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Thirty adult patients with lymphoblastic lymphoma were treated with two different programs according to bone marrow findings. Bone marrow positive patients were given an ALL-like program: vincristine, daunorubicin, cyclophosphamide and prednisone for induction of remission, CNS prophylaxis, continuous maintenance for three years and monthly reinductions. Bone marrow negative patients were given a conventional lymphoma program with CHOP-Bleo and limited RT on bulky mediastinum without CNS prophylaxis. The CR rate of the whole group was 54 % (62 % for ALL-treated versus 47 % for lymphoma-treated patients; not significantly different), with a median survival for remitters of 28.5 mos. Relapse-free survival of the whole group was 65 % at 12 and 25 % at 24 mos. Stage IV ALL-treated patients had a median survival of 16.5 versus 10 mos for stage IV lymphoma-treated ones (p = 0.05); the three-years survival was 24 and 10 %, respectively. No patients undergoing CNS prophylaxis (ALL-therapy) had neurological complications or late meningeal relapse. The better prognosis of ALL-treated patients, in spite of bone marrow positivity, argues in favor of an ALL-like therapy in all adult lymphoblastic lymphomas, in terms of CR rate, overall survival, and absence of CNS relapse. This therapy must be adopted irrespective of bone marrow findings, and regardless of how localized the lymphoma appears to be.

We reviewed 182 consecutive adult patients with low-grade malignancy, non-Hodgkin's lymphomas classified according to the Kiel classification, followed at the Division of Hematology, Policlinico S. Matteo, Pavia, from January 1975 to December 1981, to recognize, in each histopathologic type, important subgroups from the prognostic standpoint. Median follow-up was 36 months. No significant differences were observed in the response rate to conventional therapy (radiotherapy for localized disease, CVP for advanced stages) between the 4 cytologic types. The centrocytic-centroblastic lymphoma with diffuse nodal architecture showed an intermediate-grade malignancy (median survival, 50 months) and underwent cytologic progression to the high-grade malignancy centroblastic type in 10% of the cases. Large-cell centrocytic and polymorphic lymphoplasmacytoid lymphomas had a poor prognosis (median survival less than 30 months) when treated with conventional therapy for favorable histologies, and 6% of the cases transformed into the high-malignancy immunoblastic type. Patients with lymphocytic lymphoma with bulky mediastinum had a median survival of 20 months. The identification of these subgroups with a worse prognosis may have therapeutic implications.

Cutaneous and visceral dissemination of Kaposi's sarcoma (KS) occurred in a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) who had been treated with combination chemotherapy. Three other cases of KS complicating immunosuppressive therapy of AILD have been reported in the literature, and there is evidence to indicate that AILD displays features which are known to predispose to KS. Like in other subjects with profound immunodeficiency (e.g. in young homosexual men), in our patient KS pursued an unusually aggressive course, with involvement of lymph nodes and internal organs as well as the skin. It is concluded that the risk of developing severe KS is a further reason to avoid aggressive combination chemotherapy in patients with AILD, particularly in those of Jewish or Mediterranean ancestry. Even the use of corticosteroids should be reduced to a minimum to avoid immunosuppression, and a conservative approach to treatment seems advisable.

Fifty-eight patients with immunoblastic lymphoma (IBL) were the object of this study. Fifteen of them (26 %) developed IBL during or after other diseases, either immunologic or neoplastic, including angio-immunoblastic lymphadenopathy, autoimmune disorders, chronic lymphocytic leukemia, Waldenström's disease, lymphoplasmacytoid lymphoma and Hodgkin's disease (subsequent IBL). The comparison between de novo and subsequent IBL revealed a significantly higher incidence of bone marrow involvement and bulky abdominal disease in the latter group, with a lower response rate to chemotherapy. The favorable primary extranodal disease of Waldeyer's ring exclusively belonged to de novo IBL, whereas the frequency of immunoglobulin abnormalities was higher in the subsequent IBL group (67 %). The stage of disease, systemic symptoms at diagnosis and response to therapy were predictive of survival. The overall complete remission (CR) rate in the whole series was 37 % and the median overall survival 14 months. Complete remitters have a median survival in excess of 60 months; all relapses occurred within the first 12 months of CR. No CNS relapse terminated the CR, and CNS prophylaxis seems unnecessary in IBL. The analysis of subsequent IBL may provide information on the pathogenesis of non-Hodgkin's lymphomas; the still poor prognosis of IBL deserves new therapeutic attempts to improve on the standard regimens.

Heart lesions induced in mice, rats, rabbits and dogs by Doxorubicin administered i.v. according to various schedules were studied by light and electron microscopy. Vacuolization of myocardial cytoplasm due to distention of the sarcoplasmic reticulum, the T-tubule system and the Golgi vesicles was one of the most common findings. Myocytolysis, clumping and loss of fibrils, fragmentation of sarcomeres, swelling of mitochondria and an increase in lysosomes and residual bodies were also observed. The severity of the cardiomyopathy, quantitatively evaluated by a score system, proved to be dose-dependent. Cardiomyopathy was more severe when the treatment was given in a short period by administration of high doses than when the same cumulative dose was administered as low doses repeated for a long period. The left atrium was more severely affected than the ventricles when high doses were given, whereas it was less affected in animals given low doses. The cardiomyopathy was less severe in animals receiving the same dose in a high volume of solvent and during a long perfusion time. Threshold doses were needed both to induce the cardiomyopathy and to establish it as a progressive disease.

In rats repeatedly treated subcutaneously as infants with adriamycin in 2 cycles of 4 treatments each, the induction of ocular and dental abnormalities and tumors was studied. Cataracts appeared from 18 to 26 days in 80 % of CD rats treated with 1.15 mg/kg/day of adriamycin and from 28 to 104 days in 55 % of Wistar-Lewis rats given 0.75 mg/kg/day adriamycin. Abnormal growth of incisors was observed in 30 % of the CD rats and in 44 % of the Wistar-Lewis rats. At lower doses, no such abnormalities were found. At about 1 year after treatment, 100 % of the CD rats treated with 0.75 mg/kg/day adriamycin and about 60 % of the Wistar-Lewis rats treated with 0.75 and 0.5 mg/kg/day adriamycin developed tumors, which were histologically classified.