Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes

Abstract

Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.57 x 10(7)/kg) because of the patients' young age (median, 1.5 years) and small size (median, 12 kg). Median follow-up was 4.2 years (range, 1-11 years). The cumulative incidences of neutrophil and platelet engraftment were 87.1% (95% confidence interval [CI], 81.8%-92.4%) and 71.0% (95% CI, 63.7%-78.3%). A total of 97% achieved high (> 90%) donor chimerism. Serum enzyme normalized in 97% of patients with diseases for which testings exist. Grade III/IV acute GVHD occurred in 10.3% (95% CI, 5.4%-15.2%) of patients. Extensive chronic GVHD occurred in 10.8% (95% CI, 5.7%-15.9%) of patients by 1 year. OS at 1 and 5 years was 71.8% (95% CI, 64.7%-78.9%) and 58.2% (95% CI, 49.7%-66.6%) in all patients and 84.5% (95% CI, 77.0%-92.0%) and 75.7% (95% CI, 66.1%-85.3%) in patients with high (80-100) performance score. In multivariate analysis, favorable factors for OS were high pretransplantation performance status, matched donor/recipient ethnicity, and higher infused colony forming units.

Figure 1

Probability of engraftment, GVHD, and OS, and the impact of certain patient characteristics. (A) Probability of neutrophil engraftment. (B) Probability of platelet engraftment (50 000). (C) Probability of grades II to IV aGVHD, grades III to IV aGVHD, and cGVHD. (D) Probability of OS. (E) Impact of the donor-patient ethnicity matching on the OS; P = .05 in multivariate analysis. (F) Impact of performance status (80-100 vs < 80) on the OS; P < .001 in multivariate analysis.

Figure 2

Impact of graft characteristics on the probability of engraftment and OS. Probability plots are shown for the each of the 4 quartiles. Panels A, E, and I depict the impact of cryopreserved TNCs (× 10⁷/kg recipient weight) on neutrophil engraftment, platelet engraftment, and OS, respectively. Panels B, F, and J depict the impact of infused TNCs (× 10⁷/kg recipient weight) on neutrophil engraftment, platelet engraftment, and OS, respectively. Panels C, G, and K depict the impact of infused CD34 cells (× 10⁵/kg recipient weight) on neutrophil engraftment, platelet engraftment, and OS, respectively. Panels D, H, and L depict the impact of infused CFUs (× 10⁴/kg recipient weight) on neutrophil engraftment, platelet engraftment, and OS, respectively. P values are shown with each plot for the quartile analysis. Further analyses of the impact of the graft characteristics above and below the median value on the engraftment and OS were conducted and are presented in Tables 2–5, and in the text of the paper.

Figure 3

Disease-specific Kaplan-Meier estimates of the probability of OS.