63: Outcomes of Unrelated Umbilical Cord Blood Transplantation in 159 Young Patients with Peroxisomal and Lysosomal Storage Disorders at a Single Center

Background: Bone marrow transplantation benefits patients with lysosomal and peroxisomal storage diseases (LSD). Umbilical cord blood (UCB) may be potential graft source for many patients lacking suitable adult donors. We present the outcomes of Unrelated UCB transplantation (UCBT) in a large series of LSD patients from a single center. Methods: Using myeloablative conditioning with busulfan+cyclophosphamide+antithymocyte globulin and graft-versus-host disease (GvHD) prophylaxis with Cyclosporine+methylprednisolone(n = 125) or cyclosporine+cellcept (n = 34), 159 consecutive LSD patients with Hurler, Krabbe, Sanfilippo, Metachromatic Leukodystrophy, Adrenoleukodystrophy, Hunter, and other diagnoses received UCBT at Duke in 1995–2007. CBU from 8 US public banks were screened and those with high-normal enzyme utilized. Organ function and disease specific studies were performed pre- and post-UCBT. KM estimates of engraftment, survival and GvHD probabilities were calculated and multivariate models were analyzed for a variety of graft and patient factors. Results: Sixty-two (39%) were girls; 16.3% minorities; 19.5% CMV seropositive, and 41.5% had a Lansky < 80%. Age was 1.5 yrs(range 0.05–26.3). 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(post-thaw) was 9.7 × 107(2.2–50.4), 7.6 × 107(1.5–32.4), 2.1 × 105(0.4–104.8) and 5.7 × 104(0.0–105.3), respectively. The cumulative incidence neutrophil and platelet engraftment was 87.1% (95%CI 82%-92%) and 71.0% (95%CI 64%-78%) in a median of 22 and 87 days, respectively. The probability of Grade III/IV acute GvHD was 10.3%(95%CI 5%-15%) by day100. Chronic GvHD developed in 26(13–limited). Overall Survival(OS) at 1, 3, and 5 years was 71.8%(95%CI 65%-79%), 62.7%(95%CI 55%-71%) and 58.2%(95%CI 50%-67%), respectively. In multivariate analysis, Lansky 80–100(p < 0.0001), CFU infused >5.7 × 104/kg (p = 0.02), and matched ethnicity(p = 0.05) increased OS. Once engrafted, all but 3 maintained chimerism >90% and all but 4 normalized enzymes. In high performance status(Lansky 80–100) patients, the OS at 1, 3 and 5 years was 88.4%, 83.5%, and 79.5%, respectively. Conclusions: Unrelated Cord blood is an excellent graft source for treatment of LSD patients, particularly when transplantation is performed in early stages. Pre-transplant performance status and post-thaw CFU dosing were highly predictive of overall survival.