Time course of urinary neopterin in a non-Hodgkin's lymphoma patient during chemotherapy and radiotherapy.

The objective of this study was to follow urinary neopterin in a patient affected by non-Hodgkin's lymphoma during the three months treatment from the onset of the disease. In the study a patient affected by non-Hodgkin's lymphoma in Stage IV (centrocyto-centroblastic type) was enrolled. He was treated with combined chemotherapy and local radiotherapy. Neopterin was measured by high performance liquid chromatography in the first morning urine specimens. The time course of urinary neopterin levels ranged from 110 to 524 micromol x mol(-1) creatinine (mean 261, SD 67.5 micromol x mol(-1) creatinine). Over 70 % of the received values were higher than the upper limit of normal excretion of healthy subjects. Longitudinal analysis showed a relatively big variance of urinary neopterin with a tendency of decrease during the treatment. The significant decrease of urinary neopterin was observed till after the radiotherapy period which followed the chemotherapy period. In conclusions, the response to the therapy was accompanied by a reversal tendency of neopterin excretion to physiological values. This study confirms neopterin as a suitable additional parameter for the control of non-Hodgkin's lymphoma therapy.

Radiotherapy of early stages Hodgkin's disease. 10 years experience of the Masaryk Memorial Cancer Institute.

Radiotherapy and chemotherapy, alone or in combination, are curative treatment methods in early stages of Hodgkin's disease (HD). The choice of treatment depends on the stage of the disease, histological type and localization of the tumor, as well as on other prognostic factors. A retrospective study was conducted including 145 patients with clinical Stages I and II of HD according to Ann Arbor classification, all treated in the Masaryk Memorial Cancer Institute in Brno during the years 1985 through 1994. 80 patients were males (55%) and 65 patients females (45%). The age of the patients ranged from 11 to 77 years, with an average of 34.8 years. 41 patients were diagnosed with Stage IA tumor, 1 patient with Stage IB, 75 patients with Stage IIA and 28 with Stage IIB disease. The histological types of the disease were lymphocyte predominant in 23 patients, nodular sclerosis in 49 patients, mixed cellularity in 65 cases and lymphocyte depletion in 8 cases. 91 patients were treated with radiotherapy alone. In this group 14 patients relapsed within the radiation field (15%) and 25 outside the radiation field (28%). 39 patients were treated with combination of radiotherapy and chemotherapy. In this group relapse occurred within the radiation field in 3 patients (8%) and outside the radiation field in 7 patients (18%). 15 patients were given chemotherapy alone, 7 patients from this group experienced a relapse. The five-year survival was 81% in patients with Stages IA and IIA disease, 65% in Stages IB and IIB disease. The five-year survival in the patients who relapsed was 56%. Radiotherapy remains the curative method of choice in highly selected group of patients with early stages of Hodgkin's disease. The results of radiotherapy alone are unsatisfactory in unselected clinical Stage I--II patients because of the presence of patients with adverse prognostic factors, particularly B symptomatology, mixed cellularity/lymphocyte depletion histology, higher age. These patients are candidates for combined treatment. Modern equipment and meticulous treatment are conditions crucial for the outcome of curative radiotherapy in patients with Hodgkin's disease. Combination chemotherapy is very effective in the treatment of relapse following the primary radiotherapy.

Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.

[Erythema exsudativum multiforme with macroglobulinemia]. / Erythema exsudativum multiforme s makroglobulinémií.

A case of a 47-year-old man with skin lesions of erythema multiforme and macroglobulinemia is reported. Histological changes corresponded with mixed dermoepidermal type of erythema multiforme and direct immunofluorescence showed fibrillar band with anti-IgM and anti-fibrin on basement membrane. Further examination revealed serum monoclonal IgM kappa with traces in urine. Association or coincidence of these findings is discussed.

[Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group]. / Lécba mnohocetného myelomu vysokodávkovanou chemoterapií s transplantací autologních kmenových hemopoetických bunek a následující udrzovací lécbou interferonem alfa-2b nebo interferonem alfa-2b a dexametazonem. Zpráva o probíhající studii "4w" Ceské myelomové skupiny.

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.

[Fatty acid and cholesterol crystals in bone marrow smears of oncology patients]. / Krystalky mastných kyselin a cholesterolu v rozteru kostní drene u onkologických nemocných.

In 50 haematological-oncological and oncological patients the authors found in bone marrow smears fatty acid and liquid cholesterol crystals. The number of crystals of fatty acids does not correlate directly with the triacylglycerol serum levels. Similar findings were recorded also in haematological patients.

Docetaxel vs mitomycin plus vinblastine in anthracycline-resistant metastatic breast cancer.

This nonblinded, multicenter, randomized phase III study compares the median time to progression (primary endpoint), response rate, and quality of life, safety, and survival of docetaxel (Taxotere) vs mitomycin (Mutamycin) plus vinblastine (Velban) in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. Patients were randomized to receive an intravenous infusion of either 100 mg/m2 of docetaxel for 1 hour every 3 weeks, or 12 mg/m2 of mitomycin every 6 weeks plus 6 mg/m2 of vinblastine every 3 weeks. This preliminary analysis presents data on 200 patients among 392 patients recruited. Median time to progression was longer in the group treated with docetaxel compared with the mitomycin/vinblastine group (17 vs 9 weeks). The overall response rates were higher with docetaxel (28% vs 13%, respectively), and fewer patients in the docetaxel group had progressive disease as their best overall response (29% vs 48%). As expected, thrombocytopenia was more common in the mitomycin/vinblastine group, and neutropenia occurred more frequently in the docetaxel group. Severe fluid retention in the docetaxel group (8.7%) resulted in treatment discontinuation in 5 patients (5%). Severe thrombocytopenia (12%) and constipation (6%) led to treatment discontinuation in 7 and 3 patients, respectively, in the mitomycin/vinblastine group. Based on this preliminary analysis, docetaxel appears to be equally as safe as and more active than mitomycin/ vinblastine in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. These results are subject to cautious interpretation because this analysis was conducted on the first 200 patients who finished the study treatments, and these preliminary results may underestimate response and overstate treatment discontinuation rates. Thus, the final analysis on the entire patient population is necessary to confirm these preliminary findings.

High dose alpha-2-recombinant interferon in the treatment of malignant lymphoproliferative diseases. A pilot study.

In the presented clinical study, 10 patients with malignant lymphoproliferative diseases (2 with acute lymphoblastic leukemia, 3 with Hodgkin's disease, and 5 with non-Hodgkin's lymphoma), resistant to standard therapy, were administered alpha-2-recombinant interferon at a dosage of 120 x 10(6) IU as a continuous 48 h i.v. infusion. The second administration was performed after an interval of 1 month. A therapeutic response was seen in 50% of the patients, of them there were two complete remissions (in the two acute lymphoblastic leukemia patients) and 3 partial remissions (in 2 patients with Hodgkin's disease and in 1 patient with low malignant non-Hodgkin's lymphoma). In four patients with high malignant non-Hodgkin's lymphomas the treatment did not evoke any response, and in 1 patient with the same diagnosis progression was noted after the treatment. The toxic effects of the drug were in accord with literature data, and although high doses of alpha-2-recombinant interferon were administered, it was not necessary to interrupt the treatment in any of the patients. Considering the therapeutic effect of this immunomodulator used in the treatment of malignant lymphoproliferative diseases, our results are promising, nevertheless further studies will be required.

Alteration of beta-2-microglobulin level in malignant lymphoproliferative diseases after a high dose of alpha-2-recombinant interferon.

A group of 10 patients with malignant lymphoproliferative diseases resistant to any standard therapeutical modalities were treated with a high dose of alpha-2-recombinant interferon (alpha-2-rIF). Alpha-2-rIF was administered at a total dose of 120 x 10(6) IU in a continuous infusion during 48 h. Two cycles of alpha-2-rIF immunotherapy were employed with an interval of 1 month in between each. Serum and urinary beta-2-microglobulin (B2M) were examined prior to alpha-2-rIF application and on days 2, 4, 6 afterwards. Alpha-2-rIF treatment induced an increase in serum B2M as noted on day 2 followed by a decline to below the normal range. The initial increased value was significantly higher as compared to either the pretreatment value or the normal physiological range. The reduced B2M serum level was protracted and lasted until the second cycle of treatment. Similar but not so great changes in B2M serum values were noted during the second application of alpha-2-rIF. The changes of B2M level in the urine, although less convincing, mimic those observed in the serum. The present results confirmed the biological activity of alpha-2-rIF in malignant lymphoproliferative diseases.