Dose-dense high-dose methylprednisolone and rituximab in the treatment of relapsed or refractory high-risk chronic lymphocytic leukemia

Abstract

This study evaluated the efficacy and safety of dose-dense high-dose methylprednisolone (HDMP) plus rituximab (Rtx) in patients with high-risk CLL. Twenty-nine patients with relapsed or progressive CLL with adverse cytogenetics (17p deletion, TP53 mutation, 11q deletion, and/or trisomy 12) and/or progression within 12 months of fludarabine treatment were included. HDMP (1 g/m²) was administered daily for 5 days of each treatment course. Rtx was administered on days 1 (375 mg/m²) and 5 (500 mg/m²) of the first treatment course, on days 1 (500 mg/m²) and 5 (500 mg/m²) of the second course, and on day 1 (500 mg/m²) of courses 3–6. The cycles were repeated every 21 days. The overall response rate (ORR) was 62%, and 28% of patients had stable disease. In 13 patients with 17p deletion/TP53 mutation, ORR was 69%. After 22 months, the median progression-free and overall survivals were 12 and 31 months, respectively. The most frequent toxicity was hyperglycemia, and three deaths occurred in the study. Dose-dense treatment with HDMP and Rtx is an effective therapy with a favorable safety profile in patients with high-risk CLL, including those with 17p deletion/TP53 mutation.

Keywords:

• Chronic lymphocytic leukemia
• relapsed/refractory
• high-risk cytogenetics
• high-dose methylprednisolone
• rituximab
• TP53 mutation

Acknowledgements

We would like to thank Ugnius Mickys for pathology reports, and Reda Matuzeviciene and Ausra Janiulioniene for flow cytometry analysis. This study was supported by the European Economic Area (Iceland, Liechtenstein and Norway) and Norwegian Financial Mechanism grant No. 2004-LT0040-IP-1EEE.

Potential conflict of interest:

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