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TP53 mutations iden...
TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
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- Eskelund, Christian W. (författare)
- Copenhagen University Hospital
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- Dahl, Christina (författare)
- Danish Cancer Society
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- Hansen, Jakob W. (författare)
- Copenhagen University Hospital
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- Westman, Maj (författare)
- Copenhagen University Hospital
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- Kolstad, Arne (författare)
- Oslo university hospital
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- Pedersen, Lone B. (författare)
- Copenhagen University Hospital
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- Montano-Almendras, Carmen P. (författare)
- Copenhagen University Hospital
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- Husby, Simon (författare)
- Copenhagen University Hospital
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- Freiburghaus, Catja (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Ek, Sara (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Pedersen, Anja (författare)
- Copenhagen University Hospital
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- Niemann, Carsten (författare)
- Copenhagen University Hospital
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- Raty, Riikka (författare)
- Helsinki University Central Hospital
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- Brown, Peter (författare)
- Copenhagen University Hospital
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- Geisler, Christian H. (författare)
- Copenhagen University Hospital
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- Andersen, Mette K (författare)
- Copenhagen University Hospital
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- Guldberg, Per (författare)
- Danish Cancer Society
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- Jerkeman, Mats (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lymfom - Klinisk forskning,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lymphoma - Clinical Research,Lund University Research Groups,Skåne University Hospital
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- Grønbæk, Kirsten (författare)
- Copenhagen University Hospital
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(creator_code:org_t)
- American Society of Hematology, 2017
- 2017
- Engelska 8 s.
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
- Relaterad länk:
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http://dx.doi.org/10...
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https://ashpublicati...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- TP53
- lymphoma
- chemoimmunotherapy
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Blood
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- Av författaren/redakt...
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Eskelund, Christ ...
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Dahl, Christina
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Hansen, Jakob W.
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Westman, Maj
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Kolstad, Arne
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Pedersen, Lone B ...
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visa fler...
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Montano-Almendra ...
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Husby, Simon
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Freiburghaus, Ca ...
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Ek, Sara
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Pedersen, Anja
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Niemann, Carsten
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Raty, Riikka
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Brown, Peter
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Geisler, Christi ...
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Andersen, Mette ...
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Guldberg, Per
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Jerkeman, Mats
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Grønbæk, Kirsten
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Lunds universitet