Disease-specific complications of chronic lymphocytic leukemia in binet stage a patients

Kwag, Doo Young (2012): Disease-specific complications of chronic lymphocytic leukemia in binet stage a patients: analysis of immunodeficiency, autoimmune constellations and infections in the CLL1-protocol. Dissertation, LMU München: Medizinische Fakultät

Abstract

Disease-specific Complications of Chronic Lymphocytic Leukemia in Binet Stage A Patients: Analysis of Immunodeficiency, Autoimmune Constellations and Infections in the CLL1-Protocol. Summary Background Most patients in early stages of chronic lymphocytic leukemia (CLL) present no disease-related defects such as hypogammaglobulinemia, impaired cellular immunity or neutrophil function. Therefore, the standard therapy for patients in early stages is to date only observation without treatment with chemotherapeutic agents. Fludarabine is the best studied purine analogues as well as a very effective drug for the treatment of CLL. Therefore, the CLL-1 study was designed to examine whether an early therapy with fludarabine for patients in early stages could bring clinical benefits, mainly in terms of response and survival. In this study, the incidence of various complications was evaluated and analyzed, whether the therapy with fludarabine in patients in early stages caused more complications. Methods The patients were assessed in terms of their progression risk through bone marrow histology (infiltration type), lymphocyte doubling time (LDT), serum thymidine kinase level and the serum-ß2-microglobulin level. The combination of a non-nodular bone marrow infiltration type or a LDT <12 months and a serum thymidine kinase level >7 U/l or a serum-ß2-microglobulin >3.5 mg/l indicates a high progression risk. Patients with high progression risk would be randomized into the treatment arm or the “watch and wait” arm. Patients in the treatment arm (cohort I) received fludarabine i.v. (25 mg/m2/day 5 days long, cycle repeat on day 28, maximum 6 cycles), whereas patients in the “watch and wait” group (cohort II) were only being observed. The third group, consisting of patients with low progression risk according to the definition above (cohort III) was also only being observed. 98 patients were randomized into cohort I (also called HR-F) and 95 patients into cohort II (also called HR-WW). . 535 patients were observed in the cohort III Results The incidence of infections and serious infections was higher in cohort I than cohort II & III (41.5% vs. 30.4% and 30.9%, 6.1% vs. 2.5% and 2.4%), although serious infections were rarely observed. The incidence of infection showed no difference between patients in the observation arms, regardless of the risk of progression (cohort II: 30.4%, Cohort III: 30.9%). The most common spectra were viral (39.8%) and bacterial (36.1%) infections, fungal infections were rare (1.5%). Respiratory tract and soft tissue were the most common sites of infection. In the analysis of risk factors for infection, the serum creatinine can be regarded as the best risk factor in our study. In addition, alkaline phosphatase, IgA, IgG, IgM, splenomegaly, low LDH, and low platelet count can be regarded as a risk factor for infection. Our data show a trend for the hypothesis that the risk of infection is higher in patients treated with fludarabine. The overall incidence of AIHA and AITP in all study arms was evaluated as follows; AIHA Cohort I: 6 patients (6.8%), cohort II: 4 patients (4.8%), cohort III: 9 patients (2.0%), AITP Cohort I: 19 patients (21.8%), cohort II: 3 patients (3.6%), cohort III: 15 patients (3.1%). Through this study, we observed that patients who received fludarabine therapy (cohort I), had a higher incidence of AIHA and AITP than in the other study arms. Conclusion This study shows a trend for the hypothesis that the risk of infections in patients treated with fludarabine is higher. In addition, the serum creatinine in our study is considered to be the best risk factor for infection. The analysis of the incidence of AIHA and AITP also shows that the risk of autoimmune complications is increased with fludarabine therapy.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Chronic Lymphocytic Leukemia(CLL),Infections, Impaired Immunity, Hypogammaglobuliemia, AIHA, AITP, Prognostic Factors of Infections.
• 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: 19. Juli 2012
• 1. Bericht­erstatter:in: Hallek, Michael