We have studied, as part of a group of international multicenter phase II clinical trials, the toxicity and effectiveness of CAMPATH1H administered intravenously three times a week in an outpatient setting to patients with recurrent or progressive low grade lymphoma. We report here on the toxicity and therapeutic results of the first seven patients treated before the study was closed prematurely because of unacceptable toxicity. Classical complete or partial responses of treatment were seen in three of seven patients. One complete response lasted 8.5 months and the other complete response is ongoing at 1 year. Responses occurred in nodal sites as well as in skin and peripheral blood. The first three or four antibody infusions in each patient was associated with grade 1 or 2 side-effects including rigor, fever, facial flushing, nausea, vomiting, hives, wheezes, hypotension, and/or diarrhea but these subsequently decreased or disappeared. The most significant toxicity was profound lymphopenia and associated infection, usually viral. Six of seven patients had culture or serologically documented infections and four patients had two or more such episodes. All infections responded to temporary discontinuation of antibody therapy and appropriate antiviral or antibiotic agents. We conclude that CAMPATH1H monoclonal antibody has therapeutic activity against low grade non-Hodgkin's lymphoma but that this activity is limited by marked lymphopenia and an unacceptably high frequency of serious infection at the dose and schedule used in this trial.

Patients with non-Hodgkin's lymphoma may develop retinal or choroidal lesions during the course of their disease. New immunosuppressive therapies currently used in reticuloendothelial malignancies have increased the incidence of opportunistic infections in this patient population. The differentiation of lymphomatous infiltration from opportunistic infection as a cause of chorioretinal infiltrates is critical, as the treatments are fundamentally different. We report a case of a patient with non-Hodgkin's lymphoma who developed a chorioretinal infiltrate that was initially thought to represent progressive disease. The patient received radiation treatment appropriate for intraocular lymphoma. The lesion progressed further and after reevaluation a diagnosis of cytomegalovirus retinitis was made and therapy initiated. Review of the literature for intraocular lymphoma and cytomegalovirus retinitis is provided and diagnostic strategies are described. We recommend analysis of intraocular fluid when there is difficulty in clinically differentiating intraocular lymphoma from opportunistic infection.

Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.

Because of evidence that failure to deliver full dose CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) may compromise the outcome of elderly patients with aggressive non-Hodgkin's lymphoma (NHL), we attempted to deliver full dose CHOP to these patients. The objective of this review was to assess the relative received dose intensity (ARRDI), toxicity and outcome of elderly patients treated with curative intent with CHOP at our centre. Charts were reviewed of all patients > or = 65 years with newly diagnosed aggressive NHL referred to the Toronto-Sunnybrook Regional Cancer Centre (TSRCC) for initial management from 1990-1995 before routine use of G-CSF. Sixty eligible patients were identified. 31 received CHOP +/- radiation (XRT), 9 other curative treatment and 20, palliative treatment. The mean ARRDI calculated on 29/31 patients receiving CHOP was .86; 41%=1.0, 24%=.90-.99, 14%=.75-.89 and 21%=<.75. During 141 cycles of CHOP. 17 (12%) episodes of febrile neutropenia (FN) occurred in 14 (45%) patients and other grade 3/4 toxicity occurred in <10% of patients. There were 3 (10%) toxic deaths. Sixteen (52%) patients required a total of 29 admissions to hospital for FN (59%) or other causes. Of the 31 patients, 16 (52%) achieved a complete remission (CR), 7 (23%) a partial remission-1 (PR-1), 2 (6%) a partial remission-2 (PR-2), 1 (3%) had no response (NR), 2 (6%) had progressive disease and 3 (10%) were not evaluable (NE). The median progression free survival (PFS) and overall survival (OS) were (16+) months and (24.5) months respectively. We found that physician biases resulted in the selection of; younger patients (median 71 vs. 80 years), patients with a better ECOG performance status (> or =2, 13% vs. 50%) and patients with less co-morbid illness (42% vs. 90%) for attempt at curative treatment with CHOP chemotherapy. Age was never the sole reason for offering palliative treatment. In conclusion, a subset of patients over the age of 65 with aggressive NHL, who have a good performance status and minimal co-morbid illness can tolerate full dose CHOP chemotherapy without G-CSF support. Future strategies should emphasize full dose treatment with curative intent with minimization of both hematologic and non-hematologic toxicity. Clinical studies are required to determine whether routine G-CSF support will reduce toxicity or improve outcome in this group of patients.