Lymphoma indolent

B. Indications and use Rituxan is the first FDA-approved monoclonal antibody for the treatment of cancer. Several clinical trials have demonstrated efficacy of this chimeric antibody against NHL. Rituxan is indicated for the treatment of patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin s lymphoma (indolent lymphoma). 

BCL-2 Codes for a protein that blocks apoptosis Indolent B-cell lymphomas... 

Delineate the clinical course of follicular indolent and diffuse aggressive non-Hodgkin s lymphoma and the implications for disease classification schemes and treatment goals. 

McLaughlin P, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma Half of patients respond to a four dose treatment program. J Clin Oncol 1998 16 2825-2833. 

Systems for classifying NHLs continue to evolve. Lymphomas can be classified by degree of aggressiveness. Slow-growing or indolent lympho-... 

Follicular lymphomas occur in older adults with a majority having advanced disease at diagnosis. The clinical course is generally indolent, with median survival of 8 to 10 years. The natural history of follicular lymphoma is unpredictable with spontaneous regression of objective disease seen in 20% to 30% of patients. 

Management of stages III and IV indolent lymphoma is controversial because standard approaches are not curative. Time to relapse is only 18 to 36 months. After relapse, response can be reinduced however, response rates and durations decrease with each retreatment. 

Hainsworth, J.D. et al., Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin s lymphoma, J. Clin. Oncol., 20,426, 2002. 

Bonner, J.A. et al., Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck a phase III study of high dose radiation therapy with or without cetuximab, Proc. Am. Soc. Clin. Oncol., 22, 489S, Abstr. 5507, 2004. McLaughlin, R et al., Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma half of patients respond to a four-dose treatment program, /. Clin. Oncol., 16, 2825-2833, 1998. 

Vinblastine and vincristine differ only in the substituent on the nitrogen atom of the indol fragment of the molecule, and are used in combination with other chemotherapeutic agents. They are mainly used for leukoses, myelomas, sarcomas, cancer of various organs, and for lymphomas. 

Schbder et al. recently showed that [ F]-FDG uptake is lower in indolent than in aggressive NHL [49]. A SUV >10 resulted in a higher likelihood for aggressive disease and excluded indolent lymphomas with a sensitivity of 81%. But nevertheless differentiation between aggressive and indolent lymphomas depending on the SUV leaves around 45% of the patients in a gray area. 

The best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

The CD52 antigen, a 21- to 28-kDa glycopeptide, is expressed at high density on the surface of B- and T-l5miphocytes, macrophages, and monocytes, but not hematopoietic stem cells (33). It is also expressed on all CLL cells and indolent B-cell lymphoma cells. The entire structure of the CD52 molecule has been determined. However, its function still remains to be revealed. 

Davies AJ, Rohatiner AZ, Howell S, Britton KE, et al. 2004. Tositumomab and Iodine 1131 tositu-momab for recurrent indolent and transformed B cell non-Hodgkin s lymphoma. J Clin Oncol. 22 1469-1479. 

Leahy MF, Seymour JF, Hicks RJ, Turner JH. 2006. Multicenter phase II clinical study of Iodine-13 1-Rituximab radiotherapy in relapsed or refractory indolent non-Hodgkin s lymphoma. J Clin Oncol. 24 4418-4425. 

The nodular follicular lymphomas are low-grade, indolent tumors that tend to present in an advanced stage and are usually confined to lymph nodes, bone marrow, and spleen. This form of non-Hodgkin s lymphomas, when presenting at an advanced stage, is considered incurable, and treatment is generally palliative. To date, there is no evidence that immediate treatment with combination chemotherapy offers clinical benefit over close observation and "watchful waiting" with initiation of chemotherapy at the time of disease symptoms. 

Mantle Cell Lymphoma (MCL). Although MCL is considered an indolent lymphoma, the median survival is less than for the other indolent tumors. The disease is primarily nodal however, the peripheral blood is involved in about 25% of cases. The benign counterpart is unknown (S31). 

Follicular Lymphoma (FL). These tumors are indolent, primarily nodal, lymphomas and are composed of a mixture of centrocytes and centro-blasts. These lymphomas are graded based on the number of centroblasts, which are the proliferating cells. 

Vinblastine is a highly effective anticancer agent currently used clinically against leukemia, Hodgkin s lymphoma, and other cancers. (113, 114). Vinblastine is derived from dimerization of vindoline and another terpenoid indole alkaloid, catharanthine. 

Sheppard RD, Samant SA, Rosenberg M, Silver LM, Cole MD. Transgenic N-myc mouse model for indolent B cell lymphoma Tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors. Oncogene 1998 17 2073-85. 

In a phase II study, 17 patients with progressive indolent non-Hodgkin s lymphoma, previously treated with chemotherapy, received bryostatin 1 (5). Phlebitis was initially due to the 60% ethanol formulation used for administration, and the subsequent use of another formulation (60% polyethylene glycol, 30% ethanol, 10% Tween 80) reduced the incidence. In one patient, bryostatin 1 was withdrawn because of grade 2 thrombo-cjdopenia. The dose-Umiting adverse effect was myalgia, which occurred in eight patients. 

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