INTRODUCTION: High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), but serious infections are frequent. Recently published data suggested that high-dose dexamethasone might be equally effective as HDMP despite a lower cumulative dose. MATERIAL AND METHODS: We performed retrospective analysis of 60 patients with relapsed/refractory CLL (median age: 66 years; range: 37-86) treated with rituximab plus dexamethasone (R-dex) at a single tertiary center between September 2008 and October 2012. The schedule of R-dex consisted of rituximab 500 mg/m(2) i.v. day 1 (375 mg/m(2) in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13 repeated every 3 weeks for a maximum of 8 cycles. Unfavorable prognostic features were frequent (Rai stages III/IV in 67%, unmutated IgVH 82%, del 11q 43%, TP53 mutation/deletion 23%, bulky lymphadenopathy 58% of patients). RESULTS: Overall response (OR)/complete remission (CR) was achieved in 75/3%. At the median follow-up of 21 months, median progression-free survival (PFS) was 8 months, median time to next treatment 12.9 months and median overall survival 25.5 months. Refractoriness to fludarabine (p = 0.04) and age ≥ 65 years (p = 0.03) were significant predictors of shorter PFS. R-dex was successfully used for debulking before allogenic stem cell transplantation in 7 patients (12%). Serious (CTCAE grade III/IV) infections occurred in 27% of patients; 20% of patients developed steroid diabetes requiring temporary short-acting insulin. CONCLUSIONS: Our results show that R-dex is an active and well-tolerated regimen for patients with relapsed/refractory CLL; however, major infections remain frequent despite combined antimicrobial prophylaxis.

Department of Internal Medicine Hematology University Hospital and Charles University Prague Faculty of Medicine in Hradec Kralove Czech Republic

Zobrazit více v PubMed

Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010;28:1756–65. PubMed

Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–74. PubMed

Keating MJ, O'Brien S, Kontoyiannis D, et al. Results of first salvage therapy for patients refractory to a fludarabine regimen in chronic lymphocytic leukemia. Leuk Lymphoma. 2002;43:1755–62. PubMed

Tsimberidou AM, Keating MJ. Treatment of fludarabine-refractory chronic lymphocytic leukemia. Cancer. 2009;115:2824–36. PubMed

Pettitt AR. Glucocorticoid-based combination therapy for chronic lymphotic leukemia: new tricks for an old dog. Leuk Lymphoma. 2008;49:1843–5. PubMed

Thornton PD, Hamblin M, Treleaven JG, Matutes E, Lakhani AK, Catovsky D. High dose methyl prednisolone in refractory chronic lymphocytic leukaemia. Leuk Lymphoma. 1999;34:167–70. PubMed

Thornton PD, Matutes E, Bosanquet AG, et al. High dose methylprednisolone can induce remissions in CLL patients with p53 abnormalities. Ann Hematol. 2003;82:759–65. PubMed

Bowen DA, Call TG, Jenkins GD, et al. Methylprednisolone-rituximab is an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia including those with unfavorable cytogenetic features. Leuk Lymphoma. 2007;48:2412–7. PubMed

Castro JE, Sandoval-Sus JD, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia. 2008;22:2048–53. PubMed PMC

Dungarwalla M, Evans SO, Riley U, Catovsky D, Dearden CE, Matutes E. High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy. Haematologica. 2008;93:475–6. PubMed

Pettitt AR, Matutes E, Oscier D. Alemtuzumab in combination with high-dose methylprednisolone is a logical, feasible and highly active therapeutic regimen in chronic lymphocytic leukaemia patients with p53 defects. Leukemia. 2006;20:1441–5. PubMed

Pettitt AR, Jackson R, Carruthers S, et al. Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial. J Clin Oncol. 2012;30:1647–55. PubMed

Zenz T, Gribben JG, Hallek M, Dohner H, Keating MJ, Stilgenbauer S. Risk categories and refractory CLL in the era of chemoimmunotherapy. Blood. 2012;119:4101–7. PubMed PMC

Smolej L. The role of high-dose corticosteroids in the treatment of chronic lymphocytic leukemia. Expert Opin Investig Drugs. 2012;21:1009–17. PubMed

Quinn JP, Mohamedbhai S, Chipperfield K, Treacy M, D'Sa S, Nathwani AC. Efficacy of rituximab in combination with steroids in refractory chronic lymphocytic leukemia. Leuk Lymphoma. 2008;49:1995–8. PubMed

Rose AL, Smith BE, Maloney DG. Glucocorticoids and rituximab in vitro: synergistic direct antiproliferative and apoptotic effects. Blood. 2002;100:1765–73. PubMed

Smolej L, Doubek M, Panovska A, et al. Rituximab in combination with high-dose dexamethasone for the treatment of relapsed/refractory chronic lymphocytic leukemia. Leuk Res. 2012;36:1278–82. PubMed

Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–56. PubMed PMC

Pileckyté R, Jurgutis M, Valceckiene V, et al. Dose-dense high-dose methylprednisolone and rituximab in the treatment of relapsed or refractory high-risk chronic lymphocytic leukemia. Leuk Lymphoma. 2011;52:1055–65. PubMed

Wierda W, Kipps T, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28:1749–55. PubMed PMC

Castro JE, James DF, Sandoval-Sus JD, et al. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia. 2009;23:1779–89. PubMed PMC