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• Unlicensed umbilical cord blood units can be safely and effectively used for hematopoietic cell transplantation (HCT) in adult and pediatric patients. • Unlicensed umbilical cord blood expands access to racially/ethnically diverse patients in need of HCT. • Further studies are required to compared licensed and unlicensed umbilical cord blood HCT. Umbilical cord blood (UCB) transplantation (UCBT) is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access to transplantation for non-Caucasian patients unable to find a fully matched unrelated donor. In 2011, the US Food and Drug Administration required that unrelated UCBT be performed using either licensed UCB or unlicensed UCB under the Investigational New Drug (IND) program. The National Marrow Donor Program manages an IND under which 2456 patients (1499 adults and 957 children, 564 with malignant diseases and 393 with nonmalignant diseases) underwent single or double UCBT between October 2011 and December 2016. The median patient age was 31 years (range, <1 to 81 years), and 50% of children and 36% of adults were non-Caucasian. The median time to neutrophil engraftment (ie, absolute neutrophil count ≥500/mm3) was 22 days for adults, 20 days for pediatric patients with malignant diseases, and 19 days for pediatric patients with nonmalignant diseases, with corresponding rates of engraftment at 42 days of 89%, 88%, and 90%. In these 3 groups of patients, the incidence of acute graft-versus-host disease (GVHD) grade II-IV was 35%, 32%, and 24%; the incidence of chronic GVHD was 24%, 26%, and 24%; and 1-year overall survival (OS) was 57%, 71%, and 79%, respectively. In multivariate analysis, younger age, lower Hematopoietic Cell Transplantation-Specific Comorbidity Index, early-stage chemotherapy-sensitive disease, and higher performance score were predictive of improved OS for adults. In a subset analysis of children with malignancies undergoing single UCBT, the use of either licensed UCB (n = 48) or unlicensed UCB (n = 382) was associated with similar engraftment and survival. The use of unlicensed UCB units is safe and effective and provides an important graft source for a diverse population. [ABSTRACT FROM AUTHOR]

Abstract: In an attempt to abrogate the deleterious effects of graft-versus-host disease (GVHD), allogeneic transplantation for nonmalignant diseases was performed using high-dose CD34-cell infusion, partial T cell depletion, and no posttransplantation GVHD prophylaxis. Between 1998 and 2004, 16 patients with matched related donors were treated. Median age was 1.5 years (range, 5 months-18 years). The conditioning regimen consisted of busulphan 16 mg/kg, cyclophosphamide 200 mg/kg, antithymocyte globulin (ATG) 25 mg/kg, and fludarabine 200 mg/m2. No GVHD prophylaxis was given. High doses of CD34 cells, positively selected by immunomagnetic beads, were infused at a median dose of 10.7 × 106 CD34/kg (range, 7.4-50 × 106). A total of 1 × 105/kg T cells were given. All patients engrafted, with no graft rejections. All were alive and well at a median of 37 months posttransplantation (range, 18-89 months). Only 1 patient developed chronic GVHD. No episodes of severe infection occurred during or after transplantation. Immunologic reconstitution with CD3/CD4 T cells > 200/μL was observed at a median of 117 days and that with naive T cells (CD4/CD45RA) at a median of 188 days posttransplantation. Our findings suggest that allogeneic transplantation from a matched family donor for nonmalignant disorders can be successfully performed using high doses of CD34 cells, moderate T cell depletion, and no posttransplantation immunosuppression. [Copyright &y& Elsevier]

Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases in children. However, patients frequently have significant morbidity before transplantation and there is a high transplant-related mortality. Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from different stem cell sources. All patients were conditioned with fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of tacrolimus and methotrexate with additional prednisolone for haploidentical grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. Five of the six are alive and in complete disease resolution at a median of 19 months (range, 7–53 months) after SCT. One patient died of bacteremia before engraftment. Three patients achieved complete donor chimerism. Two patients remained stable mixed chimerism. Short-term toxicities were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine-based nonmyeloablative regimen followed by SCT provides a good approach for children with nonmalignant diseases. Even patients with severe organ dysfunctions had adequate engraftment with acceptable toxicities.Bone Marrow Transplantation (2006) 38, 665–669. doi:10.1038/sj.bmt.1705511; published online 2 October 2006 [ABSTRACT FROM AUTHOR]