title: B-cell function after unrelated umbilical cord blood transplantation using a minimal-intensity conditioning regimen in patients with X-SCID.
abstract: Patients with X-linked severe combined immunodeficiency (X-SCID) suffer from severe and persistent infections, and usually die early in life unless treated by hematopoietic stem cell transplantation. If a patient has an HLA-identical sibling donor, preparative conditioning is not necessary for T-cell engraftment and B-cell function. However, in the absence of such a donor, long-term reconstitution of full B-cell function is often problematic, leading in many cases to a lifetime requirement for immunoglobulin replacement therapy. Preparative myeloablative conditioning has been shown to improve long-term B-cell function, but may aggravate pre-existing infection and transplant-related toxicity. It is thus important to determine the minimum intensity of conditioning that assures immunoglobulin production. In the present study, we performed reduced-intensity conditioning (RIC), consisting of fludarabine 125 mg/m(2) and melphalan 80 mg/m(2), prior to unrelated umbilical cord blood transplantation (UCBT) for five patients with X-SCID, none of them had an HLA-identical donor. Four patients survived more than 4 years without sequelae, and none required long-term immunoglobulin replacement therapy. One patient succumbed to sepsis in conjunction with severe GVHD. Our result demonstrates that the RIC regimen described above in combination with UCBT is an effective and less toxic conditioning to correct B-cell function in patients with X-SCID.
authors: Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo Machi, Aoba-ku, Sendai, 980-8574, Japan, kumaki@med.tohoku.ac.jp.
authors: Satoru
authors: S
authors: Kumaki
authors: Yoji
authors: Y
authors: Sasahara
authors: Yoshiro
authors: Y
authors: Kamachi
authors: Hideki
authors: H
authors: Muramatsu
authors: Tomohiro
authors: T
authors: Morio
authors: Kumiko
authors: K
authors: Goi
authors: Kanji
authors: K
authors: Sugita
authors: Tomonari
authors: T
authors: Urabe
authors: Hidetoshi
authors: H
authors: Takada
authors: Seiji
authors: S
authors: Kojima
authors: Shigeru
authors: S
authors: Tsuchiya
authors: Toshirou
authors: T
authors: Hara
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000276:immunology*; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D053632:X-Linked Combined Immunodeficiency Diseases / Q000276:immunology* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D006680:HLA Antigens; D007136:Immunoglobulins; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
references: Bone Marrow Transplant. 2001 Jul;28(1):101-3
references: 11498753
references: Int J Hematol. 2012 Dec;96(6):773-80
references: 23132596
references: Int J Legal Med. 2007 Mar;121(2):85-9
references: 16642351
references: J Pediatr. 2009 Dec;155(6):834-840.e1
references: 19818451
references: Br J Haematol. 2011 Aug;154(3):363-72
references: 21569009
references: Immunol Rev. 2005 Feb;203:98-109
references: 15661024
references: JAMA. 2006 Feb 1;295(5):508-18
references: 16449616
references: J Allergy Clin Immunol. 2010 Apr;125(4):790-7
references: 20371393
references: Blood. 1999 Oct 15;94(8):2923-30
references: 10515898
references: Lancet. 2009 Sep 12;374(9693):912-20
references: 19729196
references: Blood. 2012 Mar 22;119(12):2949-55
references: 22308292
references: Bone Marrow Transplant. 2005 Feb;35(4):323-34
references: 15543194
references: Blood. 2005 Jan 15;105(2):879-85
references: 15367433
references: Lancet. 2003 Feb 15;361(9357):553-60
references: 12598139
references: Bone Marrow Transplant. 2007 Oct;40(7):633-42
references: 17660844
references: J Allergy Clin Immunol. 2012 Mar;129(3):597-604; quiz 605-6
references: 22277203