title: Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units.
abstract: Umbilical cord blood (UCB) transplantation is potentially curative for acute leukemia. This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative UCB transplantation. Acute leukemia patients (n = 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center. Patients received a UCB graft composed of either 1 (47%) or 2 (53%) partially human leukocyte antigen (HLA)-matched unit(s). Conditioning was with cyclophosphamide and total body irradiation with or without fludarabine. The incidence of relapse was 26% (95% confidence interval [CI], 19%-33%). In multivariate analysis, relapse was higher in advanced disease patients (> or = third complete remission [CR3]; relative risk [RR], 3.6; P < .01), with a trend toward less relapse in recipients of 2 UCB units (RR = 0.6; P = .07). However, relapse was lower for CR1-2 patients who received 2 UCB units (RR 0.5; P < .03). Leukemia-free survival was 40% (95% CI, 30%-51%) and 51% (95% CI, 41%-62%) for single- and double-unit recipients, respectively (P = .35). Although it is known that transplantation in CR1 and CR2 is associated with less relapse risk, this analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units. This trial was registered at http://clinicaltrials.gov as NCT00309842.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA. verneris@umn.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.forename: Claudio G
authors.initials: CG
authors.lastname: Brunstein
authors.forename: Juliet
authors.initials: J
authors.lastname: Barker
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.forename: David H
authors.initials: DH
authors.lastname: McKenna
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Burke
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Philip B
authors.initials: PB
authors.lastname: McGlave
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult
references.citation: Blood. 2007 Feb 1;109(3):1322-30
references.pmid: 17038536
references.citation: Biol Blood Marrow Transplant. 2008 Dec;14(12):1341-7
references.pmid: 19041055
references.citation: N Engl J Med. 1998 Nov 26;339(22):1565-77
references.pmid: 9828244
references.citation: Blood. 2005 Feb 1;105(3):1343-7
references.pmid: 15466923
references.citation: Blood. 2007 Feb 1;109(3):926-35
references.pmid: 17003380
references.citation: Bone Marrow Transplant. 2004 Jun;33(11):1097-105
references.pmid: 15094744
references.citation: N Engl J Med. 1996 Jul 18;335(3):157-66
references.pmid: 8657213
references.citation: Science. 2004 Aug 13;305(5686):1000-3
references.pmid: 15310902
references.citation: Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10119-22
references.pmid: 7479737
references.citation: N Engl J Med. 1997 Aug 7;337(6):373-81
references.pmid: 9241126
references.citation: Blood. 2001 May 15;97(10):2962-71
references.pmid: 11342418
references.citation: Nature. 2003 Oct 23;425(6960):841-6
references.pmid: 14574413
references.citation: Biol Blood Marrow Transplant. 2007 Jan;13(1):82-9
references.pmid: 17222756
references.citation: Blood. 2007 Dec 15;110(13):4576-83
references.pmid: 17785583
references.citation: J Clin Oncol. 2009 Jan 10;27(2):256-63
references.pmid: 19064984
references.citation: Biol Blood Marrow Transplant. 2006 Sep;12(9):919-27
references.pmid: 16920557
references.citation: Blood. 2007 Oct 15;110(8):3064-70
references.pmid: 17569820
references.citation: Stat Med. 1997 Apr 30;16(8):901-10
references.pmid: 9160487
references.citation: Blood. 2005 Oct 15;106(8):2693-9
references.pmid: 15976178
references.citation: Biol Blood Marrow Transplant. 2002;8(7):368-76
references.pmid: 12171483
references.citation: Bone Marrow Transplant. 1995 Jun;15(6):825-8
references.pmid: 7581076
references.citation: N Engl J Med. 2004 Nov 25;351(22):2265-75
references.pmid: 15564543
references.citation: Exp Hematol. 2003 Dec;31(12):1142-6
references.pmid: 14662319
references.citation: Blood. 2003 Dec 15;102(13):4290-7
references.pmid: 12920027
references.citation: Oncologist. 2007 Mar;12(3):341-55
references.pmid: 17405900
references.citation: Blood. 2009 Mar 12;113(11):2410-5
references.pmid: 18997171
references.citation: Curr Opin Immunol. 2006 Oct;18(5):571-5
references.pmid: 16895752
references.citation: Blood. 2002 Sep 1;100(5):1611-8
references.pmid: 12176879
references.citation: Haematologica. 2006 Feb;91(2):223-30
references.pmid: 16461307
references.citation: Blood. 1999 Jun 1;93(11):3662-71
references.pmid: 10339472
references.citation: Exp Hematol. 2004 Apr;32(4):397-407
references.pmid: 15050751
references.citation: Cytotherapy. 2004;6(4):311-7
references.pmid: 16146883
references.citation: Blood. 1990 Feb 1;75(3):555-62
references.pmid: 2297567
references.citation: Lancet. 2007 Jun 9;369(9577):1947-54
references.pmid: 17560447
references.citation: N Engl J Med. 2001 Jun 14;344(24):1815-22
references.pmid: 11407342
references.citation: N Engl J Med. 2004 Nov 25;351(22):2276-85
references.pmid: 15564544