Kategorie: Maligní lymfomy a leukémie
Téma: Chronic lymphocytic leukemia and related disorders - Clinical (Poster)
Číslo abstraktu: P877
Autoři: prof. MUDr. Michael Doubek, Ph.D.; MUDr. Josef Srovnal, Ph.D.; Mgr. Karla Plevová, Ph.D.; MUDr. Jakub Trizuljak; MUDr. Yvona Brychtová, Ph.D.; MUDr. Lukáš Semerád; MUDr. Eva Létalová; Mgr. Andrea Benedíková; prof. MUDr. Jiří Mayer, CSc.; doc. MUDr. Marián Hajdúch, Ph.D.; prof. RNDr. Šárka Pospíšilová, Ph.D.
Background: Merkel Cell polyomavirus (MCPyV), a ubiquitous DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukaemia (CLL). Previous studies have reported conflicting results on the frequency and potential pathogenetic role of MCPyV in CLL. Moreover, the prognostic significance of MCPyV is unknown in CLL.
Aims: The aim of this study was to evaluate the association of MCPyV with CLL and to investigate the occurrence of MCPyV infection in relation to the course of CLL.
Methods: DNA CLL samples consecutively obtained from CLL patients (n=119) before treatment was tested for MCPyV using both quantitative real-time polymerase chain reaction analysis and next-generation sequencing. Furthermore, 21 patients were tested repeatedly after CLL therapy. Therefore, 140 samples were tested in total. Only samples being positive by both methods were considered to really be positive for MCPyV. The MCPyV have been compared with classical and biological prognostic CLL factors.
Results: We found that 13/119 CLL cases (11%) were positive for MCPyV. Between the groups of MCPyV-positive and -negative patients, there was no significant difference in the sex (5 positive females from 49; 8 positive males from 70); age (median age 60.5 years for positive and 60 years for negative patients); cytogenetics (unfavorable cytogenetics (del 17p or 11q) in 38% of positive patients and 24% of negative patients); presence of p53 defect (23% of positive patients vs. 20% of negative patients); IGHV mutational status (unmutated in 69% of positive patients and 76% of negative patients). Ad baseline, advanced Rai stage (III and IV) was found more frequently in MCPyV negative patients (15% vs. 41%; P=0.04). Therapy (FCR regimen or alemtuzumab) was also initiated more frequently in the negative group (46% vs. 68%; P=NS). There was no difference in overall response rate (86% in positive patients vs. 80% in negative patients), median progression-free survival (20 months in MCPyV negative vs. 24 months in MCPyV positive patients), and overall survival (not reached) between both groups. One CLL patient positive for MCPyV also developed Merkel cell carcinoma. Interestingly, in six initially MCPyV positive patients repeatedly tested, the virus was undetectable after treatment in four of them. We did not observe any new positivity after treatment in initially MCPyV negative patients.
Summary/Conclusion: This study provides the first analysis of the prognostic role of MCPyV in CLL. The occurrence with MCPyV seems to be a relatively rare event during the natural history of CLL. MCPyV is also unlikely to influence the outcome of CLL patients and MCPyV positivity may often disappear after CLL therapy.
Supported in part by Research Grants MSMT CR CZ.1.05/1.1.00/02.0068 (CEITEC), MSMT CR CZ.1.07/2.3.00/20.0045 (SuPReMMe), IGA NT13493/2012, VaVpI CZ.1.05/2.1.00/01.0030; by the European Commission under the Health Theme of the 7th Framework Programme for Research and Technological Development GA 306242; and by the Czech Leukemia Study Group – for Life.
Keywords: Chronic lymphocytic leukemia, Prognostic factor
Datum přednesení příspěvku: 14. 6. 2014