title: NOD2/CARD15 variants are not a risk factor for clinical outcome after nonmyeloablative allogeneic stem cell transplantation.
abstract: Single nucleotide polymorphisms (SNPs) in the innate immunity receptor NOD2/CARD15 have been demonstrated to modulate the outcome of allogeneic hematopoietic stem cell transplantation (SCT). The effect of NOD2/CARD15 polymorphism is reported to be associated with type of donor (sibling or matched unrelated donor) as well as type of conditioning regimen. We reviewed NOD2/CARD15 SNPs in all donor/recipient pairs of 192 consecutive patients who received nonmyeloablative allogeneic SCT at our institution between 2002 and 2006. All patients were treated with fludarabine 30 mg/m(2)/day for 3 days followed by 200 cGy total-body irradiation (TBI) (n = 154) or TBI alone (n = 38) and received grafts from HLA-matched related (n = 132) or unrelated (n = 61) donors. NOD2/CARD15 polymorphisms were observed in 36 of 192 (19%) patients and in 35 of 192 (18%) donors. The incidences of acute and chronic graft-versus-host disease (aGVHD, cGVHD) were 39% and 49%, respectively, in patients with NOD2/CARD15 variants versus 51% and 61% in patients with wild type. The relapse rate at 3 years was 38% in patients with variants and 36% in patients with wild type. The incidence of transplant-related mortality was 22% for patients with variants and 21% for patients with wild type. Overall survival (OS) at 3 years was 56% in patients with variants and 64% in patients with wild-type NOD2/CARD15. There was no significant impact of NOD2/CARD15 mutations on clinical outcome (all P > .05, Kaplan-Meier and Fine and Gray's tests). These data indicate that mutations in the NOD2/CARD15 gene are not a risk factor for clinical outcome in nonmyeloablative allogeneic SCT. Therefore, screening for NOD2/CARD15 polymorphisms in patients or donors does not have additional value in patients undergoing nonmyeloablative SCT.
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. H.M.vanderStraaten@umcutrecht.nl
authors.forename: Hanneke M
authors.initials: HM
authors.lastname: van der Straaten
authors.forename: Martine M
authors.initials: MM
authors.lastname: Paquay
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
authors.forename: Nan
authors.initials: N
authors.lastname: van Geloven
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Cynthia
authors.initials: C
authors.lastname: Huisman
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014740:Vidarabine; C024352:fludarabine