmentioning

confidence: 99%

Haploidentical SCT in children: an update and future perspectives

Lang

Handgretinger

2008

Bone Marrow Transplant

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Transplantation of haploidentical stem cells has become a well-established approach, which makes a potential donor available for almost all patients. This review focuses on current results and new strategies, especially in pediatric patients with malignant diseases. CD34 þ positive selection was the most common procedure for graft manipulation in the past years, whereas T and B cell depletion is a promising new method. GVHD could herewith be effectively reduced and primary engraftment was reported in 83-100% of patients after transplantation of high stem cell doses. For patients with ALL in remission, diseasefree survival at 3 years ranged between 22 and 48%. TRM, mainly because of viral infections, was improved by the use of reduced-intensity conditioning (which helped to speed up T cell recovery) and by close monitoring of viral loads and prophylactic/preemptive therapy. The role of donor-derived Ag-specific T cells against viral and fungal antigens is currently under investigation. Patients with active disease at the time of transplantation had a poor outcome and several attempts to improve these results are currently evaluated, such as co-infusion of natural killer cells, co-transplantation of MSC, use of new antileukemic drugs and post-transplant immunotherapy.

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Searching for alternative hematopoietic stem cell donors for pediatric patients

Cited by 148 publications

References 51 publications

Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients

Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

Haploidentical SCT in children: an update and future perspectives

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