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• W2552313457 abstract "Abstract Background: Allogeneic bone marrow transplantation from related and unrelated donors leads to improvement in longevity and quality of life due to replacement of missing enzyme and engraftment of donor-derived glial cells in patients with LSD. Recently, unrelated umbilical cord blood transplant (UCBT) has yielded encouraging results but due to the rarity of LSDs, there has never been a large series of patients transplanted at a single center. Methods: Between 1995 and 2007, 159 consecutive LSD patients received unrelated UCBT at Duke after busulfan, cyclophosphamide, and antithymocyte globulin myeloablation. Cyclosporine+methylprednisolone (n=125) or cyclosporine+cellcept (n=34) was given for graft-versus-host disease (GvHD) prophylaxis. Cord blood units from 8 US public banks were screened and the unit with high-normal enzyme was selected. Engraftment, enzyme, organ function, neurodevelopmental, neuroimaging, and neurophysiologic studies were performed pre- and post-UCBT. The probabilities of engraftment, overall survival (OS) and GvHD were estimated. Multivariate models for graft and patient factors were analyzed. Results: Median patient age was 1.5 yrs (range 0.05–26.3); 19.5% were CMV seropositive; and 41.5% had a performance status<80%. The majority of grafts were 5/6 (47%) or 4/6 (46%) by intermediate-res HLA-A and -B and high-res HLA-DRB1. The median (range) cell dose/kg of TNC (pre-cryo), TNC (infused), CD34 (infused) and CFU (infused) was 9.7x107(2.2–50.4), 7.6x107(1.5–32.4), 2.1x105(0.4–104.8) and 5.7x104(0.0–105.3), respectively. ABO and ethnicity matching between donor/graft pairs were 55% and 82%, respectively. The cumulative incidence of 42 day neutrophil and 180 day platelet engraftment (50k) was 87.1% (95%CI 82%–92%) in a median of 22 days and 71.0% (95%CI 64%–78%) in a median of 87 days, respectively. In multivariate analysis, neutrophil and platelet engraftment was favored by (p< 0.05) patient age = 2 years, infused CD34 >2.1x105/kg, and infused CFU >5.7x104/kg. The probability of day+100 Grade III/IV acute GvHD was 10.3% (95%CI 5%–15%). Chronic GvHD developed in 25 (18%), 11 of whom were extensive. OS at 0.5, 1, 3, and 5 years was 79.0% (95%CI 73%–85%), 71.8% (95%CI 65%–79%), 62.7% (95%CI 55%–71%) and 58.2% (95%CI 50%–67%), respectively. In multivariate analysis, performance status 80–100 (p<0.0001), CFU infused >5.7x104/kg (p=0.02) and matched ethnicity (p=0.05) were independently associated with higher OS. In median follow-up of 4.2 years (range 0.2–11.5), all but 3 engrafted patients maintained donor chimerism >90% and all but 4 normalized enzyme level. In patients with high performance status (80–100), the OS at 1, 3 and 5 years was 88.4% (95%CI 79.6%–97.1%), 83.5% (95%CI 73.0%–94.1%) and 79.5% (95%CI 66.9%–92.1%), respectively. Conclusions: Unrelated Cord blood is an excellent graft source for treatment of patients with these fatal disorders, particularly when transplantation is performed in early stages. Pre-transplant performance status and post-thaw CFU dosing were highly predictive of overall survival." @default.
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• W2552313457 date "2007-11-16" @default.
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• W2552313457 title "Analysis of the Cellular Components of the Graft and Clinical Characteristics of 159 Children with Lysosomal and Peroxisomal Disorders (LSD) Undergoing Unrelated Umbilical Cord Blood Transplantation at a Single Center." @default.
• W2552313457 doi "https://doi.org/10.1182/blood.v110.11.336.336" @default.
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