Journal article
A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support
Background: Maintenance therapy with interferon- after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon- in relation to genetic variation in genes related to inflammation. Design and Methods: In a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon- as maintenance therapy.
We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G for associations with time to treatment failure and overall survival with and without interferon- treatment. Results: The wild type ins-allele of polymorphism NFKB1-94 ins/delATTG was, by multivariate Cox analysis, associated with longer time to treatment failure (p=0.01) and overall survival (p=0.0084) when tested between treatment arms and in the subgroup of patients treated with interferon- the wild type ins-allele was associated with longer overall survival (p=0.002).
In the absence of interferon- treatment, there was no association between the polymorphisms and treatment outcome, except for patients homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-.
Conclusions: Patients who are homozygous carriers of the wild type ins-allele of the NFKB1 -94ins/delATTG polymorphism may benefit from treatment with interferon-, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon- treatment is dependent on the availability of nuclear factor-B and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon- after high-dose therapy.
A prospective study of interferon- treatment in relation to NFKB1 -94ins/delATTG is highly warranted.
| Language: | English |
|---|---|
| Publisher: | Ferrata Storti Foundation |
| Year: | 2009 |
| Pages: | 1274-1281 |
| ISSN: | 15928721 and 03906078 |
| Types: | Journal article |
| DOI: | 10.3324/haematol.2008.004572 |
Adult Aged Alleles CD3 Complex Disease-Free Survival Female Humans IL6 protein, human Immunologic Factors Interferon-alpha Interleukin-1beta Interleukin-6 Male Middle Aged Multiple Myeloma NF-kappa B p50 Subunit NF-κB NFKB1 protein, human Polymorphism, Genetic Stem Cell Transplantation Survival Rate Transplantation, Homologous interferon multiple myeloma polymorphism treatment outcome
