Chemotherapy in non-Hodgkin’s lymphoma

De Wolf-Peeters, C., Mortelmans, L., and Ver-hoef, G. Prognostic value of positron emission tomography (PET) with fluorine-lSfluorode-oxyglucose ([ F]FDG) after first-line chemotherapy in non-Hodgkin s lymphoma is [ F]FDG-PETa valid alternative to conventional diagnostic methods ). Clin. Oncol., 19 414-419, 2001. 

Phihp T, Gugliemli C, Hagenbeek A, Somers R, et al. 1995. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin s lymphoma. NEJM. 333 1540-1545. 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

Bleomycin, in combination with cisplatin or etopo-side, is important as part of the potentially curative combination chemotherapy of advanced testicular carcinomas. Bleomycin is used in some standard regimens for the treatment of Hodgkin s and non-Hodgkin s lymphomas, and it is useful against squamous cell carcinomas of the head and neck, cervix, and skin. 

Tositumomab is another anti-CD20 monoclonal antibody and is complexed with iodine 131 (131I). Tositumomab is used in two-step therapy in patients with CD20-positive, follicular non-Hodgkin s lymphoma whose disease is refractory to rituximab and standard chemotherapy. Toxicities are similar to those for ibritumomab and include severe cytopenias such as thrombocytopenia and neutropenia. Tositumomab should not be administered to patients with greater than 25% bone marrow involvement. 

Combination chemotherapy is the treatment standard for patients with diffuse non-Hodgkin s lymphoma. The anthracycline-containing regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been considered the best treatment in terms of initial therapy. Recently, randomized phase III clinical studies have shown that the combination of CHOP with the anti-CD20 monoclonal antibody rituximab results in improved response rates, disease-free survival, and overall survival compared with CHOP chemotherapy alone. 

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. 

Quigley M, Brada M, Heron C, Horwich A. Severe lung toxicity with a weekly low dose chemotherapy regimen in patients with non-Hodgkin s lymphoma. Hematol Oncol 1988 6(4) 319-24. 

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. 

Acute febrile interstitial pneumonitis occurred within less than 48 hours after the second to fourth cycles of chemotherapy (doxorubicin, cyclophosphamide, bleomycin, methotrexate, plus methylprednisolone) in five patients with non-Hodgkin s lymphoma who were receiving prophylactic G-CSF n — 3) or GM-CSF (n = 2) (23). Lymphocytic alveolitis was confirmed in four of these patients and all three patients tested had an increased number of CD8+ T cells. Even though all the patients received high-dose methylprednisolone, two died as a result of diffuse and extensive interstitial pulmonary fibrosis, demonstrated at postmortem. Although both G-CSF and GM-CSF can cause acute pneumonitis in patients with cancers, it is still unknown to what extent hemopoietic growth factors are involved in this complication. 

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). 

The long-term prognosis for sperm counts after chemotherapy with and without radiation in 71 males treated for non-Hodgkin s lymphoma on the CHOP-Bleomycin combination has been studied (262). Pelvic radiotherapy and cumulative cyclophosphamide dosages of greater than 9.5 g/m are associated independently and in combination with a greater risk of permanent sterility. 

Pryzant RM, Meistrich ML, Wilson G, Brown B, McLaughlin P. Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-Hodgkin s lymphomas. J Clin Oncol 1993 ll(2) 239-47. 

Severe viral infections/reactivation that have been reported in patients given ritnximab have inclnded fnl-minant hepatitis B (18), parvovims-indnced red cell aplasia (15), and fatal Varicella zoster infection (19). There was a high incidence of reactivation of cytomegalovirus and V. zoster virus when rituximab was combined with high-dose chemotherapy in high-risk patients with non-Hodgkin s lymphoma (20). 

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