Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease.

PURPOSE: The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). EXPERIMENTAL DESIGN: Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation. RESULTS: All patients were assessable for toxicity, and 39 of 42 (93%) patients were assessable for response. Six of 29 (21%) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/microl to 576/microl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37% of the patients. CONCLUSIONS: The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.

Marginal zone lymphomas: factors that affect the final outcome.

BACKGROUND: A retrospective review and analysis of 275 patients with marginal zone lymphoma (MZL) was performed to determine prognostic factors. An effort was also made to establish a specific prognostic score for patients with extranodal MZL. METHODS: Patients were divided into 3 groups according to the type of MZL: extranodal, nodal, and splenic. Factors analyzed included age; gender; presence of B symptoms; Zubrod performance score; clinical stage; serum ß(2)-microglobulin, lactate dehydrogenase, albumin, and hemoglobin levels; and presence of autoimmune disorder. RESULTS: The 5-year overall survival rates of patients with extranodal, nodal, and splenic MZL were 87%, 89%, and 93%, respectively (P = .95). On multivariate analysis, splenic MZL patients had the best prognosis (hazard ratio, 0.18; P = .018). An elevated serum ß(2)-microglobulin level (P = .010), B symptoms (P = .021), and male gender (P = .036) were found to be correlated with decreased recurrence-free survival (RFS) on multivariate analysis. Using these 3 variables, a 3-tier prognostic scoring system was created for patients with extranodal MZL: low-risk with no adverse factors, intermediate-risk with 1 adverse factor, and high-risk with ≥ 2 adverse factors. The 5-year RFS rates for the low-risk, intermediate-risk, and high-risk groups were 80%, 71%, and 44%, respectively (P = .01). CONCLUSIONS: Patients with extranodal and nodal MZL have a similar prognosis, whereas patients with splenic MZL have a better prognosis despite the increased prevalence of negative prognostic indicators. With the use of 3 readily available factors, a prognostic scoring system was identified for patients with extranodal MZL.

Clinical presentation and treatment of secondary orbital lymphoma.

PURPOSE: To describe the clinical features and histologic classification of orbital lymphoma secondary to systemic non-Hodgkin lymphoma, to evaluate the efficacy of various treatment modalities for controlling the orbital component of disease, and to analyze vision-related outcomes. METHODS: In this retrospective case series, the clinical records of patients diagnosed with orbital lymphoma who were treated between January 1999 and May 2001 at the University of Texas M.D. Anderson Cancer Center were reviewed. Demographic data, histologic classification of lymphoma, immunophenotype, stage of disease, treatment outcomes, vision-related outcomes, and duration of follow-up after the diagnosis of orbital lymphoma were recorded in each case. RESULTS: At the time of diagnosis, all 15 patients identified either had a previous history of non-Hodgkin lymphoma or had simultaneous involvement of lymph node or other sites. Ten patients (67%) had intermediate-grade or high-grade lymphoma. All 15 patients had a B-cell phenotype. Systemic chemotherapy or immunotherapy was the initial treatment modality in 13 patients; the other 2 patients were treated with radiation as the initial mode of therapy. Eleven patients (73%) achieved complete regression of the orbital tumor; one patient had partial regression of the orbital lymphoma. Loss of vision secondary to compressive optic neuropathy was seen in 5 patients (33%); in 3 of these patients, the orbital lymphoma was diagnosed early and treatment was successful in reversing the loss of vision. One patient had irreversible vision loss secondary to compressive optic neuropathy; in this case, therapy had not been initiated until several months after onset of symptoms. Another patient died of lymphoma before the orbital disease could have responded to therapy. CONCLUSIONS: Because of often widespread systemic involvement and a usually more aggressive histologic classification than primary orbital lymphomas, secondary orbital lymphomas warrant treatment with systemic chemotherapy or systemic immunotherapy. In some cases, combining such systemic therapy with local radiation treatment is beneficial. Loss of vision as the result of compressive optic neuropathy in this setting can be reversed if systemic therapy is initiated soon after the onset of progressive signs and symptoms of orbital disease.