title: Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match.
abstract: Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: D M
authors: DM
authors: Ponce
authors: A
authors: A
authors: Gonzales
authors: M
authors: M
authors: Lubin
authors: H
authors: H
authors: Castro-Malaspina
authors: S
authors: S
authors: Giralt
authors: J D
authors: JD
authors: Goldberg
authors: A M
authors: AM
authors: Hanash
authors: A
authors: A
authors: Jakubowski
authors: R
authors: R
authors: Jenq
authors: E B
authors: EB
authors: Papadopoulos
authors: M A
authors: MA
authors: Perales
authors: M R M
authors: MR
authors: van den Brink
authors: J W
authors: JW
authors: Young
authors: F
authors: F
authors: Boulad
authors: R J
authors: RJ
authors: O'Reilly
authors: S
authors: S
authors: Prockop
authors: T N
authors: TN
authors: Small
authors: A
authors: A
authors: Scaradavou
authors: N A
authors: NA
authors: Kernan
authors: C E
authors: CE
authors: Stevens
authors: J N
authors: JN
authors: Barker
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019819:Budesonide / Q000627:therapeutic use; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D006680:HLA Antigens; D019653:Myeloablative Agonists; D019819:Budesonide; D019703:Calcineurin; D009173:Mycophenolic Acid