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Biomedical subjects

M Cavo

Publications and source records attributed to M Cavo.

At least 73 records · Page 4Linked to original sources

Improvement of human myeloma stem cell growth in a liquid culture system supplemented with phytohemagglutinin.

A highly efficient cloning system for in vitro myeloma colony growth could be valuable for screening antineoplastic agents in resistant patients and for testing the effects of purging methods in the context of autologous bone marrow transplantation. In this paper we report the results of experiments intended to improve the myeloma cloning system in plasma clot originally described by Ludwig et al. We tested the effects of the addition of phytohemagglutinin (PHA), coupled with a transformation of the original plasma clot method into a liquid culture system. A statistically higher number of myeloma colonies was observed in the liquid system in the presence of PHA (20 cases, median 84.5 vs. 9.5; p = 0.005), whereas a single variant (either PHA alone or liquid system alone) did not determine any significant growth variation. The increase in the cloning efficiency was evident even in the cases characterized by low bone marrow plasma cell infiltration, suggesting that this method is suitable for the described purposes.

Bone Marrow Cells↗

M-2 protocol for melphalan-resistant and relapsing multiple myeloma.

33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M-2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumour cell mass reduction (greater than or equal to 50%) was achieved in 17% of the patients (6% of previously nonresponders and 33% of previously relapsing), while 9 additional patients improved (30-50% tumour reduction), for an overall response rate of 47% (39% for previously nonresponders and 58% for previously relapsing). The median duration of response was 7 months. Thrombocytopenia was the most common toxicity encountered in the study (39% of cases). Our findings indicate that M-2 protocol is an effective salvage treatment for patients who relapse from previous chemotherapy with alkylating agents. In contrast, results in patients who are primarily resistant to these drugs justify the search for different treatment programmes which can produce greater degrees of tumour reduction.

Adult↗

Cyclosporin A in the treatment of CLL associated PRCA and bone marrow hypoplasia.

Three patients (1 PRCA-T-CLL, 1 PRCA-B-CLL, 1 B-CLL aplasia) were treated with cyclosporin A (CS-A). Patient no 1 had relapsed during steroid therapy and the remaining two patients had been resistant to conventional immunosuppression. CS-A produced in all cases a prompt remission (within 1-4 weeks) of bone marrow failure. Mild reversible renal toxicity was the only side-effect noted. CS-A might be tried in every case of CLL-associated bone marrow failure.

Adult↗

Normal and neoplastic plasma cell membrane phenotype: studies with new monoclonal antibodies.

Three monoclonal antibodies (MoAb), named 8A, 8F6 and 62B1, reacting with plasma cell-associated antigens, were characterized. 8A was found to be positive throughout the B cell lineage maturation steps from the immature B-committed CD10+ cell to the plasma cells. 8F6 and 62B1 reactivity is restricted to more mature cells and related lymphoid malignancies. In particular 62B1 appears to be limited to hairy cells and plasma cells. The results show that it is possible to obtain reagents reacting with plasma cells by immunizing mice with cells derived from human multiple myelomas. Furthermore, the obtained results suggest that it is possible to elicit antibodies against antigens which are present throughout all the differentiation steps of the B cell lineage. These new MoAb could help in elucidating the phenotype of the plasma cells and the relationships of multiple myelomas with other B cell proliferative disorders.

Animals↗

Bone marrow transplantation in multiple myeloma.

We report 3 cases of allogeneic bone marrow transplantation in multiple myeloma that we have recently performed. Following conditioning treatment with i.v. cyclophosphamide (60 mg/kg/d, for 2 d), oral melphalan (1.0 mg/kg/d, for 5 d), i.v. BCNU (5.5 mg/kg, in a single dose) and total body irradiation (10 Gy in a single fraction) we observed in all 3 cases the disappearance both of serum M component and of monoclonal bone marrow plasma cells. 1 patient died of acute GVH disease, grade IV, at 2 months, while the other 2 patients are in good health and in unmaintained complete remission at 4 and 20 months, respectively. The usefulness of allogeneic bone marrow transplantation in the management of multiple myeloma is emphasized.

Adult↗

Solitary plasmacytoma of the bone in a case of Hodgkin's disease.

This report describes a case of solitary plasmacytoma of the bone which occurred in a 35-year-old male 3 years after mantle field irradiation for Hodgkin's disease, nodular sclerosing, stage IA. The possible significance of this rare association is discussed.

Adult↗

Renal failure in multiple myeloma. A study of the presenting findings, response to treatment and prognosis in 26 patients.

The presenting clinical features, response to treatment and survival duration of 26 consecutive multiple myeloma patients with renal failure at diagnosis were investigated. All but 1 of the patients had high tumour cell mass stage, as identified by one (3 cases) or more (22 cases) of the criteria defined by Durie and Salmon. Survival length of azotaemic patients was significantly shorter than that of stage III patients with normal renal function (median: 4 months vs 41 months, respectively, P less than 0.0005), and was positively affected by reversal of renal failure following treatment (P less than 0.0005). Of the 26 patients, 56% achieved reversal of renal failure. Recovery of normal renal function was prompt in most of the cases and appeared to be independent from both M component type and pretreatment serum creatinine levels. Finally, it was shown that patients with reversible renal impairment but with myeloma unresponsive to alkylating agents had early recurrence of impaired renal function and a shorter life expectancy than patients with a significant decrease in tumour cell mass.

Adrenal Cortex Hormones↗

Nonsecretory multiple myeloma. Presenting findings, clinical course and prognosis.

The present report gives information both on the clinical features at presentation and the clinical course of 7 consecutive patients with nonsecretory multiple myeloma. It provides evidence that the nonsecretory variant was closely associated with high tumor cell mass, as determined by severe anemia and/or multiple areas of bone destruction. The marked depression of normal immunoglobulins and the absence of both renal failure and hypercalcemia differentiated nonsecretory from typical myelomatosis. Finally, the survival length of patients with nonsecretory myeloma appeared to be similar to that of comparably staged patients with secretory myeloma.

Actuarial Analysis↗

Meningeal leukemia complicating prolymphocytoid transformation of B-chronic lymphocytic leukemia.

A patient who developed a meningeal leukemia during prolymphocytoid transformation of B-chronic lymphocytic leukemia is described. The central nervous system (CNS) complication occurred after 5 years of relatively benign course. Almost all CNS mononuclear cells showed the typical morphology and immunology of prolymphocytic leukemia cells, whereas a mixture of prolymphocytoid elements and small-sized lymphoid cells was observed in peripheral blood. In this case the more aggressive component was present at diagnosis and showed an uncommonly slow progression allowing the occurrence of the CNS involvement.

B-Lymphocytes↗

Lonidamine in the treatment of chronic lymphoid leukemia.

Blood and/or bone marrow cells from patients with hematological malignancies, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia in blastic phase, acute lymphoid leukemia, acute myeloid leukemia, prolymphocytic leukemia, multiple myeloma and myelofibrosis, were incubated with Lonidamine at different concentrations (50, 100 and 160 micrograms/ml) for 1-2 h. B lymphocytes of CLL had the highest sensitivity to the drug: a decrease of more than 30% in the viable nucleated cells was recorded in 8 out of 10 experiments. Subsequent in vivo studies were performed to investigate the effectiveness of Lonidamine in the treatment of CLL. The drug was administered orally for a period of 7 days to 19 selected patients, both previously treated and untreated, in different stages of the disease. Only 5 patients responded: 2 of them had a significant decrease (greater than 30%) in the lymphocyte count, and the remaining 3 showed an appreciable reduction of the spleen (1 case) and of the lymph node size (2 cases). Generalized myalgia was the most common side effect induced by Lonidamine.

Antineoplastic Agents↗

Membrane phenotype and functional behaviour of T lymphocytes in multiple myeloma: correlation with clinical stages of the disease.

The distribution of T lymphocyte subsets was assessed using monoclonal antibodies (MoAbs) in 44 untreated patients with multiple myeloma (MM) subdivided according to the clinical stage of the disease. A significant reduction (P less than 0.001) of T lymphocytes was observed only in stage II and III patients. The proportion and absolute number of OKT4 positive cells (helper/inducer phenotype) were significantly reduced in all stages of the disease; this quantitative abnormality was more pronounced in advanced disease. While the proportion of OKT8 positive cells (suppressor/cytotoxic phenotype) was increased above normal in all stages, the absolute number (of OKT8 positive cells) was high only in stage I patients; on the contrary in stage II-III patients the total OKT8 count was reduced compared with normal controls. A significantly reduced OKT4/OKT8 ratio was found in both groups of patients (P less than 0.005). Functional studies, carried out on the unfractionated T cells of patients with MM, demonstrated a consistent helper defect in the ability to induce the differentiation of normal B lymphocytes into antibody producing cells in a pokeweed mitogen driven system. However, the removal of OKT8 positive cells produces a significant increase in helper capacity, suggesting that the reduced helper function of T lymphocytes in toto is probably due to excessive suppressor activity. The possible immunoregulatory role of MM T cell disease is discussed.

Antibodies, Monoclonal↗

Functional behaviour and immunological phenotype of circulating B lymphocytes in multiple myeloma. Studies with pokeweed mitogen.

Peripheral blood B lymphocytes, depleted of adherent cells, from 10 patients with multiple myeloma were cultured in the presence of PWM with autologous or donor T lymphocytes. The results show that: (1) co-cultures with allogeneic T lymphocytes produced more plasma cells than those with autologous ones; (2) the kappa/lambda ratio overlapped the values obtained in normal controls, irrespective of the light chain produced by the neoplastic plasma cells and (3) the immunological phenotype of plasma cells obtained from PWM stimulated peripheral B cells (RFA2+, RFA3+, A10+) was clearly different from that one of myelomatous plasma cells (RFA2-, RFA3-, A10+). These data confirm the T cell imbalance already seen in myeloma patients; moreover they show that PWM responsive B cell are functionally normal and phenotypically different from bone marrow myeloma cells. These results support the view that most of the peripheral B lymphocytes, previously identified as monoclonal are in fact normal cells bearing adherent monoclonal Ig molecules.

Antibodies, Monoclonal↗

Hodgkin's disease and subacute cerebellar degeneration. A case report and review of the literature.

Case history of a 20-year old man with Hodgkin's disease, clinical stage I, lymphocytic predominance, complicated by a subacute cerebellar degeneration, which was diagnosed by computed tomography scan. Following local radiotherapy, cerebellar and brain stem symptoms and signs had a complete regression. Two months later, a recurrence of the neurological picture was recorded: polychemotherapy (MOPP) was then administered and after 5 courses the symptoms improved considerably. The association of subacute cerebellar degeneration with Hodgkin's disease is rare: only 10 cases have previously been described. Pathogenesis of cerebellar atrophy complicating tumors is undetermined.

Adult↗

Prognostic value of bone marrow plasma cell infiltration in stage I multiple myeloma.

We analysed for prognosis and response to chemotherapy a series of 48 consecutive stage I myeloma patients who were treated with melphalan and prednisone soon after diagnosis. It was found that the extent of bone marrow plasma cell infiltration had prognostic value, the survival of the patients with more than 50% plasma cells being significantly shorter (P less than 0.005) than that of the patients with less than 50% plasma cells. In the latter group, the observed number of deaths was so small (two cases) as to preclude any further analysis. In contrast, in the former group, a significant relationship between the response to chemotherapy and patients' survival (P less than 0.001) was demonstrated. We conclude that a prospective randomized trial of treatment versus no treatment is warranted in stage I patients who have a high risk of death (i.e. with a high bone marrow plasma cell infiltration) in order to establish whether chemotherapy prolongs the length of survival.

Adult↗