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Biomedical subjects

G Merlini

Publications and source records attributed to G Merlini.

At least 37 records · Page 2Linked to original sources

Peptichemio, vincristine and prednisone versus melphalan and prednisone as induction therapy in multiple myeloma.

Seventy-five patients with previously untreated multiple myeloma were randomly treated with the association of Peptichemio, Vincristine and prednisone (PTC-VCR-P) or of melphalan and P (MPH-P) for first induction therapy. After induction, all responsive patients received MPH and P until relapse, while unresponsive patients received it until unequivocal evidence of disease progression was observed. A second induction therapy with PTC-VCR-P was then administered, except to patients resistant to this association at first induction (who received combination chemotherapy which included cyclophosphamide and adriamycin). The response rate was 58% in the PTC-VCR-P and 41% in the MPH-P group (P greater than 0.05). The PTC-VCR-P responsive patients experienced a median duration of response shorter than MPH-P responsive patients (20.3 vs 39.7, P = 0.041). Median survival from the start of treatment was 26.2 months in the PTC-VCR-P and 54.1 months in the MPH-P group of patients (P = 0.039). Stage I and II myelomas had the same response rate to PTC-VCR-P and to MPH-P, but their survival was shorter on PTC-VCR-P than on MPH-P (P = 0.014). Stage III myelomas responded more frequently to PTC-VCR-P than to MPH-P (P less than 0.02) and there was a trend to survive longer on PTC-VCR-P than on MPH-P (22.0 vs 12.5 months, P greater than 0.05).

Antineoplastic Combined Chemotherapy Protocols

Complete remission in plasma cell leukaemia.

Two patients with primary plasma cell leukaemia who achieved complete remission are reported. They were treated with induction therapy consisting of a multipeptide derivative of sarcolysin, Peptichemio, given intravenously, combined with vincristine and/or prednisone, followed by conventional melphalan-prednisone therapy. 5-7 months following the beginning of therapy, both patients attained a complete remission which lasted 23 and 6 months; second remission was not achieved. Survival from starting therapy was 57 and 16 months respectively. These cases indicate that intravenous alkylating agents can induce a complete remission in plasma cell leukaemia similar to that achieved in other acute leukaemias.

Aged

Peptichemio, vincristine, prednisone induction treatment in multiple myeloma.

Twenty-nine patients with multiple myeloma, 16 untreated and 13 relapsing after treatment with melphalan and/or cyclophosphamide, were treated with Peptichemio (PTC), vincristine (VCR) and prednisone (PRD). The treatment was well tolerated and produced rapid resolution of bone pain and improved performance status in symptomatic patients. Rapid and marked monoclonal component reduction (greater than 50 per cent) was noted in 50% of previously untreated and 31% of previously treated patients. The median survival of previously untreated patients was 27 months, 19 months for stage III patients. Four patients resistant to common alkylating agents responded to PTC-VCR-PRD treatment and achieved long remissions (from 18 to 38 months). The therapeutic results suggest that the present combination regimen may be indicated for induction treatment of multiple myeloma patients in an advanced stage of the disease, and for treatment of myeloma patients refractory or resistant to melphalan and/or cyclophosphamide.

Adult

Rate of M-component changes and plasma cell labeling index in 25 patients with multiple myeloma treated with peptichemio.

Twenty-five consecutive patients with previously untreated multiple myeloma were studied for bone marrow plasma cell labeling index, response to peptichemio induction therapy, and rate of M-component (MC) changes during the course of the disease. They received intermittent melphalan or cyclophosphamide as maintenance therapy and peptichemio associated with vincristine at first relapse. The response rate (76%) was independent of clinical stage, evaluated according to Merlini et al and to Durie and Salmon. Among responsive patients, rapid responders (half-life of MC decrease less than 47 days for IgA and IgG and less than 29 days for light chain myelomas) had a bone marrow plasma cell labeling index significantly higher (P less than 0.01) than that of slow responders. Rapid responders had a median survival of 15 months, while slow responders had a median survival of 42 months (P less than 0.05). The difference in survival between the two groups was accounted for mainly by the difference in duration of first response and the different rates of MC increase following it. Both of these parameters were directly related to the half-life of MC decrease at response in IgA and IgG myelomas. The duration of second response and the half-life of MC increase following it were shorter than the duration of first response and than the half-life of MC increase at first relapse.

Antineoplastic Combined Chemotherapy Protocols

An IgM monoclonal protein with multiple serological specificities.

An IgM lambda M-component with a false Wasserman reaction and 'false' rheumatoid factor activity from a patient suffering from a well-differentiated lymphocytic lymphoma is presented. The monoclonal protein showed antibody activity against cardiolipin and cross-reacted with acryl particles, not with human IgG. Both these activities were found in the Fab fragment. The reduction of the 19S IgM to 7S IgM subunits was responsible for a strong decrease in activity. The importance of the IgM quaternary structure in determining antibody affinity is emphasized.

Acrylates

Long-term effects of parenteral dichloromethylene bisphosphonate (CL2MBP) on bone disease of myeloma patients treated with chemotherapy.

Data on the long-term treatment of myeloma bone disease with bisphosphonates are scanty. In a prospective pilot trial we evaluated the effect of long-term parenteral administration of dichloromethylene bisphosphonate (Clodronate), in addition to standard chemotherapy, in 30 patients with active myeloma bone disease. Patients were treated with a mean of 4 courses (range 2-8) of Clodronate: 300 mg/day i.v. for seven days followed by 100 mg/day i.m. for 10 days, administered at a mean interval of 4 months (range 3-6). The median follow-up was 24 months (range 8-36). Clodronate reduced bone pain rapidly and significantly, and reduced the mean values of the biochemical indices of bone resorption to within normal limits; these effects were maintained throughout the follow-up. In three hypercalcemic episodes serum calcium became normal after 2-5 days of treatment with Clodronate. No toxic or side effects were noticed. The occurrence of skeletal morbidity in patients treated with Clodronate was compared with that observed in the control group of myeloma patients (p less than 0.001) in severe bone pain as well as in the incidence of new osteolytic lesions and pathological fractures (p less than 0.001). Supportive Clodronate therapy contributes significantly in controlling the progression of myeloma bone disease.

Bone Diseases

Gene expression of pyrogenic cytokines in Hodgkin's disease lymph nodes.

BACKGROUND: Inflammatory cytokines released by either the neoplastic or reactive cells in Hodgkin's disease (HD) might mediate its peculiar clinical and histopathological features. We investigated by Northern blotting the gene expressions of the pyrogenic and inflammation-associated cytokines IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta (lymphotoxin) and IL-6 in 14 HD lymph nodes and studied their relation to systemic symptoms (B symptoms). METHODS: Two ug of poly(A)+RNA from 14 HD lymph nodes (8 from symptomatic and 6 from asymptomatic patients, of different histological type and disease stage) were subjected to agarose electrophoresis, Northern blotted and hybridized to the various cytokine cDNA probes. RESULTS: The inflammatory cytokines were expressed very heterogenously in HD, even in lymph nodes with the same histological type and with similar stromal inflammatory reactions. IL-1 beta was increased about 2 to 10 times in 5 of 8 lymph nodes from patients with B symptoms, whereas the other cytokines were heterogenously expressed in both symptomatic and asymptomatic patients. Statistical analysis on densitometric values demonstrated that the difference in IL-1 beta expression between symptomatic and asymptomatic patients was significant (p less than 0.02). CONCLUSIONS: These results support the hypothesis of increased IL-1 levels in tumoral lymph nodes from symptomatic HD patients.

Cytokines

Immunochemical characteristics of a particular cryoglobulin. A new cryoglobulin subgroup?

In a patient (BAR) affected by chronic active hepatitis we isolated a cryoglobulin constituted of polyclonal IgM (k and lambda) and a monoclonal IgG3 lambda. The IgM represented the antibody of the cryoglobulin complex. This type of cryoglobulin, where the monoclonal component is the antigen and not the antibody, cannot be correctly classified using the nomenclature of Brouet et al. (1) currently in use. In this patient a two-year follow-up excluded any clinical signs of cryoglobulin toxicity. The immunochemical and clinical characterization of other cryoglobulins similar to BAR could establish a new homogeneous group.

Blotting, Western

Multiple myeloma.

Multiple myeloma (MM) originates from the malignant clonal expansion of transformed B-lymphocytes (in which c-myc and ras oncogenes are probably involved). MM cells have a hybrid phenotype (with coexpression of the markers for both early and late B-differentiation and, sometimes, of T-lymphocyte, myelomonocyte, erythroid and megakaryocyte markers), which accounts for the association between MM and myeloproliferative disorders and for cytokine production. Interleukin-6 and immunologic control mechanisms regulate proliferation and differentiation into plasma cells secreting a monoclonal component (MC). Overt MM is diagnosed 1-2 years following malignant transformation. At this time, several aneuploid clones with resistant phenotype have been selected, and a small pool of actively cycling cells produces the great bulk (over 90%) of non proliferating tumor cells. The clinical and laboratory signs of MM arise from both tumor proliferation and MC damage to organs and organ systems. Tumor proliferation is mainly responsible for bone disease (since MM cells produce cytokines that activate the osteoclasts), inhibition of hemopoiesis and the appearance of plasma cell tumors. The MC causes renal failure, neurological signs, hemorrhagic manifestations. The prognosis for multiple myeloma is probably best estimated by two parameters, serum beta-2-microglobulin and the bone marrow labeling index. Induction therapy is still based on the use of alkylating agents, melphalan and cyclophosphamide, combined with prednisone. Second line treatment consists of VAD polychemotherapy or high-dose pulsed glucocorticoids. Many investigational approaches have been proposed, but their effectiveness awaits confirmation. In the absence of a curative regimen, much effort should be dedicated to the quality of supportive care. In this respect, bisphosphonates represent a new effective tool for the control of myeloma bone disease.

Antineoplastic Agents