Unrelated donor transplants Outcomes of unrelated cord blood transplantation in pediatric recipients J Styczynski 1,2 , Y-K Cheung 3 , J Garvin 1 , DG Savage 4 , GB Billote 1 , L Harrison 1 , D Skerrett 5 , K Wolownik 1 , C Wischhover 1 , R Hawks 1 , MB Bradley 1 , G Del Toro 1 , D George 1 , D Yamashiro 1 , C van de Ven 1 and MS Cairo 1 1 Department of Pediatrics, Children’s Hospital of New York-Presbyterian, Herbert Irving Comprehensive Cancer Center, USA; 2 Department of Pediatric Hematology and Oncology, Medical University Bydgoszcz, Poland; 3 Department of Biostatistics, Columbia University, New York, NY, USA; 4 Department of Medicine, Columbia University, New York, NY, USA; and 5 Department of Pathology, Columbia University, New York, NY, USA Summary: We report results of unrelated cord blood transplants (UCBT) in 29 pediatric recipients in one center and the risk factors associated with survival. Median age: 9 years (0.5–20); diagnosis: ALL (9), AML (4), CML (1), HD (3),HLH(1),NHL(3),NBL(2);B-thal(1),FA(1),FEL (1), Krabbe (1), WAS (1), SAA (1); median follow-up: 11 months; conditioning: total body irradiation (TBI)-abla- tive (14), chemotherapy-ablative (6) and reduced intensity chemotherapy (9); GVHD prophylaxis: MMF/FK506 (18), cyclosporin A (CsA) þ steroids7MMF (7) or CsA þ methotrexate (MTX) (4); median total nucleated cells (TNC): 3.8  10 7 /kg (1.1–11); median CD34 þ : 2.3  10 5 /kg (0.2–9.9); and HLA match: 2 (6/6), 5 (5/ 6), 22 (4/6). Neutrophil engraftment by cumulative incidence curves 63% (median 28 (95% confidence interval (CI) 18–32)). Probability of Xgrade II acute graft-versus-host disease (aGVHD) by day þ 60 27%, Xgrade III aGVHD 20% and chronic graft-versus-host disease 3%. Estimated 1-year overall survival (OS) 46% (95% CI 30–71) and standard risk 60% (95% CI 29– 100%). Variables associated with improved survival by multivariate analysis include non-TBI-ablative condition- ing(P ¼ 0.024), CD34 þ /kg(P ¼ 0.038) and gender (P ¼ 0.048). These results suggest that CD34/kg cell dose and non-TBI-ablative conditioning may be important variables influencing OS following UCBT in pediatric recipients. Giventhesmallnumberofpatients,theseresultsshouldbe viewed cautiously. Bone Marrow Transplantation (2004) 34, 129–136. doi:10.1038/sj.bmt.1704537 Published online 26 April 2004 Keywords: UCBT; non-TBI conditioning; CD34 cell dose; GVHD; ablative conditioning Unrelated cord blood (UCB) has been successfully used as an alternative source of allogeneic hematopoietic stem cells for patients with hematologic and nonhematologic malig- nant diseases, bone marrow failure syndromes, hemo- globinopathies, immunodeficiencies and inborn errors of metabolism. 1–6 Transplantation of unrelated allogeneic UCB progenitor cells is now considered to be as effective as that of unrelated bone marrow progenitor cells for children and some adults for whom conventional methods of therapy failed. By July 2002, total worldwide resources of cryopreserved cord blood included over 80000 cryopre- served units and approximately 2058 UCB transplants (UCBT) have been reported to date (1510 children and 546 adults). 7,8 The clinical advantages of UCBT are rapid availability, shorter time of donor search, lower risk of transmission of viral infectious diseases, reduced immuno- logical reactivity, lower risk and severity of acute (AGVHD) and chronic (CGVHD) graft-versus-host dis- ease, and possibly allowing greater degree of HLA mismatching between donor and recipient. 2–7 Compared with hematopoietic stem cells from adults, hematopoietic stem cells in cord blood have distinctive proliferative advantages including the capacity to form increased colonies in ex vivo culture systems, a higher cell cycle rate, autocrine production of growth factors and longer telo- meres. 9,10 There are only a few studies describing the results of a large cohort of UCBTs performed in one center. 2,3,11 The majority of reports of UCBT are from cord blood bank registries or cord blood banks. 5,12,13 However, in a large single center experience at the University of Minnesota, Wagner et al reported results of transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases. 2 The main objective of this study is to report the outcomes, namely, hemato- logical recovery, GVHD, transplantation-related mortality and overall survival (OS) of unrelated cord blood transplants in children performed in one center over the last 5 years. Our secondary objective is to determine risk factors associated with survival. Received 19 June 2003; accepted 22 February 2004 Published online 26 April 2004 Presented in part at the Tandem BMT Meeting, ASBMT, Keystone, Colorado, January 2003 Correspondence: Professor MS Cairo, Division of Pediatric Hematology and Blood and Marrow Transplantation, Children’s Hospital of New York – Presbyterian, Columbia University, 161 Fort Washington Ave., Irving 7, New York, NY 10032, USA; E-mail: mc1310@columbia.edu Bone Marrow Transplantation (2004) 34, 129–136 & 2004 Nature Publishing Group All rights reserved 0268-3369/04 $30.00 www.nature.com/bmt