Interleukin-1 α Genotype and Outcome of Unrelated Donor BMT for CML
| Autor: | Stella M. Davies, Parinda A. Mehta, James Elliott, Daniel J. Weisdorf, Effie W. Petersdorf, Michelle D. Combs, Tiffany A. Wilke, Richard Aplenc, Mary Eapen, Sharavi Gandham, John P. Klein, Margaret L. MacMillan |
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| Rok vydání: | 2005 |
| Předmět: | |
| Zdroj: | Blood. 106:2057-2057 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v106.11.2057.2057 |
| Popis: | IL-1α is a pro-inflammatory cytokine implicated in initiation and maintenance of graft versus host disease (GVHD) and the immune response to infection. A cytosine (C) to thymine (T) transition at codon -889 is believed to influence gene transcription. Previously we showed that the presence of at least one IL-1α T allele in the donor was associated with improved survival after unrelated donor (URD) BMT (survival at 1 year 40% C/C donor, 68% T/C donor, 75% T/T donor, p 18 years) with CML transplanted in first chronic phase between 1990 and 2002 with a cyclophosphamide/TBI preparative regimen. Patients receiving peripheral blood stem cells, a second transplant, or a graft with > 1 HLA antigen mismatch were excluded. Donors and recipients were genotyped for the IL-1α polymorphism using a high throughput PCR assay. Donor recipient pairs were categorized into 4 groups according to the presence or absence of a T-allele in donor and in recipient (only recipient has T-allele, only donor has T-allele, both have T-allele and neither have a T-allele). Median patient age was 38 years (range 18–59); 57% were male; median donor age was 38 years (range 18–57 years) and 64% were HLA-matched at 6 antigens. Genotype categories were not significantly different in recipient and donor age, gender, year of transplant, performance status, GVH prophylaxis, HLA-match, interval from diagnosis to transplant, CMV serology and donor-recipient sex match. The impact of IL-1a genotype on univariate outcomes is shown below. Table 1 Endpoint Recipient has T-allele Donor has T-allele Both have T-allele Neither have T-allele p-value TRM @ 1 yr 41% 43% 43% 43% 0.99 Acute GVHD 64% 67% 68% 72% 0.80 Chronic GVHD 50% 57% 52% 52% 0.81 Relapse@1yr 7% The data show no impact of IL-1α genotype on survival or TRM. Multivariate analysis including donor and recipient age, performance status, year of transplant, CMV status, HLA disparity and donor patient sex mismatch confirmed that IL-1α genotype did not impact survival, LFS, GVHD or TRM. Survival (and LFS) was significantly reduced in recipients of marrow with an allele or antigen level HLA-mismatch (RR 1.9, 95% CI 1.4–2.7; p< 0.0001) and T-depleted marrow (RR 1.43, 95% CI 1.07–1.92; p=0.017). Relapse was notably increased in recipients of T-cell depleted grafts (RR 4.1 95%CI 1.79–9.37; p=0.0008) and TRM increased in recipients of an allele or antigen mismatched graft (RR 2.05 95% CI 1.44–2.91; p< 0.0001). In conclusion these data from a large and relatively homogeneous population do not support a role for IL-1α genotype on outcome of unrelated donor transplant for CML. |
| Databáze: | OpenAIRE |
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