Follicular large cell lymphoma

Rodriguez J, McLaughlin R Hagenmeister FB, et al. Follicular large cell lymphoma an aggressive lymphoma that often presents with favorable prognostic features. Blood 1999 93 2202-2207. 

MM = multiple myeloma ATL = adult T-cell leukemia ALL = acute lymphoblastic leukemia CLL = chronic lymphocytic leukemia FCC = follicular center cell lymphoma DLC = diffuse large cell lymphoma TRB = T-cell rich B-cell lymphoma ALCL = anaplastic large cell lymphoma MALT = mucosa-associated lymphoid tissue-type lymphoma LC = lung cancer CMM = cutaneous malignant melanoma TCC = transitional cell carcinoma CSCC = cutaneous squamous cell carcinoma. 

CLL/SLL, Chronic lymphocytic leukemia/small lymphocytic lymphoma MCL, mantle cell lymphoma FL, follicular lymphoma MZL/MALT, marginal zone lymphoma/mucosa-associated lymphoid tisuse lymphoma SMZL, splenic marginal zone lymphoma HCL, hairy cell leukemia DLCL, diffuse large-cell lymphoma PCM, plasma cell myeloma BCL-1, cyclin D1 FDC MW, Follicular dendritic cell meshworks CK, cytokeratin LELs, lymphoepitheilal lesions. 

A large multicenter pivotal phase II study was performed to evaluate the efficacy of rituximab in the treatment of relapsed low-grade or follicular CD20(+) B-cell NHL (171). A total of 166 patients with small lymphocytic (n= 33), follicular small cleaved (n = 67), follicular mixed (n= 53), follicular large-cell (n = 10), or low-grade variant (n = 3) NHL were enrolled at 31 centers. Patients with bulky disease (>10 cm), pleural or peritoneal involvement, CNS lymphoma, AIDS-related lymphoma, CLL or leukemic component (more than 5,000 lymphocytes/pl) were excluded. Rituximab was again administered intravenously at 375 mg/m2 weekly for four doses. The overall response rate, which was the primary study end point, was... 

Interleukin-3 caused a transient rise in circulating atjrpical B lymphocytes, with enlargement of the spleen and lymph nodes in two patients with large-cell lymphoma and the development of a clonally-related transient plasmocytosis in one patient with relapsing follicular non-Hodgkin s lymphoma (SED-13,1109) (10,16). 

NHL has lead to several international projects to develop prognostic models in the most common types of NHLs—diffuse large cell lymphomas and follicular lymphomas. The International Non-Hodgkin s Lymphoma Prognostic Lactors Project was based on more than 2,000 patients with diffuse aggressive lymphomas treated with... 

Martinka M, Gomeau T, Foyle A, et al. Prognostic significance of t(14 18) and bcl-2 gene expression in follicular small cleaved cell lymphoma and diffuse large cell lymphoma. Clin Invest Med Clin Experiment. 1997 20(6) 364-370. 

A major breakthrough in the treatment of lymphoid malignancies was the discovery of monoclonal antibody activity, especially that of rituximab. Rituximab was the first monoclonal antibody approved by the U.S., FDA for the treatment of relapsed follicular lymphoma (1), and it has now been extensively used for the treatment of various lymphoid neoplasm which express CD20 antigen. Its efficacy has been also demonstrated against diffuse large B-cell lymphoma when administered as a combination regimen such as rituximab plus CHOP (R-CHOP) chemotherapy (2). 

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). 

K9. King, B. E., Chen, C., Locker, J., Kant, J., Okuyama, K., Falini, B., and Swerdlow, S. H., Immunophenotypic and genotypic markers of follicular center cell neoplasia in diffuse large B-cell lymphomas. Mod. Pathol. 13, 1219-1231 (2000). 

Skinnider, B. E, Horsman, D. E., Dupuis, B., and Gascoyne, R. D., Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma Correlation with 3q27 and 18q21 chromosomal abnormalities. Hum. Pathol. 30, 803-808 (1999). 

ALL, acute lymphocytic leukemia BL, Burkitt lymphoma B-CLL, B-cell chronic lymphocytic leukemia B-LBL, B-cell lymphoblastic lymphoma cHL, classic Hodgkin s lymphoma DLBCL, diffuse large B-cell lymphoma FL, follicular lymphoma LPHL, lymphocyte-predominant Hodgkin s lymphoma MCL, mantle cell lymphoma MZL, marginal zone B-cell lymphoma. 

The same t(14 18)(q32 q21) translocation described in the follicular lymphomas has been also identified in 15-35% of diffuse large B-cell lymphomas, a part of which seems to be transformed from the follicular lymphoma after the accumulation of other genetic abnormalities, in these cases the presence of the t(14 18) translocation indicates a poor prognosis. The overexpression of bd-2 is also found in many other lymphoid, myeloid and solid neoplasms. It is important to mention that the expression or the overexpression of bd-2 is not equivalent to the presence of the t(14 18) translocation-specific follicular lymphoma as it is expressed in many normal cells and in different tumors. The bd-2 is normally expressed in breast epithelium and many non-neoplastic lymphocytes including the small lymphocytes of mantle and marginal zones as well as thymus and many T-cell populations. Furthermore, bd-2 is frequently expressed in many soft tissue tumors such as solitary fibrous tumor, synovial sarcoma and rhabdomyosarcoma in addition to breast carcinoma and many lymphoma types as CLL and marginal cell lymphoma. 

The t(14 18) translocation in follicular and diffuse large B-cell lymphoma can be detected by PCR-based molecular methods using consensus primers to both bd-2 and JH regions. The PCR-based method allows the use of smaller amounts of DNA to detect this translocation, even low molecular DNA extracted from formalin-fixed paraffin-embedded tissue, bone marrow or fine needle aspiration. This method is efficient for the primary diagnosis of follicular lymphoma or to detect minimal residual tumor cells that are below the limit of detection using conventional diagnostic methods espedally after chemotherapy or bone marrow transplantation. 

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