Chronic lymphocytic leukemia Rituximab

Chronic lymphocytic leukemia (CLL) patients who receive fludarabine-based combination chemotherapy and rituximab may have long-term disease-free survival. 

Jilani, L, O Brien, S., Manshuri, T, Thomas, D.A., Thomazy V.A., Imam, M., Naeem, S., Verstovsek, S., Kantarjian, H., Giles, R, Keating, M., and Albitar, M., Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia. Blood, 102, 3514-3520, 2003. 

Hainsworth, J.D., Litchy, S., Barton, J.H., Houston, G.A., Hermann, R.C., Bradof, J.E., and Greco, RA., Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma a phase II trial of the Minnie Pearl Gancer Research Network, /. Clin. Oncol., 21,1746-2751, 2003. 

Keating, M. and O Brien, S., High-dose rituximab therapy in chronic lymphocytic leukemia, Semin. Oncol., 27, 86-90, 2000. 

This chapter reviews our current understanding of the mechanism of action of monoclonal antibody (especially rituximab), as well as the role of Fey receptor and Fey receptor gene polymorphisms, and their impact on treatment outcomes in hematologic malignancies including follicular lymphoma (FL), diffuse large B-cell lymphoma (DL-BCL), Waldenstrom s macroglobulinemia (WM), and chronic lymphocytic leukemia (CLL). 

Kennedy AD, Beum PV, Solga MD et al. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. JImmunol 2004 172 3280-3288. 

Farag, SS, Flinn IW, Modali R et al. Fc gamma Rllla and Fc gamma Rlla polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia. B/ooii2004 103 1472-1474. 

S. Lerner, and M.J. Keating. 2001. Rituximab dose-escalation trial in chronic lymphocytic leukemia. /. Clin. Oncol. 19 2165-2170. 

Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999 94(7) 2217-24. 

Hegde UP, Wilson WH, White T, Cheson BD. Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia. Blood 2002 100(6) 2260-2. 

A 55-year-old man with chronic lymphocytic leukemia and rheumatoid arthritis took methotrexate for 4 years and developed a B cell non-Hodgkin s lymphoma in the shoulder and axillary lymph nodes he had Epstein-Barr viral antigens in the serum. After radiation and chemotherapy had failed, complete remission was achieved with a combination of rituximab and EPOCH (etoposide -I- prednisone -I- vincristine -I-cyclophosphamide + doxorubicin). 

Plosker GL, Figgitt DP. Rituximab a review of its use in non-Hodgkin s lymphoma and chronic lymphocytic leukemia. Drugs 2004 63 803-843. Anonymous. Iodine-131 tositumomab [Bexxar] for treatment of lymphoma. Med Lett 2003 45 86-87. 

Schulz H, Klein SK, Rehnald U, et al. Phase 2 smdy of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia. Blood 2002 100 3115-3120. 

Khouri IF, Lee MS, Saliba RM, et al. Non-myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia impact of rituximab on immunomodulation and survival. Exp Hematol 2004 32 28-35. 

Keating MJ et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. Journal of Clinical Oncology 2005 23 4079-4088. 

Infection risk In a study of consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia, alemtuzumab was associated with five deaths resulting from infections (viral, Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis jirovedi pnemnonia), which occurred up to 7 months after the last administration [bS "]. 

Chronic lymphocytic leukemia (CLL) is an accumulative disease of mature B lymphocytes. Rituximab, either alone or in combination with fludarabine, has proved to represent a highly effective form of therapy for this disease. In addition, Alemtuzumab (Campath anti-CD52) has also been shown to be very active in CLL, although it has significant immunosuppressive activity. More recently, a novel infusional schedule of the CDK inhibitor fiavopiridol has shown impressive activity in patients with refractory CLL. 

Infection risk Serious infections, including deaths, can occur during therapy with rituximab. Infectious events (predominantly bacterial and viral) occurred in 30-55% of patients with non-Hodgkin s lymphoma and in 30-50% of patients with chronic lymphocytic leukemia. In other therapeutic indications, the risk of infections seems to be less, but still increased compared with placebo [272=, 288", 289", 29Q, ... 

The safety of immunization with live viral vaccines after rituximab therapy has not been studied in patients with non-Hodgkin s lymphoma or chronic lymphocytic leukemia, and immunization with hve virus vaccines is not recommended. Immunization with other non-hve vaccines seems to be impaired following rituximab therapy [270", but immunization is not contraindicated. 

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