title: Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency.
abstract: BACKGROUND
  Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy.
  
  
  OBJECTIVE
  We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs.
  
  
  METHODS
  We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66).
  
  
  RESULTS
  Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001).
  
  
  CONCLUSIONS
  Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif. Electronic address: dvorakc@peds.ucsf.edu.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Amel
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.affiliation: Department of Pediatrics, University Medical Center, Ulm, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hönig
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Buckley
authors.affiliation: Division of Hematology and Hematologic Malignancies, Primary Children's Hospital, University of Utah School of Medicine/Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: Hematology/Oncology/BMT Program, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Davis
authors.affiliation: University Children's Hospital, Stem Cell Transplantation Department, Zurich, Switzerland.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Güngör
authors.affiliation: Oncology Department, The Children's Hospital at Westmead, Westmead, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Gabriel
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Bleesing
authors.affiliation: Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Nancy
authors.initials: N
authors.lastname: Bunin
authors.affiliation: Department of Pediatric Hematology and Oncology, Teaching Hospital Motol, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Sedlacek
authors.affiliation: Division of Pediatric Hematology-Oncology, University of Michigan, Ann Arbor, Mich.
authors.forename: James A
authors.initials: JA
authors.lastname: Connelly
authors.affiliation: Department of Pediatrics, University of Oklahoma, Oklahoma City, Okla.
authors.forename: David F
authors.initials: DF
authors.lastname: Crawford
authors.affiliation: Division of Immunology and The Manton Center for Orphan Disease Research, Children's Hospital Boston, Harvard Medical School, Boston, Mass.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: Division of Hematology and Oncology, Boston Children's Hospital, and the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
authors.forename: Jake
authors.initials: J
authors.lastname: Hassid
authors.affiliation: Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
mesh_terms: D000328:Adult; D001315:Australia; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D046528:Chimerism; D005060:Europe; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009656:North America; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D035781:Siblings; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D061349:Unrelated Donors; D014838:Volunteers
keywords: Severe combined immunodeficiency; conditioning; hematopoietic cell transplantation; serotherapy; sibling donors; umbilical cord blood; unrelated donors
references.citation: J Allergy Clin Immunol. 2008 Feb;121(2):361-7
references.pmid: 18086494
references.citation: Blood. 2004 Oct 15;104(8):2475-83
references.pmid: 15217838
references.citation: J Pediatr Hematol Oncol. 2008 May;30(5):396-400
references.pmid: 18458578
references.citation: N Engl J Med. 1999 Feb 18;340(7):508-16
references.pmid: 10021471
references.citation: Blood. 2012 Oct 25;120(17):3615-24; quiz 3626
references.pmid: 22791287
references.citation: Biol Blood Marrow Transplant. 2012 Jan;18(1):141-4
references.pmid: 21801705
references.citation: Bone Marrow Transplant. 2008 Jan;41(2):119-26
references.pmid: 17968328
references.citation: J Allergy Clin Immunol. 2014 Apr;133(4):1092-8
references.pmid: 24290292
references.citation: Blood. 2007 May 15;109(10):4575-81
references.pmid: 17272510
references.citation: Biol Blood Marrow Transplant. 2013 Nov;19(11):1608-14
references.pmid: 24029650
references.citation: Br J Haematol. 2012 Mar;156(5):656-66
references.pmid: 22224700
references.citation: J Allergy Clin Immunol. 2010 Sep;126(3):602-10.e1-11
references.pmid: 20673987
references.citation: J Allergy Clin Immunol. 2013 Apr;131(4):1233-5
references.pmid: 23141738
references.citation: Transplantation. 2004 Feb 27;77(4):526-31
references.pmid: 15084929
references.citation: J Allergy Clin Immunol. 2013 Apr;131(4):994-1000
references.pmid: 23465660
references.citation: Blood. 2012 Mar 22;119(12):2949-55
references.pmid: 22308292
references.citation: J Exp Med. 1987 Apr 1;165(4):1212-7
references.pmid: 3549961
references.citation: J Clin Immunol. 2013 Jan;33(1):96-110
references.pmid: 23001410
references.citation: Blood. 2010 Sep 30;116(13):2229-36
references.pmid: 20530285
references.citation: Blood. 2009 Aug 13;114(7):1445-53
references.pmid: 19433858
references.citation: J Clin Immunol. 2013 Oct;33(7):1156-64
references.pmid: 23818196
references.citation: Biol Blood Marrow Transplant. 2009 Jan;15(1):1-11
references.pmid: 19135937
references.citation: Blood. 1998 May 15;91(10):3646-53
references.pmid: 9573000
references.citation: Pediatr Transplant. 2011 Nov;15(7):E152-5
references.pmid: 20534026
references.citation: J Allergy Clin Immunol. 2009 Dec;124(6):1152-60.e12
references.pmid: 20004776
references.citation: JAMA. 2006 Feb 1;295(5):508-18
references.pmid: 16449616
references.citation: Bone Marrow Transplant. 2005 Feb;35(3):225-31
references.pmid: 15558041
references.citation: Biol Blood Marrow Transplant. 2008 Oct;14(10):1125-1133
references.pmid: 18804042
references.citation: Blood. 2000 Oct 1;96(7):2419-25
references.pmid: 11001893
references.citation: Science. 2007 Nov 23;318(5854):1296-9
references.pmid: 18033883
references.citation: N Engl J Med. 1969 Sep 25;281(13):691-7
references.pmid: 4186068
references.citation: Bone Marrow Transplant. 2001 Apr;27(7):703-9
references.pmid: 11360109
references.citation: Lancet. 2009 Sep 12;374(9693):912-20
references.pmid: 19729196
references.citation: Bone Marrow Transplant. 2005 Aug;36(4):295-9
references.pmid: 15968287
references.citation: J Allergy Clin Immunol. 2013 Jul;132(1):140-50
references.pmid: 23810098
references.citation: J Clin Immunol. 2012 Oct;32(5):1141-4
references.pmid: 22864628
references.citation: Bone Marrow Transplant. 1995 Aug;16(2):289-95
references.pmid: 7581150