Kronik Lenfositik Lösemili Hastaların Prognostik Özellikleri ve Tedaviye Yanıtlarının Retrospektif Olarak Değerlendirilmesi

Abstract

Chronic lymphocytic leukemia (CLL) is a disease with a wide range of clinic spectrum and outcome, and it is seen frequently in elderly population. It is important to determine the prognostic factors that affect the survival, and based on these prognostic factors we can detect high-risk patients. In recent years new treatment modalities improve the survival in patients with CLL. But there are few studies about prognosis and treatment of CLL in our country. In our study, we aimed to determine the prognostic factors and their effect on survival; to investigate the response of different treatment modalities and their impact on survival in CLL. Between January 2000 and June 2013, we analyzed the 245 patients diagnosed as CLL according to criteria of International Workshop on CLL (IWCLL). Clinical characteristics of patients, the pattern of bone marrow involvement, serum lactat dehydrogenase-LDH and ß2microglobulin levels, the findings of flow cytometry and flourescence in situ hybridization (FISH) (del17p, del11q), different treatment regimens, the response to treatment regimens acoording to IWCLL 2008 criteria, treatment-related and disease-related complications were analyzed. Based on prognostic factors we performed treatment free survival (TFS) and overall survival (OS) analysis. In addition to these we also analyzed response rates to treatment protocol, time to next treatment (TTNT1 and TTNT2) and OS after the treatment. We evaluated 245 patients whose median age was 62, male/female ratio was 1,6. The percentage of Rai stage III/IV was 21,7%. As a result; the presence of B symptoms, Rai stage II and more, Binet stage B and C disease, diffuse infiltration of bone marrow by lymphocytes, number of lymphadenopathy region 3 and more, eleveted LDH and ß2microglobulin level and CD (cluster of differantiation) 38 level above the 20%; reduce both TFS and OS (p<0,05) and indicate poor prognosis. Additionaly advanced age (age over 65), poor performance status (performans score 2 and more) and presence of del17p shorten the OS (p<0,05) and indicate poor prognosis, but they had no statistically significant influence on TFS. In mutivariate analyzis; we detected that advanced age independently associated with short OS, and high Rai stage independently associated with short TFS (p<0,05 for both). As initial treatment, highest ORR being 93,5% was obtained with fludarabine-cyclophosphamiderituximab (FCR), but no statistically significant difference was detected between treatment regimens. After FCR regimen none of the responders required second therapy. With FCR TTNT1=88,13 months (equal to OS); with fludarabinecyclophosphamide (FC) TTNT1= 45,7 months; with fludarabine TTNT1=37,7 months; with chlorambucil TTNT1=35 months were detected. There was a statistically significant difference between treatmen regimens acoording to TTNT1 (p=0,011) but no difference was detected according to OS (p=0,096). Grade 3-4 neutropenia was mostly seen with FCR as 71,4%, and major infections (pneumonia, sepsis, febrile neutropenia) were mostly (42,3%) seen with cyclophosphamide-vincristine-(adriamisin)-prednisolone (COP-CHOP) regimen. Number of relapsrefractory patients was insufficent and there were lots of different treatment protocols; so we couldn?t detect a statistically significant difference on survival and response rates between treatment regimens in second step. As a result; it is essential to determine poor prognostic factors to identify high-risk patients at the time of diagnosis and before treatment planning in CLL. We can obtain an increased response rate and improved treatment free survival with using FCR regimen as an initial treatment with an antimicrobial prophylaxis, in patients who have good performance status.