Prognostic factors for survival in patiens with chronic lymphocytic leukemia

Wijaya, Ferry (2012): Prognostic factors for survival in patiens with chronic lymphocytic leukemia: comparison of low risk and hiegh risk for progression binet stage A patients according to prospective risk stratification. Dissertation, LMU München: Medizinische Fakultät

Abstract

The purpose of this study is to analyse the quality of the prognostic factors to prognose the survival time and progression for patients with chronic lymphocytic leukemia (CLL) in early stage. In CLL-1-Protocol of the German CLL Study Group (GCLLSG) 877 patients with CLL in Binet stage A were included. These patients were assessed in terms of their progression risk using clinical and biological prognostic factors: bone marrow histology (infiltration type), lymphocyte doubling time (LDT), serum thymidine kinase, and serum-ß2-microglobulin. The patients with high progression risk would after randomization either receive treatment with fludarabine or only be observed, whereas the patients without high progression risk would be observed. In this study 630 patients without any treatment with fludarabine were analysed, 95 patients (15.1%) with high progression risk and 535 patients (84.9%) with low progression risk. The median observation time was 6 years. The following factors were analysed in this study: B symptoms, ECOG performance status, alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), gamma-glutamyltransferase (gamma-GT), cholinesterase (CHE), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), uric acid, serum creatinine, total bilirubin, hepatomegaly, splenomegaly, lymphadenopathy. In summary of the analysis in this study in terms of progression free survival, six parameters (lactate dehydrogenase, blood urea nitrogen, serum creatinine, splenomegaly, axillary lymphadenopathy, cervical lymphadenopathy) significantly predicted progression free survival. Patients with lactate dehydrogenase >= 250 U/L showed significant lower progression free survival ( 18.1 months vs. 60.6 months, p value<0.001). Patients with palpable splenomegaly showed significant lower progression free survival ( 20 months vs. 52.1 months, p value <0.01). Patients with pathologic palpable cervical lymphadenopathy showed significant lower progression free survival ( 19.9 months vs. 42.1 months, p value <0.01). Patients with pathologic palpable axillary lymphadenopathy showed significant lower progression free survival ( 21.4 months vs. 59.4 months, p value <0.01). Patients with blood urea nitrogen levels > 50 mg/dL showed significant lower progression free survival ( 18.7 months vs. 52.5 months, p value <0.032). Patients with serum creatinine levels >= 1.0 mg/dL for female and >= 1.2 mg/dL for male showed significant lower progression free survival ( 25.1 months vs. 59.4 months, p value <0.01). Only two parameters could predict significantly overall survival, namely blood urea nitrogen and serum creatinine. Elevated levels of blood urea nitrogen as well as elevated serum creatinine levels were associated with poorer prognosis. The other prognostic parameters (B-symptoms, ECOG performance status, alkaline phosphatase, serum glutamic oxalacetic transaminase, serum glutamate pyruvate transaminase, gamma-glutamyltransferase, cholinesterase, uric acid, total bilirubin, hepatomegaly, inguinal lymphadenopathy) could not predict progression free survival nor overall survival. All estimated parameters are easily to assess and belong to a routine work-up of CLL patients. Before suggesting a prognostic score of all these analyzed parameters, they have to be analyzed together with modern parameters like cytogenetic and molecular genetic parameter after a longer follow-up period of the study population using a multivariate Cox regression model to prove their significance for prognosis prediction. Nevertheless, all these significant parameters for progression-free survival and overall survival in the univariate analysis are worthwhile to test in a multivariate analysis.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 22. November 2012
• 1. Bericht­erstatter:in: Hallek, Michael