Results of the Cord Blood Transplantation Study (COBLT): Outcomes of Unrelated Donor Umbilical Cord Blood Transplantation in Pediatric Patients with Lysosomal and Peroxisomal Storage Diseases

Abstract

The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, is a phase II multicenter study designed to evaluate the use of cord blood in allogeneic transplantation. In this report, we evaluated the outcomes of cord blood transplantation in 69 patients with lysosomal and peroxisomal storage diseases. Patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3) were enrolled between August 1999 and June 2004. All patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7 x 10(7)/kg. One-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days. Grade II to IV acute GVHD occurred in 36% of patients. Cord blood donors are readily available for rapid transplantation. Cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases.

Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure

“…The 'alive and engrafted' rates in this paper are similar to published data 10,11 as others have noted, 10,19 TCD was a risk factor for graft failure. In the study by Souillet et al, 11 16/27 patients received a mismatched graft (1-4 mismatches) with no documented higher incidence of graft failure or GvHD.…”

Long-Term Functional Outcomes of Children with Hurler Syndrome Treated with Unrelated Umbilical Cord Blood Transplantation

“…The safety and efficacy of UCBT from unrelated donors was similar to that reported by previous studies (Staba et al 2004;Martin et al 2006;Prasad et al 2008). However, this is the only comprehensive prospective longitudinal study on a large cohort of patients with Hurler syndrome who were evaluated before and after transplanta- Fig.…”

“…Neurodevelopmental Assessment All patients underwent comprehensive neurodevelopmental examinations using standardized and validated neurobehavioral tools, and outcomes were compared to norms of typically developing children (Martin et al 2006). Age equivalents were used to allow comparison across tests and determine the acquisition of new skills.…”

“…There is evidence of improved neurocognitive outcomes after umbilical cord blood transplantation (UCBT) in children with Hurler syndrome, adrenoleukodystrophy, and Krabbe disease, particularly when performed early in the disease course (Staba et al 2004;Escolar et al 2005;Beam et al 2007;Prasad et al 2008). Various studies of UCBT in Hurler syndrome patients report high rates of sustained engraftment with full donor chimerism and normal IDUA activity (Staba et al 2004;Martin et al 2006;Prasad et al 2008). Furthermore, umbilical cord blood is readily available, reducing the time between diagnosis and transplantation, which is important for optimal prognosis (Staba et al 2004;Escolar et al 2005).…”

Emerging trends in transplantation of inherited metabolic diseases

“…[1][2][3][4][5][6][7][8][9][10] Recent reports from European and American collaborative studies suggest that there is growing acceptance of this form of therapy. 3,11,12 In this report, we review the published literature using HSCT to treat IMD and also review recent results of umbilical cord blood transplantation for this indication. In addition, we define the current status of the field, the scientific basis for efficacy of transplantation therapy, areas of debate, and future directions.…”