%0 Journal Article %1 vangsted_polymorphism_2009 %A Vangsted, Annette J %A Klausen, Tobias W %A Gimsing, Peter %A Andersen, Niels F %A Abildgaard, Niels %A Gregersen, Henrik %A Vogel, Ulla %D 2009 %J Haematologica %K Adult, Aged, Alleles, Antigens, B Cell Factors, Female, Genetic, Homologous Humans, Immunologic Interferon-alpha, Interleukin-1beta, Interleukin-6, Male, Middle Multiple Myeloma, Polymorphism, Rate, Stem Subunit, Survival Survival, Transplantation, p50 {CD3}, {Disease-Free} {NF-kappa} %N 9 %P 1274--1281 %R 10.3324/haematol.2008.004572 %T 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 %U http://www.ncbi.nlm.nih.gov/pubmed/19734419 %V 94 %X BACKGROUND Maintenance therapy with interferon-alpha 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-alpha in relation to genetic variation in genes related to inflammation. DESIGN AND METHODS In a retrospective study of 296 patients with multiple myeloma undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha 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-alpha 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-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha 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-alpha. CONCLUSIONS Patients who are homozygous carriers of the wild type ins-allele of the NFKB1 -94ins/delATTG polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear factor-kappaB and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to NFKB1 -94ins/delATTG is highly warranted.

@article{vangsted_polymorphism_2009, abstract = {{BACKGROUND} Maintenance therapy with interferon-alpha 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-alpha in relation to genetic variation in genes related to inflammation. {DESIGN} {AND} {METHODS} In a retrospective study of 296 patients with multiple myeloma undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha 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-alpha 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-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha 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-alpha. {CONCLUSIONS} Patients who are homozygous carriers of the wild type ins-allele of the {NFKB1} {-94ins/delATTG} polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear {factor-kappaB} and the polymorphism in {NFKB1} may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to {NFKB1} {-94ins/delATTG} is highly warranted.}, added-at = {2011-06-24T11:21:47.000+0200}, author = {Vangsted, Annette J and Klausen, Tobias W and Gimsing, Peter and Andersen, Niels F and Abildgaard, Niels and Gregersen, Henrik and Vogel, Ulla}, biburl = {https://www.bibsonomy.org/bibtex/2b6171017d787666d4bce30edafe56df0/ag_vogel}, doi = {10.3324/haematol.2008.004572}, interhash = {5cb3def56eec4257b8b3f4f51786d3a1}, intrahash = {b6171017d787666d4bce30edafe56df0}, issn = {1592-8721}, journal = {Haematologica}, keywords = {Adult, Aged, Alleles, Antigens, B Cell Factors, Female, Genetic, Homologous Humans, Immunologic Interferon-alpha, Interleukin-1beta, Interleukin-6, Male, Middle Multiple Myeloma, Polymorphism, Rate, Stem Subunit, Survival Survival, Transplantation, p50 {CD3}, {Disease-Free} {NF-kappa}}, month = sep, note = {{PMID:} 19734419}, number = 9, pages = {1274--1281}, timestamp = {2011-06-24T11:21:52.000+0200}, title = {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}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19734419}, volume = 94, year = 2009 }