Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.

Infusional CHOP chemotherapy (CVAD) with or without chemosensitizers offers no advantage over standard CHOP therapy in the treatment of lymphoma: a Southwest Oncology Group Study.

PURPOSE: Two phase II studies were conducted to evaluate infusional cyclophosphamide, doxorubicin, vincristine, and dexamethasone chemotherapy, termed the CVAD regimen, alone (Southwest Oncology Group [SWOG] 9240) and with the chemosensitizers verapamil and quinine (SWOG 9125) to assess effects on response, survival, and toxicity in intermediate- and high-grade advanced-stage non-Hodgkin's lymphoma (NHL). The results were compared with the historic group of patients randomized to CHOP chemotherapy on Intergroup (INT) 0067 (SWOG 8516). PATIENTS AND METHODS: All patients had biopsy-proven intermediate- or high-grade NHL (lymphoblastic histology excluded), were ambulatory and previously untreated, and had bulky stage II, III, or IV disease. One hundred twelve patients were registered on SWOG 9240 and received cyclophosphamide 750 mg/m(2) by intravenous bolus day 1, doxorubicin 12.5 mg/m(2)/d and vincristine 0.5 mg/d delivered as a continuous 96-hour infusion on days 1 through 4, and dexamethasone 40 mg/d orally on days 1 through 4 (CVAD). Cycles were repeated every 21 days for eight cycles. One hundred patients on SWOG 9125 received the same chemotherapy and the chemosensitizers verapamil 240 mg bid and quinine 40 mg tid. Chemosensitizers were begun 24 hours before chemotherapy and continued for a total of 6 days. RESULTS: Eighty-one patients were eligible for each study. The complete response (CR) rates were 39% on SWOG 9125 and 31% on SWOG 9240. With a median follow-up of 5.8 years on SWOG 9125 and 4.5 years on SWOG 9240, the 2-year failure-free survival (FFS) rate was 42% on SWOG 9125 and 41% on SWOG 9240. Two-year overall survival (OS) rate was 64% on SWOG 9125 and 58% on SWOG 9240. These results are comparable to a 44% CR rate, a 2-year FFS of 46%, and 2-year OS of 63% observed in 225 patients treated with CHOP on INT 0067 (SWOG 8516). CONCLUSION: CVAD combination chemotherapy alone or with the chemosensitizers verapamil and quinine is not promising therapy with respect to improved response or OS in intermediate- and high-grade advanced-stage NHL.

Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809.

PURPOSE: S8809 is a randomized phase III trial determining whether intensive cytoreductive treatment, followed by interferon consolidation at the time of minimal residual disease, prolongs the progression-free survival (PFS) or overall survival (OS) of indolent lymphoma patients. PATIENTS AND METHODS: Five hundred seventy-one patients with previously untreated stage III or IV low-grade non-Hodgkin's lymphoma were registered. Patients received six to eight cycles of prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide/mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE[day 1]-MOPP[day 8]) chemotherapy or chemotherapy plus radiotherapy. Responding patients were randomized to observation alone or to interferon consolidation. Interferon alpha-2b 2 mU/m(2) was given subcutaneously three times weekly for 2 years. RESULTS: Two hundred sixty-eight eligible patients were randomized to interferon alpha consolidation (n = 144) or observation alone (n = 124). With a median follow-up time from randomization among patients still alive of 6.2 years, the median PFS time was 4.1 years for patients who received interferon consolidation therapy and 3.2 years for patients who were observed after ProMACE-MOPP induction (P =.25). The adjusted hazard ratio for relapse for observation to interferon was 0.83 (95% confidence interval [CI], 0.61 to 1.13). The median OS has not been reached in either group. At 5 years, OS is 78% for the interferon group and 77% for the observation group (P =.65). The adjusted hazard ratio for survival for observation to interferon is 1.11 (95% CI, 0.69 to 1. 79). CONCLUSION: Interferon alpha consolidation therapy after intensive treatment with anthracycline-containing combination chemotherapy and involved-field radiation therapy does not prolong the PFS or OS of patients with low-grade non-Hodgkin's lymphoma.

Daily subcutaneous ultra-low-dose interleukin 2 with daily low-dose interferon-alpha in patients with advanced renal cell carcinoma.

A limited institution Phase II pilot study was performed using a very low-dose combination of daily s.c. interleukin (IL)-2 with IFN-alpha-2b in patients with advanced renal cancer in an attempt to duplicate or increase the response documented with higher dose schedules without the attendant toxicity profile. We selected a dose of IL-2 with documented immunological activity and combined it with clinically active low-dose IFN. Between August 1994 and September 1996, 19 patients with metastatic renal cell carcinoma, who had been judged incapable of tolerating high-dose i.v. IL-2, were treated with IL-2 (1 million units/m2/day) and IFN (1 million units/day), administered s.c. daily. All treatments were administered on an outpatient basis. Virtually all patients had bulky tumor burden with multiple sites of involvement, including five patients with bone metastases. No major objective responses were observed; however, one patient experienced a minor response lasting 13 months, with an associated improvement in performance status. Median survival was 6 months, and 1-year survival was 16%. Toxicity was generally mild and consisted almost entirely of constitutional symptoms. No serious grade 3 or 4 toxicity was observed, although two patients withdrew from treatment due to treatment-related fatigue. On therapy, mild eosinophilia but no lymphocytosis was noted; in fact, peripheral lymphocyte counts decreased, only to rebound after treatment was discontinued. No toxic deaths occurred. Despite the reasonable tolerability of this daily low-dose s.c. regimen, we conclude that this regimen is an ineffective treatment in metastatic renal cell carcinoma patients who are incapable of tolerating high-dose i.v. IL-2.

Colosplenic fistula in a patient treated with interleukin-2 for malignant melanoma.

Interleukin-2 (IL-2) therapy often causes gastrointestinal side effects and at least 8 cases of bowel perforation have been reported. The patient reported here developed a colosplenic fistula, diagnosed by CT, with no neoplastic involvement of these organs. Awareness of these complications of IL-2 can help lead to earlier diagnosis.

Chemotherapy of intermediate-grade non-Hodgkin's lymphoma: is "more" or "less" better?

While it would seem obvious that dose intensity is an important determinant of treatment outcome in aggressive lymphomas, actually there are very few prospective data to support this hypothesis. Circumstantial evidence derived from retrospective analyses suggests that dose intensity is of clinical significance. However, based on available phase II and III data and the one prospective randomized trial to date that has specifically addressed this issue, it remains unclear what impact dose intensity has on treatment outcome.

Phase II trials of high-dose interleukin-2 and lymphokine-activated killer cells in advanced breast carcinoma and carcinoma of the lung, ovary, and pancreas and other tumors.

Treatment with interleukin-2 (IL-2) used alone or in combination with lymphokine-activated killer (LAK) cells is known to be an active therapy for patients with advanced renal cell carcinoma and melanoma. To further explore the activity of IL-2/LAK cell therapy in patients with advanced cancer of various primary sites, the Extramural IL-2/LAK Working Group (ILWG) initiated two phase II trials of high-dose IL-2/LAK therapy: one in patients with advanced breast carcinoma, and one in patients with advanced cancer arising in other sites. Patients with advanced renal cell carcinoma, melanoma, colorectal carcinoma, and lymphoma (Hodgkin's and B-cell non-Hodgkin's) were not eligible for the latter trial, but were treated on other ILWG trials that have been reported previously. Sixty-nine patients received high-dose IL-2 (600,000 IU/kg administered by a 15-min intravenous infusion every 8 h) on days 1-5 and days 11-15. Leukapheresis was performed for collection and ex vivo expansion of LAK cells on days 7-10, and the LAK cells were reinfused on days 11, 12, and 14. The studies were designed to determine whether treatment with IL-2/LAK resulted in at least a 40% response rate, a level of activity that was believed to be sufficient to justify the toxicity and cost of IL-2/LAK therapy. An adequate number of patients with carcinoma of the breast (N = 12), pancreas (N = 8), ovary (N = 7), and lung (non-small cell; N = 6) were accrued to assess response; most of these patients had prior chemotherapy that had failed.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study.

BACKGROUND: CHOP is a four-drug, first-generation combination chemotherapy regimen that has cured approximately 30% of all patients with advanced stages of intermediate- or high-grade non-Hodgkin's lymphoma in national cooperative group trials. Initial single-institution studies of third-generation regimens such as m-BACOD, ProMACE-CytaBOM, and MACOP-B suggested that 55%-60% of these patients might be cured. PATIENTS AND METHODS: In order to make a valid comparison between these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology Group initiated a randomized phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B. Endpoints of the study were response rate, time to treatment failure, overall survival, and severe or life-threatening toxicity. Received dose intensity calculations and subset analyses were also performed. RESULTS: 1138 patients were registered on this clinical trial. Each treatment arm contained between 218 and 233 eligible patients. Known prognostic factors were equally distributed. The initial results of this study were recently published. There were no significant differences in either the partial or complete response rates between treatment arms. Now after a median follow-up of 49 months and a maximum follow-up of 84 months, there is still no difference in time to treatment failure (p = 0.40) or overall survival (p = 0.68). No subset of patients was found to have significantly improved survival with the third-generation regimens. The received dose intensity data were comparable to previously published data for these regimens. Fatal toxicity was 1% for CHOP, 3% for ProMACE-CytaBOM, 5% for m-BACOD, and 6% for MACOP-B. CONCLUSION: Based on similar failure-free and overall survival with lower cost and lower severe toxicity, CHOP remains the standard chemotherapy for patients with advanced-stage, intermediate- or high-grade non-Hodgkin's lymphoma. New treatment strategies need to be developed to improve the prognosis of these patients.

Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma.

BACKGROUND: CHOP is a first-generation, combination-chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone that has cured approximately 30 percent of patients with advanced stages of intermediate-grade or high-grade non-Hodgkin's lymphoma in national cooperative-group trials. However, studies at single institutions have suggested that 55 to 65 percent of such patients might be cured by third-generation regimens such as ones consisting of low-dose methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD); prednisone, doxorubicin, cyclophosphamide, and etoposide, followed by cytarabine, bleomycin, vincristine, and methotrexate with leucovorin rescue (ProMACE-CytaBOM); and methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). METHODS: To make a valid comparison of these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology Group initiated a prospective, randomized phase III trial. The study end points were the response rate, time to treatment failure, overall survival, and incidence of severe or life-threatening toxicity. Dose intensity was calculated and analyzed. RESULTS: Of the 1138 patients registered for the trial, 899 were eligible. Each treatment group contained at least 218 patients. Known prognostic factors were equally distributed among the groups. There were no significant differences among the groups in the rates of partial and complete response. At three years, 44 percent of all patients were alive without disease; there were no significant differences between the groups (41 percent in the CHOP and MACOP-B groups and 46 percent in the m-BACOD and ProMACE-CytaBOM groups; P = 0.35). Overall survival at three years was 52 percent (50 percent in the ProMACE-CytaBOM and MACOP-B groups, 52 percent in the m-BACOD group, and 54 percent in the CHOP group; P = 0.90). There was no subgroup of patients in which survival was improved by a third-generation regimen. Fatal toxic reactions occurred in 1 percent of the CHOP group, 3 percent of the ProMACE-CytaBOM group, 5 percent of the m-BACOD group, and 6 percent of the MACOP-B group (P = 0.09). CONCLUSIONS: CHOP remains the best available treatment for patients with advanced-stage intermediate-grade or high-grade non-Hodgkin's lymphoma.

Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney. A Southwest Oncology Group study.

The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose.

Bleomycin in non-Hodgkin's lymphoma.

Bleomycin is a cell-cycle--specific chemotherapeutic agent, with several interesting properties, that lends itself to use in combination chemotherapeutic protocols, especially those for malignant lymphomas. In the following article, bleomycin's use as a single agent and subsequently in three generations of combination chemotherapeutic regimens is reviewed. Bleomycin's lack of myelosuppression and its tendency to concentrate in lymphoid tissue while maintaining tolerable toxicities has been the rationale for its incorporation into more aggressive treatment regimens.

A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma.

PURPOSE: Since 1985, multiple centers have demonstrated that interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells produce durable anticancer responses in patients with metastatic renal cell carcinoma. High-dose recombinant IL-2 (rIL-2) has been administered by intravenous bolus injection (Rosenberg SA, et al: N Engl J Med 313:1485-1492, 1985) and by continuous intravenous infusion (West WH, et al: N Engl J Med 316:898-905, 1987) combined with lymphokine-activated killer (LAK) cells, with both methods producing responses in patients with advanced renal cell carcinoma. The Extramural IL-2/LAK Working Group has conducted a randomized phase II trial of two intravenous high-dose rIL-2 regimens (bolus three times daily or 24-hour continuous infusion) to determine if either one manifests greater anticancer activity or a more acceptable toxicity profile. PATIENTS AND METHODS: Ninety-four patients with measurable advanced renal cell carcinoma were enrolled on this study: 46 to the bolus injection arm and 48 to the continuous infusion arm. On both arms, patients underwent a priming phase of rIL-2 administration, four daily lymphocytaphereses to harvest mononuclear cells that were placed in 3- to 4-day culture for generation of LAK cells, and an rIL-2/LAK coadministration phase. Patients were then observed monthly for evidence of response to this therapy and were offered up to two additional courses of treatment every 3 months if evidence of response was detected. RESULTS: Twenty percent of patients on the bolus injection arm experienced objective responses (three complete responses and six partial responses); 15% of patients on the continuous infusion arm responded (two complete responses and five partial responses). Complete responses were durable, persisting for 310+ to 700+ days. The incidence of severe life-threatening toxicities typical of high-dose rIL-2 therapy was similar in both arms (eg, patients with hypotension requiring pressors: bolus 71%, continuous 63%; oliguria less than or equal to 200 mL/8 hours: bolus 65%, continuous 71%). More episodes of fever, infection, and serum alkaline phosphatase elevation were associated with the continuous infusion arm, while more thrombocytopenia occurred on the bolus injection arm. Four patients (three bolus injection, one continuous infusion) died of respiratory and circulatory failure while under treatment. No clinical or laboratory parameter accompanying treatment on either arm was, by univariate or multivariate analysis, associated with an increased likelihood of response. CONCLUSIONS: Both methods of high-dose rIL-2/LAK cell administration produce nearly equivalent anticancer activity and toxicity in the treatment of renal cell carcinoma. The ability to predict responding patients based on patient or treatment characteristics is not possible.

Clinical trials of alpha-interferon in the treatment of non-Hodgkin's lymphoma.

Patients with non-Hodgkin's lymphomas are classified by the Working Formulation into low, intermediate, and high grade based on the aggressiveness of the lymphoma. Intermediate- and high-grade lymphomas are rapidly progressive, fatal diseases unless the patient achieves a complete remission after treatment with combination chemotherapy. Complete remissions have been reported in 40% to 80% of these patients, and 30% to 60% of these patients are actually cured. alpha-Interferon studies of relapsed patients have resulted in approximately a 15% objective response rate with only 2% complete remissions. Thus at this time alpha-interferon has no role in the treatment of these patients. Treatment of low-grade lymphomas with combination chemotherapy results in complete remission rates varying from 25% to 70%. However, these complete remissions are not durable and the patients essentially all relapse with a 22-month median duration of complete remission. In spite of these relapses, median survival for all patients exceeds 7 years. alpha-Interferon has shown beneficial clinical activity in the low-grade lymphomas. Overall response rates are approximately 46%, with 11% complete remission. There is some evidence to suggest that there is a useful dose-response curve, with the highest remission rates being seen at the highest alpha-interferon doses. The median duration of response is approximately 8 months. Combining alpha-interferon with standard chemotherapy has not resulted in an easily detectable improvement in response rate or duration. The role of alpha-interferon in prolonging remission duration for these low-grade lymphomas is being investigated by the Southwest Oncology Group. In summary, alpha-interferon has shown moderate activity when used to treat patients with low-grade non-Hodgkin's lymphomas.

Chemotherapy and combined modality treatment in Hodgkin's disease.

Several issues in the management of Hodgkin's disease remain to be resolved. These include 1) the most appropriate and effective first-line therapy for advanced disease, 2) the best approach to management of bulky mediastinal disease, 3) the management of uncommon presentations such as subdiaphragmatic disease, and 4) the best approach to salvage therapy for the patient with relapsed or refractory disease. Despite several years of clinical research and several significant advances in the treatment of this disease, the most effective treatment with the minimum amount of acute and delayed toxicity remains to be defined for several subsets of patients. This article reviews recent publications addressing these issues.

A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma.

Thirty-three patients with metastatic melanoma were treated in a phase II study with an intravenous continuous infusion (IVCI) of interleukin-2 (IL2) given with lymphokine-activated killer (LAK) cells. The dose of IL2 was the optimal priming dose for LAK-cell induction, followed by the maximally tolerated LAK-cell dose that could be given by an IVCI schedule as determined by a previous phase I trial. The CI schedule was chosen for evaluation because of a postulated reduction in toxicity with the possibility of administering a more prolonged IL2 infusion and because greater rebound lymphocytosis and LAK-cell generation had been reported using this dose and schedule. The 33 patients were similar in age, performance status, and sites of disease to those treated in previous IL2 trials. All patients were assessable for response and toxicity. One patient (3%) achieved a partial response of 10 months duration. There were no other clinically significant responses. Significant toxicity included hypotension requiring pressors (45%), dyspnea (36%), renal insufficiency (24%), hepatic dysfunction (66%), and cardiac arrhythmias (18%). These toxicities reversed with cessation of the infusion. There were four deaths during the first 30 days of treatment, three from infection (one related to central line, one related to LAK cells, one related to tumor), and one from tumor-related hemorrhage. Toxicity was unexpectedly high and at least comparable to that seen in previous studies using a high-dose IV bolus schedule of IL2. When comparing the IVCI schedule with high-dose bolus IL2 to LAK cells in nonrandomized but sequential studies in patients with advanced melanoma, it appears that CI IL2 is less efficacious.

A phase I study of high-dose interleukin-2 in combination with interferon-alpha 2b.

Our group and others have conducted phase II trials of high-dose interleukin-2 (IL-2) or IL-2 with the adoptive transfer of in vitro activated lymphocytes in patients with advanced malignancies. Although durable complete and partial responses were seen in patients with renal cell carcinoma and metastatic melanoma, overall response rates were low and toxicity was substantial. In preclinical models, the combination of IL-2 and interferon-alpha has synergistic antitumor activity. Based on these data, and our prior experience with high-dose IL-2 (Cetus), we conducted a trial to determine the maximum tolerated dose of IL-2 (0.4, 0.8, and 1.2 mg/m2) administered together with a fixed dose of interferon-alpha 2b (3 x 10(6) u/m2) intravenously every 8 h on days 1-5 and 15-19. Patients were monitored in the intensive care unit and given pressor support for hypotension as needed. Twenty-four patients were entered (6, 10, and 8 at each IL-2 dose, respectively; 14 renal cell carcinoma, 7 melanoma, 2 colon, and 1 hepatoma). The median age was 56 years, the male to female ratio was 19:5, and performance status was 0 or 1 (Eastern Cooperative Oncology Group) in all patients. Toxicity was similar at all dose levels, but the onset was earlier in the treatment course as the dose of IL-2 was escalated in successive cohorts; therefore, more doses were withheld at the higher dose levels. The major toxicities resulting in the interruption or stopping of treatment were hypotension requiring pressors, dyspnea, and neurotoxicity. Grade 1 or 2 fever, nausea and vomiting, fatigue, and cutaneous reactions were common at all dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen.

Forty-seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK)-cell therapy, using a hybrid IL-2 regimen. IL-2 was administered initially by intravenous bolus (10(5) U/kg [Cetus Corp, Emeryville, CA] every 8 hours for 3 days) during the priming phase, and subsequently by continuous infusion (3 x 10(6) U/m2 for 6 days); during this second treatment period, in vitro-generated LAK cells were administered. Despite selection of patients for good performance status (PS) (29, PS 0; 18, PS 1) prior nephrectomy (43 of the 47 patients), and low tumor burden, the response rate was low (two complete [CRs] and two partial responses [PRs], for an overall objective response rate of 9%). Toxicity was comparable to that experienced with the high-dose bolus regimen. These results suggest that the dose and schedule of IL-2 administration may influence the likelihood of response to IL-2 in renal cell carcinoma.

Phase I study of high-dose continuous-infusion recombinant interleukin-2 and autologous lymphokine-activated killer cells in patients with metastatic or unresectable malignant melanoma and renal cell carcinoma.

The current study was undertaken to determine the maximum tolerated dose of recombinant interleukin-2 (rIL-2) that could be administered as a continuous infusion in conjunction with autologous lymphokine-activated killer (LAK) cells. All 55 patients in this study received a priming dose of rIL-2 of 1.0 mg/m2 per day given as a continuous infusion over 4.5 days. Patients later received (days 11-16) one of three doses of rIL-2 per day (1.0, 1.25, or 1.50 mg/m2) in conjunction with LAK cells given on days 11, 12, and 14. Because of unacceptable toxicity occurring early in the LAK cell phase of therapy at the rIL-2 dose level of 1.50 mg/m2, we concluded that the maximum tolerated dose of rIL-2 given as a continuous infusion with LAK cells is 1.25 mg/m2 per day.

Recent advances in the management of non-Hodgkin's lymphomas.

The non-Hodgkin's lymphomas are a diverse group of diseases with distinctive natural histories and responsiveness to therapy. Each of these diseases represents the arrest and proliferation of malignant lymphocytes at a particular stage of normal lymphocyte differentiation. Cytogenetic and gene rearrangement studies have established the clonal nature of these disorders. The majority of the non-Hodgkin's lymphomas that occur in adults are of B cell origin. Exceptions to this are lymphoblastic lymphoma, mycosis fungoides, Sézary syndrome, and HTLV-1 associated leukemia--lymphomas that are diseases of T cell origin. As a group, the non-Hodgkin's lymphomas are diseases that are very responsive to radiation therapy and chemotherapy. There are major differences, however, in the durability of these responses. From a clinical standpoint, the non-Hodgkin's lymphomas may be divided into those that are indolent and those that are aggressive in their clinical behavior. Ironically, the aggressive non-Hodgkin's lymphomas are frequently curable, while the indolent non-Hodgkin's lymphomas are presently incurable in the majority of cases.