title: Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study.
abstract: Double umbilical cord blood transplantation is increasingly applied in the treatment of adult patients with high-risk hematological malignancies and has been associated with improved engraftment as compared to that provided by single unit cord blood transplantation. The mechanism of improved engraftment is, however, still incompletely understood as only one unit survives. In this multicenter phase II study we evaluated engraftment, early chimerism, recovery of different cell lineages and transplant outcome in 53 patients who underwent double cord blood transplantation preceded by a reduced intensity conditioning regimen. Primary graft failure occurred in one patient. Engraftment was observed in 92% of patients with a median time to neutrophil recovery of 36 days (range, 15-102). Ultimate single donor chimerism was established in 94% of patients. Unit predominance occurred by day 11 after transplantation and early CD4(+) T-cell chimerism predicted for unit survival. Total nucleated cell viability was also associated with unit survival. With a median follow up of 35 months (range, 10-51), the cumulative incidence of relapse and non-relapse mortality rate at 2 years were 39% and 19%, respectively. Progressionfree survival and overall survival rates at 2 years were 42% (95% confidence interval, 28-56) and 57% (95% confidence interval, 43-70), respectively. Double umbilical cord blood transplantation preceded by a reduced intensity conditioning regimen using cyclophosphamide/fludarabine/4 Gy total body irradiation results in a high engraftment rate with low non-relapse mortality. Moreover, prediction of unit survival by early CD4(+) lymphocyte chimerism might suggest a role for CD4(+) lymphocyte mediated unit-versus-unit alloreactivity. www.trialregister.nl NTR1573.
authors.affiliation: Erasmus MC-Daniel Den Hoed Cancer Center, Dept. of Hematology, Rotterdam Sanquin Blood Supply, Dept. of Transfusion Medicine, Rotterdam/Leiden.
authors.forename: Judith A E
authors.initials: JA
authors.lastname: Somers
authors.affiliation: Erasmus MC-Daniel Den Hoed Cancer Center, Dept. of Hematology, Rotterdam.
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.affiliation: Erasmus MC-Daniel Den Hoed Cancer Center, Clinical Trial Center, HOVON Data Center, Rotterdam.
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.affiliation: University Medical Center Utrecht, Dept. of Hematology.
authors.forename: Eefke J
authors.initials: EJ
authors.lastname: Petersen
authors.affiliation: Leiden University Medical Center, Dept. of Hematology.
authors.forename: Erik W A
authors.initials: EW
authors.lastname: Marijt
authors.affiliation: Academic Medical Center, Dept. of Hematology, Amsterdam.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Huisman
authors.affiliation: Sanquin Blood Supply, Dept. of Transfusion Medicine, Rotterdam/Leiden.
authors.forename: Kees
authors.initials: K
authors.lastname: Sintnicolaas
authors.affiliation: Europdonor Foundation, Leiden Leiden University Medical Center, Dept. of Immunohematology and Blood Transfusion, the Netherlands.
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.affiliation: Erasmus MC-Daniel Den Hoed Cancer Center, Clinical Trial Center, HOVON Data Center, Rotterdam.
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Groenendijk-Sijnke
authors.affiliation: Sanquin Blood Supply, Dept. of Transfusion Medicine, Rotterdam/Leiden Europdonor Foundation, Leiden Leiden University Medical Center, Dept. of Immunohematology and Blood Transfusion, the Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.affiliation: Erasmus MC-Daniel Den Hoed Cancer Center, Dept. of Hematology, Rotterdam j.cornelissen@erasmusmc.nl.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D014916:Whole-Body Irradiation; D055815:Young Adult
references.citation: Biol Blood Marrow Transplant. 2007 Jan;13(1):82-9
references.pmid: 17222756
references.citation: Biol Blood Marrow Transplant. 2010 Aug;16(8):1090-8
references.pmid: 20304085
references.citation: Biol Blood Marrow Transplant. 2008 May;14(5):583-90
references.pmid: 18410901
references.citation: Blood. 2011 Mar 24;117(12):3277-85; quiz 3478
references.pmid: 21149633
references.citation: Int J Hematol. 2009 Nov;90(4):526-531
references.pmid: 19697099
references.citation: Clin Cancer Res. 2004 Jun 1;10(11):3586-92
references.pmid: 15173064
references.citation: Bone Marrow Transplant. 2011 May;46(5):659-67
references.pmid: 20697368
references.citation: Bone Marrow Transplant. 2012 Jun;47(6):799-803
references.pmid: 21946383
references.citation: Biol Blood Marrow Transplant. 2011 Sep;17(9):1316-26
references.pmid: 21232625
references.citation: Biol Blood Marrow Transplant. 2013 May;19(5):799-803
references.pmid: 23416850
references.citation: Blood. 2010 Nov 25;116(22):4693-9
references.pmid: 20686119
references.citation: Curr Opin Oncol. 2009 Jun;21 Suppl 1:S31-4
references.pmid: 19561411
references.citation: Leukemia. 2006 Oct;20(10):1690-700
references.pmid: 16871276
references.citation: Blood. 2010 Nov 11;116(19):3999-4006
references.pmid: 20587781
references.citation: Control Clin Trials. 1989 Mar;10(1):1-10
references.pmid: 2702835
references.citation: Blood. 2007 Oct 15;110(8):3064-70
references.pmid: 17569820
references.citation: Blood. 2005 Feb 1;105(3):1343-7
references.pmid: 15466923
references.citation: Clin Exp Immunol. 2010 Oct;162(1):146-55
references.pmid: 20731674
references.citation: N Engl J Med. 2004 Nov 25;351(22):2265-75
references.pmid: 15564543
references.citation: Biol Blood Marrow Transplant. 2012 May;18(5):805-12
references.pmid: 22015993
references.citation: Blood. 2003 Sep 1;102(5):1915-9
references.pmid: 12738676
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D863-9
references.pmid: 19875415
references.citation: Biol Blood Marrow Transplant. 2013 Jun;19(6):904-11
references.pmid: 23416854
references.citation: Leukemia. 2012 Feb;26(2):312-22
references.pmid: 21860431
references.citation: Blood. 2013 Jan 31;121(5):752-8
references.pmid: 23223509
references.citation: Blood. 2014 Jan 2;123(1):133-40
references.pmid: 24141369
references.citation: Biol Blood Marrow Transplant. 2013 Feb;19(2):266-73
references.pmid: 23041604
references.citation: Bone Marrow Transplant. 2013 Jun;48(6):782-6
references.pmid: 23241738
references.citation: Biol Blood Marrow Transplant. 2012 Apr;18(4):565-74
references.pmid: 21875503
references.citation: Blood. 2010 Jan 28;115(4):757-65
references.pmid: 19822900
references.citation: Biol Blood Marrow Transplant. 2010 Apr;16(4):500-8
references.pmid: 19932758
references.citation: Best Pract Res Clin Haematol. 2010 Jun;23(2):275-82
references.pmid: 20837339
references.citation: Int J Hematol. 2006 Jan;83(1):74-9
references.pmid: 16443557
references.citation: Biol Blood Marrow Transplant. 2012 Aug;18(8):1243-9
references.pmid: 22326302
references.citation: Blood. 2009 Nov 5;114(19):4293-9
references.pmid: 19706886
references.citation: Blood. 2012 Jun 7;119(23):5591-8
references.pmid: 22496153
references.citation: Blood. 2006 Oct 15;108(8):2874-80
references.pmid: 16804113
references.citation: Blood. 2010 Mar 4;115(9):1843-9
references.pmid: 20029048
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