: Between 1968 and 1979, a total of 271 patients with advanced Hodgkin's disease received as first systemic chemotherapy MOPP (mechlorethamine [nitrogen mustard], oncovin [vincristine], procarbazine and prednisone) or COPP (as above, but cyclophosphamide instead of nitrogen mustard). In 162 of the 271 patients (60%) full remission was achieved. Demonstration of systemic signs, bioptically confirmed bone-marrow infiltration and suboptimal cytostatic dosage correlated significantly with a lower full-remission rate. A significant trend towards a lower remission rate was demonstrated for stage IV disease, in patients with lymphocyte-poor or unclassified Hodgkin's disease and in those older than 30 years. A five-year recurrence-free period was achieved in 75.5% of patients: stage of the disease and bone-marrow infiltration had a clear influence on recurrence-free survival rate. The results show that 50% of patients with advanced Hodgkin's disease can be cured by chemotherapy.

An experimental programme was conducted to investigate the conditions of microstructure and temperature necessary for the stable deformation of Ultrahigh Carbon Steel (UHCS) at very high strain rates (up to 106 s−1). Constitutive data were obtained from rod impact tests and Hopkinson bar tests over a range of strain rates and temperatures. Fracture modes were analysed, and the nature and degree of nonuniform deformation assessed. The strain-hardening behaviour was found to be strongly history-dependent as a result of solute-enhanced strain hardening in UHCS at elevated temperatures. The ductility of UHCS at high strain rates reduced at 600°C because of sharp increases in the temperature sensitivity of its strength, resulting in an increased propensity for shear banding. It is clear that changes in microstructure change the constitutive behaviour of UHCS at high strain rates.

Sequential chemotherapy with vinblastin and bleomycin, as well as adriamycin and cis-platin, was administered to 29 patients with disseminated malignant testicular teratoma. In order to intensify the induction phase, the intervals between drug administrations were individually shortened, with the next course of treatment following directly after the phase of critical leucocyte depression. This method was pursued over four courses of chemotherapy without dose reduction, followed by courses of chemotherapy in a conventional three-weekly rhythm. A response was obtained in 28 patients, 18 of them achieving complete remission. Taking into consideration unfavourable prognostic factors in the treatment group, this result is better than after the same chemotherapy at three-weekly intervals. Induction treatment adapted to leucocyte response carries with it the risk of higher toxicity, but this would seem to be acceptable in view of the improved long-term prognosis. This or similar intensification of the first treatment phase, for a long time used with leukaemias, could also be considered in the management of various chemotherapy-sensitive solid tumours, especially in younger patients.

Bone-marrow transplantations were performed in 71 patients, 11 with panmyelopathy, 17 with recurrence of acute leukaemia, 25 with acute leukaemia and remission, 18 with chronic myeloid leukaemia. The transplantation was allogenic in 67, autologous in 2, isologous in 2. Eight patients each survived in the panmyelopathy and chronic myeloid leukaemia groups. In the group of patients with acute leukaemia only one patient of those in a recurrence survived the transplantation for several years, but after 6 years there was another recurrence. Of the 20 patients with acute myeloid leukaemia who received the transplantation during their first remission, 11 are still alive. Retransplantation because of the recurrence was employed in one case each of acute and chronic myeloid leukaemia. Main cause of death was interstitial pneumonia with an overall risk of 23%. Only 5% of patients developed severe acute graft-versus-host reaction, grades III-IV. The low incidence of this reaction is possibly due to the strict gnotobiotic measures which in most of the patients led to decontamination of the intestinal tract.

Combined treatment with adriamycin, cyclophosphamide and vincristine (ACO) was used in 50 out-patients with histologically verified small-cell bronchial carcinoma. In 26 patients with locally and regionally limited metastases ("limited disease") radiotherapy (3000 rad focal dose) to mediastinum, hili and tumour opacity as well as prophylactic cranial irradiation (3000 rad focal dose) were performed after 3 cycles of chemotherapy. Complete clinical remission (without endoscopic control) was achieved in 32 out of 50 patients. Remissions in patients with bilateral pulmonary or extrathoracic metastases ("extensive disease", n = 24, 12 complete remissions) only led to limited asymptomatic prolongations of life (median survival time 10 months, median remission period 5 months) despite maintenance therapy. On the other hand patients with "limited disease" had considerable life prolongation (median survival 21 months, historical control value 3--4 months). Seven out of 26 patients in this group survived for 30 months after the onset of the disease, 6 out of 26 are now in their third year after starting therapy without signs of tumour recurrence. The results show that early recognition of patients with local and regional metastases has considerable prognostic value.

Interferon (IFN-alpha 2 B) was administered to 21 patients with chronic myeloid leukaemia (CML), at an initial dose of 4 X 10(6) IU/m2 daily subcutaneously, adapted to changes in leukocyte count in the course of treatment. Of 16 patients that could be fully evaluated (12 males, 4 females; aged 21-64 years), 15 were in the chronic phase, one had a blast crisis. "Haematological remission" was achieved in nine of the 16 patients, while in the remainder, with one exception, transitory reduction in leukocyte count was obtained. With pretreatment counts of 18-151 X 10(9)/l, normalization to 2.7-6.9 X 10(9)/l was achieved in 13 patients after 3-40 weeks. In parallel to these effects there was a decrease in platelet count (before treatment 86-1550 X 10(9)/l to 30-279 X 10(9)/l after an average of six weeks) and in lactate dehydrogenase (initially 220-958 U/l to 87-232 U/l after 3-33 weeks). A reduction in Philadelphia chromosome-positive metaphases by as much as 50% was observed in four of eight patients. Administration of IFN-alpha 2 B achieved a relatively rapid cell reduction in the chronic phase of CML. The long-term effect on the course of the disease and the place of IFN in the overall concept of CML treatment remains unanswered.

In a 44 year old patient with chronic lymphatic leukemia and secondary antibody deficiency syndrome, a disorder of articulation and a left hemiparesis developed during a thrombocytopenic phase. Computer tomography of the cranium, CSF diagnostics and the electroencephalogram did not provide any indication for the cause of the rapidly progressive cerebral symptoms. In the NMR tomogram, a diffusedly increasing intensity in the T2-weighted tomograms were shown around the central region in the right brain. The patient died of a Pseudomonas septicemia. At autopsy, a typical finding of progressive multifocal leukoencephalopathy was found in the areas altered in the NMR tomography. Papova-like virions could be demonstrated in glial cells by electron microscopy.

We study the critical values of the complex standard-L-function attached to a holomorphic Siegel modular form and of the twists of the L-function by Dirichlet characters. Our main object is for a fixed rational prime number p to interpolate p-adically the essentially algebraic critical L-values as the Dirichlet character varies thus providing a systematic control of denominators of critical values by generalized Kummer congruences. In order to organize this information we prove the existence of p-adic measures such that integration of any Dirichlet character of p-power conductor over the measure yields the suitably normalized critical value of the complex L-function twisted by the Dirichlet character. In a standard manner the p-adic measures naturally define p-adic L-functions which hence p-adically interpolate the normalized critical values.

A total of 51 fully evaluable patients with advanced and intensively pretreated breast cancer were treated with a combination chemotherapy of ifosfamide plus mesna, methotrexate and 5-fluorouracil. All patients had received at least one series of combined chemotherapy, 30 patients had received more than one combination and 41 patients had had anthracyclines before. Metastatic lesions in more than one site were found in 42 patients, and 24 patients had metastatic liver lesions. Partial remission was achieved in 10 patients (20%) and no change in 16 patients (31%). Survival was almost identical in both groups of responding patients and significantly shorter in treatment failures. Response was favorable in patients without pretreatment with anthracyclines. Two patients who received this protocol directly after progression with cyclophosphamide, methotrexate and 5-fluorouracil (CMF protocol) responded with a partial remission. Median time to progression was 7 months for partial responders and 4.5 months for patients achieving a no-change status. Median survival was 8 months for all patients. Toxicity was tolerable. Leukocytopenia and thrombocytopenia were treatment-limiting parameters. Overall, this protocol is well tolerable and effective in breast cancer patients with advanced disease and in intensively pretreated patients.

The prognosis of patients with refractory or relapsed malignant lymphoma is poor. To improve the outcome of such patients, a therapeutic regimen of VIM +/- B (etoposide/ifosfamide plus mesna/methotrexate/ with or without bleomycin) was administered. Of 47 patients treated, 15 had relapsed following complete remission (CR) after first-line chemotherapy, 28 had failed to achieve CR with first-line therapy, and four failed to respond to multiple salvage regimens. All patients had received extensive prior chemotherapy, and 36 had received combinations containing doxorubicin. Eight patients had low-grade non-Hodgkin's lymphoma (NHL), 28 had high-grade NHL, and 11 patients had Hodgkin's disease. Overall response rate was 87%, with 45% CR and 42% partial remission (PR). Median relapse-free interval was 8 months in patients with CR and 6 months in those with PR. Of patients with CR, 43% were predicted to be without relapse at 2 years and 31% at 5 years. Median survival time for all patients treated with 14 months-22 months for those with CR and 10 months for those with PR. Probability of survival at 2 years was 30% in all patients, 50% in patients with CR, and 15% in those with PR. VIM +/- B appears to be effective against refractory or recurrent lymphoma, resulting in response in a large number of patients and long-term survival and possible cure in a small but significant number. Results indicate that VIM +/- B is particularly effective in patients with high-grade NHL who have responded suboptimally to primary therapy.

In four patients (a 54-year-old man and three women aged 57, 60 and 65 years, respectively) with colorectal carcinoma and no obvious cardiac abnormality anginal symptoms and ECG changes occurred during chemotherapy with 5-fluorouracil at a dose of 400 and 600 mg/m2. The ECG changes consisted of descending ST depressions with preterminally negative T waves, terminally negative T waves, ventricular extrasystoles and sinus tachycardia with intermittent atrial fibrillation. The signs first appeared between the second and fourth day of treatment; in two patients they improved with glyceryl trinitrate. A few days after 5-fluorouracil had last been administered all ECG changes had disappeared. The causes of cardiotoxicity of the drug remain unknown.

This paper reports on seven atypical Philadelphia chromosome translocations in chronic myelocytic leukemia. Three of them, a t(16;22), t(17;22), and t(9;14;22) have already been observed before, while the t(X;9;11;22), t(X;22), t(3;22), and t(3;4;9;22) are newly reported.

Thirty-five patients with a median age of 55 years (range, 28 to 68 years) and a median Karnofsky status of 80% (range, 40% to 100%) were treated with ifosfamide (1.5 g/m2 plus mesna), methotrexate (40 mg/m2), and 5-fluorouracil (600 mg/m2) intravenously (IV) days 1 and 8 at intervals of 4 weeks. Thirty-four patients had received previous chemotherapy, including anthracyclines in 28 patients. All patients were evaluable for response. A partial remission was achieved in six patients (17%), stable disease in 13 patients (37%), and 16 patients (46%) were unresponsive. Median time to progression was 7 months (range, 4 to 13 months) for partial responders, and 4 months for patients with stable disease. Median survival was 9 months for all patients, 13 months for partial responders, 16 months for no change, and 3 months for progressive disease. Toxicity was tolerable, with myelotoxicity being a dose-limiting factor, mainly in heavily pretreated patients. No treatment-related death occurred. In conclusion, this combination is effective and well tolerated. Ifosfamide is suggested for further evaluation in advanced breast cancer.