Revised International Prognostic Index and genetic alterations are associated with early failure to R-CHOP in patients with diffuse large B-cell lymphoma
Por:
Dlouhy, I, Karube, K, Enjuanes, A, Salaverria, I, Nadeu, F, Ramis-Zaldivar, JE, Valero, JG, Rivas-Delgado, A, Magnano, L, Martin-Garcia, D, Perez-Galan, P, Clot, G, Rovira, J, Jares, P, Balague, O, Gine, E, Mozas, P, Briones, J, Sancho, JM, Salar, A, Mercadal, S, Alcoceba, M, Valera, A, Campo, E, Lopez-Guillermo, A
Publicada:
1 feb 2022
Ahead of Print:
1 oct 2021
Resumen:
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) cases have a poor outcome. Here we analysed clinico-biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, mutational status of 106 genes was studied by targeted next-generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39. Ninety-seven cases (26%) were identified as EF and showed significantly shorter overall survival (OS). Patients with B symptoms, advanced stage, high levels of serum lactate dehydrogenase (LDH) or beta 2-microglobulin, low lymphocyte/monocyte ratio and higher Revised International Prognostic Index (R-IPI) scores, as well as those with BCL2 rearrangements more frequently showed EF, with R-IPI being the most important in logistic regression. Mutations in NOTCH2, gains in 5p15 center dot 33 (TERT), 12q13 (CDK2), 12q14 center dot 1 (CDK4) and 12q15 (MDM2) showed predictive importance for EF independently from R-IPI. GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over-representation of gene sets related to extra-cellular matrix and tumour microenvironment.
Filiaciones:
Dlouhy, I:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Portugues Oncol Francisco Gentil, Dept Hematol, Lisbon, Portugal
Karube, K:
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Univ Ryukyus, Cell Biol & Pathol Dept, Grad Sch Med, Nishihara, Okinawa, Japan
Enjuanes, A:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Salaverria, I:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Nadeu, F:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Ramis-Zaldivar, JE:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Valero, JG:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Rivas-Delgado, A:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Magnano, L:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Martin-Garcia, D:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Perez-Galan, P:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Clot, G:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Rovira, J:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Jares, P:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Balague, O:
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Gine, E:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Mozas, P:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Briones, J:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Sancho, JM:
ICO Hosp Germans Trias & Pujol, Badalona, Spain
Salar, A:
Hosp del Mar, Barcelona, Spain
Mercadal, S:
ICO Hosp Duran & Reynals, Lhospitalet De Llobregat, Spain
Alcoceba, M:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Hosp Clin Univ, Salamanca, Spain
Valera, A:
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Campo, E:
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain
Univ Barcelona, Barcelona, Spain
Lopez-Guillermo, A:
Hosp Clin Barcelona, Dept Hematol, Villarroel St 170, Barcelona 08036, Spain
Ctr Invest Biomed Red Canc CIBERONC, Tumores Hematol, Madrid, Spain
Univ Barcelona, Barcelona, Spain
|