Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma that without treatment rapidly leads to death. Addition of monoclonal CD20 antibody rituximab (R) to cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine and prednisone (CHOP) chemotherapy has clearly improved survival of patients with DLBCL, and now 74% of the patients receiving immunochemotherapy are reported to remain event free in 6-year follow-up. However, extranodal DLBCL, especially primary testicular (PT) DLBCL, primary central nervous system (CNS) DLBCL, renal/adrenal DLBCL, and according to some earlier reports also sinonasal tract (SNT) DLBCL, have worse prognosis than DLBCL in general. In addition, the impact of the addition of R on the survival of specific subgroups, like PT-DLBCL and SNT DLBCL is not clear. In this study the clinicopathological presentation and impact of the addition of R on the survival of the patients with SNT and PT-DLBCL was analysed. SNT and PT-DLBCL have also been considered to have high risk for CNS spread. To prevent CNS spread, CNS-directed therapy (iv high-dose methotrexate or iv cytarabine) is added for patients with high risk for CNS spread. However, the significance of CNS-directed chemotherapy on SNT and PT-DLBCL patients is unclear and this study aimed to explore it. The clinical data and samples of SNT lymphoma patients treated at the Helsinki University Hospital (Helsinki, Finland) and SNT DLBCL patients also from Tampere University Hospital (Tampere, Finland) were collected and the outcomes in response to different treatment modalities were compared. The present study shows the incidence of SNT lymphoid malignancies is slowly increasing, and that nasopharynx is the most common location in the SNT area. Majority (43%) of the patients had DLBCL, whereas 18% had plasmocytoma. SNT DLBCL patients receiving R and CNS-directed therapy in addition to CHOP-like therapy had longer survival than patients not receiving these as part of their therapy, and the patients receiving both R and CNS- directed therapy as part of their therapy had the longest survival. PT-DLBCL patients were chosen here to present another extranodal patient group. Clinical data and samples of PT-DLBCL patients treated at Helsinki, Tampere and Turku University Hospitals were collected, and in addition, Danish lymphoma registry was searched for PT-DLBCL patients. It was observed that PT-DLBCL patients with high international prognostic index (IPI) clearly benefitted from the addition of R to the treatment and that the treatment of contralateral testis associated with better survival among all PT-DLBCL patients. The present study demonstrates non-GCB phenotype in PT-DLBCL was associated with inferior survival. PT-DLBCL patients treated with iv CNS-directed treatment had significantly better survival than other patients. The present study identified absolute lymphocyte count (ALC) as a potential risk factor in PT-DLBCL. Non-lymphopenic PT-DLBCL patients receiving R as a part of their chemotherapy were found to have better survival in comparison to the patients not receiving R, whereas among lymphopenic patients, the difference in the outcome between the patients receiving R and not receiving R as part of their chemotherapy was not observed. Likewise, non-lymphopenic patients benefitted of iv CNS-directed therapy, whereas among lymphopenic patients no clear survival benefit was observed.
Original languageEnglish
Supervisors/Advisors
  • Leppä, Sirpa, Supervisor
  • Mäkitie, Antti, Supervisor
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-6375-2
Electronic ISBNs978-951-51-6376-9
Publication statusPublished - 2020
MoE publication typeG5 Doctoral dissertation (article)

Bibliographical note

M1 - 86 s. + liitteet

Fields of Science

  • 3122 Cancers

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