The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy.

Autor: Holte H; Department of Oncology, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for B cell malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway., Beiske K; Department of Pathology, Oslo University Hospital, Oslo, Norway., Boyle M; Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada., Trøen G; Department of Pathology, Oslo University Hospital, Oslo, Norway., Blaker YN; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Myklebust J; KG Jebsen Centre for B cell malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Kvaløy S; Department of Surgery, Vestfold Hospital Trust, Oslo, Norway., Rosenwald A; Institute of Pathology, University of Würzburg and Comprehensive Cancer Centre (CCC) Mainfranken, Würzburg, Germany., Lingjaerde OC; Department of Informatics, University of Oslo, Oslo, Norway., Rimsza LM; Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA., Smeland EB; KG Jebsen Centre for B cell malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Scott DW; Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada., Kolstad A; Department of Oncology, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2018 Oct; Vol. 183 (2), pp. 225-234. Date of Electronic Publication: 2018 Aug 06.
DOI: 10.1111/bjh.15518
Abstrakt: Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high-dose therapy with autologous stem cell support has resulted in 10-year overall survival (OS) higher than 60%. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression-based proliferation signature, Ki-67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring-based RNA expression-based proliferation assay (MCL35) on formalin-fixed paraffin-embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy-four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low-, intermediate- and high-risk categories. MCL35 low- and intermediate- risk groups had overlapping progression-free survival (PFS), while patients in the high-risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI-C (MIPI with the addition of binary Ki67 score +/-30%) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI-C scores can identify patients who still have a dismal outcome despite intensified treatment.
(© 2018 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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