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Combination of rituximab and high-dose chlorambucil in therapy of small lymphocyte lymphoma / chronic lymphocytic leukemia

Introduction: Chronic lymphocytic leukemia / small lymphocyte lymphoma (CLL) is the most common leukemia among adult Caucasians. It is typically a disease of the elderly, with a median age of onset of 69 years. Clinical course of the disease is variable and the prognosis depends on the clinical stage at the time of diagnosis and other established prognostic factors. Despite the intensive promotion of fludarabin-based protocols as the fundamental treatment of CLL, high dose chlorambucil remains the most efficient monochemotherapy for these patients. Low toxicity, short treatment duration and favorable cost make this therapy a convenient platform for addition of non-toxic targeted drugs, like rituximab. Rituximab is a monoclonal antibody aimed at the CD20-antigen on the surface of B-lymphocytes. Aim: Combination of rituximab and chlorambucil has been in routine clinical use for some time. The aim of this research is to assess its effectiveness. Patients and methods: Twenty- five patients treated at KBC-Zagreb were included in this study. Median age was 67 years. Patients had received high-dose chlorambucil (10-20mg, median 18mg) continuously and 700-800 mg of rituximab. Eight cycels were planned. Treatment was conducted with or without addition of glucocorticoids. In analysis, patients were divided into groups depending on Binet and Rai stages and total tumor mass score as well as other prognostic factors. Adverse events (AE) were evaluated. Assessed outcomes were response rates and survival. Results: Complete remission (CR) was achieved in 12 patients (48%), partial remission (PR) in 7 (28%), 2 patients were refractory to therapy (8%) and in 4 treatment is still ongoing. After median follow-up of 15 months of survivors, progression-free survival (PFS) is 72% and overall survival (OS) 92%. Patients with Binet stage C and Rai stages 3 and 4 have a statistically significant lower PFS than patients with favorable stages (26% vs, 86%, p = 0, 047). The effect of total tumor mass (TTM) score as well as other prognostic factors on PFS was not statistically significant (p > 0, 05). Likewise, correlation between assessed prognostic factors hasn’t been proven. Serious toxicity occurred in 7 patients, 6 of whom were ≥ 65 years. However, correlation between age and toxicity wasn’t statistically significant. The most common serious AE was leukopenia. Conclusion: Combination of rituximab and continuous high- dose chlorambucil is a very effective front- line treatment of CLL, leading to high overall response. Therapy does not cause unexpected toxicity and is well tolerated. To obtain more relevant results for comparison with larger studies, further follow-up and inclusion of new patients is needed.

chronic lymphocytic leukemia ; chlorambucil ; rituximab ; PFS

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