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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4318-4327.
Prepublished online as a Blood First Edition Paper on August 21, 2008; DOI 10.1182/blood-2007-06-098020.
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Submitted June 27, 2007
Accepted August 8, 2008
Results of the Cord Blood Transplantation Study (COBLT): Clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies
Joanne Kurtzberg*, Vinod K Prasad, Shelly L Carter, John E Wagner, Lee Ann Baxter-Lowe, Donna Wall, Neena Kapoor, Eva C. Guinan, Stephen A. Feig, Elizabeth L Wagner, and Nancy A Kernan
PBMT Division, Department of Pediatrics, Duke Unviersity Medical Center, Durham, NC, United States
The EMMES Corporation, Rockville, Maryland, United States
Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN, United States
Immunogenetics and Transplantation Laboratory, University of California, San Francisco, San Francisco, CA, United States
Texas Transplant Institute, San Antonio, TX, United States
Research Immunology and Bone Marrow Transplantation, Children's Hospital of Los Angeles, Los Angeles, CA, United States
Pediatric Bone Marrow Transplantation, Dana Farber Cancer Institute, Boston, MA, United States
Pediatric Hematology and Oncology, Mattel Children's Hospital at UCLA, Los Angeles, CA, United States
National Heart Lung and Blood Institute, Bethesda, MD, United States
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States
* Corresponding author; email: kurtz001{at}mc.duke.edu.
Outcomes of unrelated donor cord blood transplantation (UCBT) in 191 hematologic malignancy children (median age and weight - 7.7 years; 25.9 kg) enrolled between February 1999 and September 2003 and given identical cytoreduction, graft-versus-host disease (GvHD) prophylaxis and supportive care were studied (median follow-up 27.4 months) in a prospective Phase II multi-center National Heart, Lung, and Blood Institute sponsored Cord Blood Transplantation Study (COBLT). HLA matching at enrollment was 6/6(n=17), 5/6(n=58), 4/6(n=111) or 3/6 (n=5) by low-resolution molecular typing for HLA-A, -B and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median pre-cryopreservation total nucleated cell (TNC) dose was 5.1x107 TNC/kg (range 1.5-23.7) with 3.9x107 TNC/kg (range 0.8-22.8) infused. The median time to engraftment (ANC>500/mm3 and platelets 50K/uL) were 27 and 174 days. The cumulative incidence (CINC) of neutrophil engraftment by day 42 was 79.9%(95%CI 75.1%-85.2%); acute grades III/IV GvHD by day 100 was 19.5%(95%CI 13.9-25.5); and chronic GvHD at 2 years was 20.8%(95% CI 14.8-27.7). HR matching decreased the probability of severe acute GvHD. The CINC of relapse at 2 years was 19.9%(95%CI 14.8-25.7). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. UCBT from partially HLA-mismatched units can cure many children with leukemias refractory to standard therapy. This study was registered on the clinicaltrials.gov website with registration number NCT00000603.
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