Cyclophosphamide plus vincristine and prednisone in the treatment of severe pemphigus vulgaris refractory to conventional therapy.

Five patients with severe pemphigus vulgaris refractory to conventional therapy with azathioprine and corticosteroids were treated with cyclophosphamide, vincristine and prednisone. One patient was not evaluable, while the remaining four patients showed a complete response. Duration of response was in the range of 13-94 months. Toxicity was mainly represented by alopecia, myelosuppression and gastrointestinal side-effects such as nausea/vomiting. Although cyclophosphamide and vincristine may induce severe side-effects, this association may be useful in controlling severe disease resistant to previous conventional therapies.

The in vivo effects of recombinant human erythropoietin on cisdiamminodichloroplatinum-induced anemia in golden Syrian hamsters.

Recombinant human erythropoietin given subcutaneously is able to accelerate hematopoietic recovery in hamsters affected by cisplatin-induced anemia, increasing hemoglobin and hematocrit levels. The increase in hemoglobin and hematocrit levels. The increase in hemoglobin and hematocrit levels is not accompanied by an increase of platelet or granulocyte counts in the peripheral blood. However, an increase in the marrow concentration of burst and colony forming units--erythroid (BFU-E, CFU-E) is observed after recombinant human erythropoietin treatment. This increase in the concentration of marrow erythroid progenitors was accompanied by an increase in the percentage of these stem cells in DNA synthesis as assessed by exposure to ARA-Cyt. Recombinant human erythropoietin seems highly effective in ameliorating and/or preventing cisplatin-induced anemia in experimental animals.

The effects of the macrocyclic lactone bryostatin-1 on leukemic cells in vitro.

The macrocyclic lactone bryostatin-1 was found to exert in vitro antineoplastic activity against several leukemic cell lines, including human K562 erythroleukemia, HL60 promyelocytic leukemia, REH and MOLT-4 lymphoblastic leukemias, CCRF-CEM lymphoma, KG-1 myeloid leukemia, and murine P388 lymphocytic leukemia. No statistically significant difference in sensitivity to bryostatin-1 was found between adriamycin-resistant P388 and K526 subclones and their sensitive counterparts. Freshly explanted clonogenic leukemic cells showed a variable sensitivity to bryostatin-1 in 10/12 tested samples. The IC50 of clonogenic leukemic cells was 4 x 10(-3) M bryostatin-1, and that of normal marrow CFU-GM was 10(-5) M. Leukemic cells exposed to bryostatin-1 showed a variable degree of monocytic differentiation as evaluated by ANAE staining and morphology. Bryostatin-1 is also able to inhibit the growth of CFU-GM from myelodysplastic marrow and to shorten the duration of dysplastic hematopoiesis in liquid culture. In conclusion, these data suggest that bryostatin-1 is a potent antileukemic agent in vitro that may be potentially useful for clinical studies.

[Correlation of some instrumental, metabolic and clinical parameters in cerebral atherosclerosis]. / Correlazione di alcuni parametri strumentali, metabolici e clinici nell'aterosclerosi cerebrale

The epidemiological, clinical and instrumental features of cerebral circulatory insufficiency are examined in an assessment of the criteria required for correct diagnosis. The need to refer to both direct and indirect criteria is illustrated in the light of a series of cases. From the 4th decade of life onwards, males are more prone to cerebral arteriosclerosis. Hypertension, diabetes and obesity are significant risk factors. The findings obtained by various methods of examination are critically discussed. Their correct interpretation naturally demands correlation with the clinical data.

Prospective, randomized trial of sequential interleukin-3 and granulocyte- or granulocyte-macrophage colony-stimulating factor after standard-dose chemotherapy in cancer patients.

BACKGROUND AND OBJECTIVE: Several in vitro and animal studies have shown that IL-3 primes hematopoietic stem cells to become more sensitive to later acting growth factors. We wanted to compare the toxicity and the synergistic stimulatory effect of interleukin-3 (IL-3) followed by granulocyte colony-stimulating factor (G-CFS) or granulocyte-macrophage colony-stimulating factor (GM-CSF) on white blood cell (WBC) and platelet counts, after standard-dose chemotherapy (CT) in patients with solid tumors. DESIGN AND METHODS: Fifty consecutive cancer patients with thrombocytopenia and/or leukopenia registered during a previous course of CT were randomized to receive, after the following course, IL-3 (10 microg/kg/day, s.c., day 1-5) followed by G- or GM-CSF (5 microg/kg/day, day 6-8). RESULTS: The nadir of WBC in the cycles supported with the combination of IL-3 and G-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p < 0. 005). Furthermore, severe leukopenia was abrogated in all the cycles supported with IL-3+G-CSF, while in the cycles without cytokines, this event was registered in 62.5% of the cases (p < 0.0005). Finally, the recovery of WBC was achieved a mean of 4 days earlier in the cycles supported with IL-3+G-CSF. As for thrombocytoprotection, no significant differences were evidenced, but severe thrombocytopenia was abrogated in all the cycles supported by IL-3+G-CSF (p < 0.05). Furthermore, platelet recovery after CT was achieved on average 3.5 days earlier in the IL-3+G-CSF group than in the previous cycles. The nadir of WBC count in the cycles supported by the combination of IL-3 and GM-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p < 0.005). Furthermore, severe leukopenia was abrogated in 40% of the cycles supported by IL-3+GM-CSF, while in the cycles without cytokines, this event was registered in 80% of the cases (p < 0.005). Finally, the recovery of WBC was achieved a mean of 3.5 days earlier in the cycles supported by IL-3+GM-CSF. As far as thrombocytoprotection is concerned, there were no significant differences in the nadir between the cycles supported by the association IL-3+GM-CSF and the cycles not supported by cytokines. However, severe thrombocytopenia was registered in 20% of the cycles not supported by growth factors but in only 10% of the cycles supported by IL-3+GM-CSF (p < 0.05). Furthermore, platelet recovery after CT was achieved on average 3 days earlier in the IL-3+GM-CSF group. The combination of IL-3 and G-CSF would appear to be more effective than the combination of IL-3 and GM-CSF in the control of both severe thrombocytopenia and leukopenia. Indeed, severe leukopenia was abrogated in all the cycles in arm A, but only in 40% of the cycles in arm B (p < 0.0005). Furthermore, considering a platelet count below 49

Analysis of human dysplastic haematopoiesis in long-term bone marrow culture.

In this paper we have analysed the behaviour of myelodysplastic marrow in a long-term bone marrow liquid culture system (LTBMC) from eleven patients with myelodysplastic syndromes with regard to cellularity, day-7 and day-14 CFU-GM growth, cluster formation, adherent cells and CFU-F formation. An altered CFU-GM pattern was found in 64% of cases at diagnosis, while normal growth was seen in the remaining cases, all of which were affected by refractory anaemia. The levels of CFU-GM, as well as cellularity, were reduced in myelodysplastic marrows compared to normal controls over the whole duration of LTBMCs. Cases with a normal CFU-GM level at diagnosis also showed pathological behaviour when examined in LTBMC. The duration of dysplastic haematopoiesis was significantly shorter than that of controls. The proliferative ability of CFU-F was reduced in 50% of cases as shown by replating experiments. In conclusion, myelodysplastic marrow shows an abnormal behaviour in LTBMC, even in those cases which present normal CFU-GM growth at diagnosis.

Soluble interleukin-2 receptor in vitro production by mononuclear cells from Hodgkin patients.

Lymphocytes of patients with Hodgkin's disease have a deficient production of Interleukin-2. Recently, a soluble form of the receptor for IL-2 has been demonstrated in human sera and in vitro-stimulated culture supernatants from human T lymphocytes. In the present paper we report the production of soluble IL-2R from peripheral blood mononuclear cells in H.D. The unstimulated MNC of patients released more sIL-2R than controls. No difference was observed between PHA-stimulated MNC of patients and controls. These preliminary findings suggest that soluble IL-2R may be provide a new tool for the study of immunological dysregulation in H.D.

Effect of alpha IFN on unaggressive immunoproliferative disorders.

BACKGROUND: alpha-IFN is reported to be an effective treatment for a number of lymphoproliferative diseases. Little information is available at present on its effect in unaggressive immunoproliferative disorders. STUDY DESIGN AND RESULTS: In a prospective non randomized study, 57 patients with IgG or IgA MGUS, smouldering myeloma or stage I MM treated with alpha-IFN (3 MU 3 times a week for at least 6 months) were compared to 129 untreated similar patients. Four patients in the IFN group showed a monoclonal component reduction > 50% versus none in the control group, and 25% of patients suffered disease progression (MC increase > 50% and/or osteolytic lesions) in the IFN group as compared to 18% in the control group. CONCLUSIONS: alpha-IFN administration at the dose used is ineffective for the majority of patients with slowly proliferating immunoproliferative disorders; only a small subgroup of them may benefit from such a treatment.