Faculty Collaboration Database

Single nucleotide polymorphisms in the NOD2/CARD15 gene are associated with an increased risk of relapse and death for patients with acute leukemia after hematopoietic stem-cell transplantation with unrelated donors. J Clin Oncol 2007 Sep 20;25(27):4262-9

Date

08/29/2007

Pubmed ID

17724347

DOI

10.1200/JCO.2007.12.1897

Scopus ID

2-s2.0-34948899807 (requires institutional sign-in at Scopus site)   52 Citations

Abstract

PURPOSE: Hematopoietic stem cell transplantation (HSCT) is an important option in the management of acute leukemia, but the risk of disease relapse and death remains appreciable. Recent studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2)/caspase recruitment domain 15 (CARD15) gene single nucleotide polymorphisms (SNPs), implicated in innate immunity and Crohn's disease, may also affect immune function post-HSCT.

PATIENTS AND METHODS: NOD2/CARD15 genotypes were analyzed in 196 patients diagnosed with acute leukemia and their unrelated donors. The pairs are part of a previously well-characterized cohort with a median follow-up of 2.2 years (range, 0.42 to 6.61 years). T-cell depletion was used in 83% of pairs.

RESULTS: NOD2/CARD15 SNPs were associated with a reduction in overall survival (44% v 22%; log-rank P = .0087) due to an increase in disease relapse (32% v 54%; Gray's test P = .001) as compared with wild-type pairs. In multivariate analyses, the two most significant factors impacting outcome were transplantation in relapse and the presence of SNPs. The incidence of acute graft-versus-host disease was low and there was no significant difference due to the presence of SNPs.

CONCLUSION: These data indicate an unrecognized role for the NOD2/CARD15 gene in unrelated donor HSCT for acute leukemia. The increased risk of disease relapse suggests that the wild-type gene product may contribute to a graft-versus-leukemia effect. These data suggest that NOD2/CARD15 genotyping before transplantation may contribute to prognosis and influence clinical management.

Author List

Mayor NP, Shaw BE, Hughes DA, Maldonado-Torres H, Madrigal JA, Keshav S, Marsh SG

Author

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Child
Child, Preschool
Cohort Studies
Female
HLA Antigens
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Leukemia, Myeloid, Acute
Male
Middle Aged
Nod2 Signaling Adaptor Protein
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence