Mantle-cell lymphoma: a population-based clinical study.

PURPOSE: From a population-based non-Hodgkin's lymphoma (NHL) registry, 41 patients with mantle cell lymphoma (MCL) -- a recently defined distinct B-cell NHL -- were selected and compared with patients with low- or intermediate-grade NHL from the same registry. PATIENTS AND METHODS: The incidence and behavior of MCL in the area of the Comprehensive Cancer Center West (CCCW) from 1981 to 1989 were analyzed. Age, performance, tumor bulk, extranodal localization, stage, response to therapy, and survival were registered. Expression of cyclin D1 protein and Ki-67 were measured in 29 patients. RESULTS: MCL made up 3.7% of NHLs. The median age was 68 years, and the male-to-female ratio was 1.6:1. Seventy-eight percent presented with stage IV, with the majority having bone marrow involvement. The complete response (CR) rate was 32% (13 of 41), with a median duration of 25 months. The median overall survival time was 31.5 months. The International Prognostic Index identified five patients with a low-risk score and a median survival time of 93+ months. In 23 of 29 patients, cyclin D1 overexpression was present, without any relation to overall or disease-free survival. In contrast, a proliferative index less than 10% was significantly related to a better overall survival time (50 v 24 months). CONCLUSION: MCL is a disease of the elderly, who present with widespread disease and with a poor response to therapy. Although it harbors features of an indolent NHL, it behaves clinically as an aggressive NHL with a short overall survival time.

Clotting factors secreted by monocytes and macrophages: analytical considerations.

The secretion of clotting factors by rat spleen macrophages and human peripheral blood monocytes has been studied. The results show that the amount of clotting factors measured depends critically upon the characteristics of the assay system used. The presence of warfarin, salicylic acid or thrombin in the culture medium is shown to decrease the vitamin K dependent clotting factor activity in the supernatant after in vitro culture of rat spleen macrophages and human peripheral blood monocytes.

The spectrum of chronic mature T-cell disorders: a report of four cases.

We describe four patients with a mature T-cell disorder. These four specific entities belong to a group formerly called "T-cell chronic lymphocytic leukaemia" (T-CLL). Nowadays we understand that these chronic T-cell lymphoproliferative disorders consist of four different entities. They stand out as well-described and separate disorders on the basis of their clinical, immunophenotypic and cytogenetic properties. Unfortunately, the majority of patients have a bad response to chemotherapy. The purine analogs may offer a better prognosis for some patients.

Sweet syndrome associated with liposarcoma: a case report.

A 36-year-old woman with a dedifferentiated liposarcoma is described who had suffered from Sweet syndrome in the past. From the literature a relationship between this syndrome and malignancy is known to exist. However, the combination of Sweet syndrome with a sarcoma has not previously been reported.

Interferon-alpha as maintenance therapy in patients with multiple myeloma.

BACKGROUND: The effect of interferon-alpha 2b (IFN-alpha-2b) on progression-free and overall survival as well as quality of life (QoL) was studied in mainly elderly patients with multiple myeloma (MM), who reached a plateau phase after melphalan/prednisone induction. PATIENTS AND METHODS: In an open phase III trial, 262 patients, median age 69 years (range 34-91), received at least 10 monthly courses of melphalan/prednisone followed by response evaluation. Plateau phase was reached by 128 patients. Next, 90 patients were randomized between IFN-alpha-2b and no maintenance therapy. Reasons for non-randomization were: refusal (18), concomitant disease (nine), protocol violation (six), WHO performance status >2 (four) and allogeneic transplantation (one) RESULTS: At a median follow-up from diagnosis of 97 months (0-140) for those patients alive, IFN-alpha-2b therapy was associated with improved progression-free survival (median 13.5 versus 8.4 months from randomization), although this did not translate in a better overall survival (41 versus 38.4 months). One-third of patients discontinued IFN-alpha due to toxicity. No differences were observed between patient groups in QoL. CONCLUSIONS: IFN maintenance therapy in MM prolongs progression-free survival and, provided that the burden of toxicity is not too high, does not adversely affect QoL.

Activation of factor VII in patients with carcinoma of the prostate. A preliminary report.

A preliminary report suggests a correlation between metastatic prostate cancer and increased plasma factor VIIa levels. Prostate cancer without metastases and prostate hypertrophy showed no clear pattern in factor VIIa. Further investigations concerning the relation between metastatic cancer and clotting factors are in progress.

Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate: its correlation with serum cortisol.

Postmenopausal patients with metastatic breast cancer were treated with aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA). Studying the interaction between the two drugs as far as plasma MPA and cortisol levels are concerned we observed a 50% decrease of plasma MPA levels after the addition of AG (P less than 0.005). With large interindividual differences in plasma MPA levels, a significant correlation with serum cortisol levels was found (P less than 0.001). It can be concluded that AG leads to a lowering of plasma MPA levels to such an extent that its adrenal suppressive effect may be diminished or even abrogated. In future trials of MPA with or without AG correlations between plasma MPA levels, serum cortisol levels and treatment response should be taken into account.

Evaluation of a coagulation assay determining the activity state of factor VII in plasma.

A coagulation assay is described that allows the measurement of the degree of activation of factor VII in circulating blood. The test is based on the use of both bovine and human brain thromboplastin, together with an artificial factor VII-deficient plasma. The latter can be prepared on a relatively large scale which makes it possible to measure factor VII activation in large series of patients. The determination of factor VII activation during incubation at 4 degrees C of plasma of women using oral contraceptives shows that the test described adequately measures factor VII activation. Differences in the time course of factor VII activation during this incubation in glass and plastic containers are found and implicate that rigorous standardization of blood sampling and test conditions is necessary. A possible mechanism that causes this critical dependence upon the test conditions is discussed.

The activity state of factor VII in plasma: two pathways for the cold promoted activation of factor VII.

The apparent amount of factor VII as determined in a one-stage test depends on the type of thromboplastin used: bovine thromboplastin only reacts with human factor VIIa whereas human thromboplastin interacts with unactivated human factor VII as well. Therefore the ratio factor VII activity as measured with bovine thromboplastin divided by the factor VII activity as assessed with human thromboplastin reflects the state of activation of factor VII in plasma. This approach was used to study the process of cold promoted factor VII activation and the involvement of different clotting factors therein. It could be shown that cold promoted activation does not occur in the absence of factors II and XII and is reduced for about 50% in factor IX deficient plasma. The other coagulation factors have a minor influence on the process. The results indicate that the cold promoted factor VII activation is the result of activation by both activated contact products and thrombin.

Phase II study of edatrexate in chemotherapy-naive patients with metastatic breast cancer.

A phase II trial of the new antifolate edatrexate (10-ethyl-10-deaza-aminopterin) was performed in thirty-eight patients with metastatic breast cancer who had never received chemotherapy. Edatrexate was administered as a weekly intravenous bolus injection at a dose of 80 mg/m2. Sites of metastases included visceral (31%), soft tissue/lymph node/bone (51%), and bone only (18%). Thirty-two patients were evaluable for response; there were 3 complete responses (CR) and 8 partial responses (PR), yielding a response rate (CR plus PR) of 34% (95% confidence limits, 17.9% to 50.9%). Responses were seen in soft tissue metastases, in visceral metastases (liver, lung) and in one patient with bone metastases. Median duration of response was 30 weeks (range 12-66 weeks). Substantial toxicity was observed. The dose-limiting toxicities were mucositis, myelo-suppression and skin toxicity. The general toxicity profile was similar to that usually reported for methotrexate, but mucositis and skin toxicity were more pronounced. Edatrexate appears to be an active drug in the treatment of chemotherapy-native patients with metastatic breast cancer.

Elderly patients with non-Hodgkin's lymphoma: population-based results in The Netherlands.

BACKGROUND: To compare characteristics, treatment and outcome of patients > or = 70 years with patients < 70 years in a population-based non-Hodgkin's lymphoma (NHL) registry. PATIENTS AND METHODS: All new patients with NHL (n = 1168) in a geographically defined region in the western part of The Netherlands were registered during a nearly 10-year period. Patient, tumour and treatment characteristics, response to therapy and survival were analysed for both age groups. An age-adjusted prognostic index was determined for elderly patients with aggressive lymphoma. RESULTS: The elderly comprised 41% of the registered patients. There were significantly more females, a preponderance of intermediate-grade histology (diffuse large B-cell lymphoma) and a lower performance status. Incomplete staging in the elderly was mostly due to the omission of a bone marrow biopsy. With respect to WF grading the complete remission rate (except for patients with low-grade/stage I NHL, patients with extranodal NHL and for patients with intermediate grade/extensive NHL) and overall survival at five years (except for patients with low-grade/stage I NHL and for patients with intermediate-grade/extensive NHL) were significantly inferior in the elderly. With respect to the R.E.A.L. Classification the exceptions were in patients with high grade MALT lymphomas (elderly good) and patients with mantle-cell and peripheral T-cell lymphomas (younger group bad too). However, once complete remission was reached, the disease-free survival did not differ significantly between the two age groups, emphasising the importance of achieving complete remission. Although 65% of the classified elderly patients presented with intermediate-grade NHL, only 26% of the elderly patients treated with chemotherapy received anthracycline-based chemotherapy. In the elderly, lymphoma (treatment-related toxicity included) contributed to death in 70% and concomitant disease (other malignancy included) in 30%, versus 78% and 22%, respectively, for the younger group (P = 0.04). The age-adjusted prognostic index, made up of the factors serum LDH, stage and Karnofsky index, showed a clear distinction between the four risk categories low, low/intermediate, intermediate/high and high, with a median survival time of 43, 20, seven and four months, respectively. For the younger group the respective numbers were 144, 45, 19 and 11 months. CONCLUSIONS: In a population-based NHL registry the elderly, predominately female patients, formed a larger proportion of the patient group than the one usually reported in the literature. In this population-based cohort inferior remission and overall survival rates were seen in the elderly. However, obtaining complete remission was beneficial for the prognosis of this disease in the elderly. By the application of the R.E.A.L. Classification important subgroups emerge.

Phase II study of recombinant interferon alpha-2a and vinblastine in advanced renal cell carcinoma.

A total of 66 patients with advanced renal cell cancer received a combination of recombinant interferon alpha-2a (18 times 10(6) units subcutaneously 3 times weekly) and vinblastine (0.1 mg. per kg. intravenously every 3 weeks). Four patients were ineligible and 6 were inevaluable for response but evaluable for toxicity. There were no complete and 9 partial responses among the 56 evaluable patients, for a response rate of 16 per cent. Median duration of response was 26 weeks, with a range of 8 to 50 weeks. Responses were observed predominantly in patients with lung and soft tissue metastases. Patients who had undergone nephrectomy did not show a better response rate than those who had not. Almost all patients had a flu-like syndrome, fatigue and anorexia. Other side effects included leukopenia, nausea, vomiting, liver function disturbances and neurotoxicity. Most of the side effects were World Health Organization grade 1 or 2; no grade 4 toxicity was observed. Antibodies against interferon developed in 6 patients during the course of treatment. However, there was no relationship between the appearance of antibodies and disease progression. The combination of recombinant interferon alpha-2a and vinblastine has modest but definite activity in patients with advanced renal cell carcinoma, although the role of vinblastine is unclear.