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

Autor: Joanne Kurtzberg, Vinod K. Prasad, Susan Wood, Maria L. Escolar, Timothy A. Driscoll, Paul Szabolcs, Kristin Page, Adam Medizabal, Paul L. Martin, Sonali Lakshminarayanan, Deborah Semmell, Suhag Parikh, Shelly L. Carter, June Allison
Rok vydání: 2007
Předmět:
Zdroj: Blood. 110:336-336
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v110.11.336.336
Popis: 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 status2.1x105/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 (p5.7x104/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.
Databáze: OpenAIRE
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