Recombinant interferon alfa-2b (Intron A) as post-induction therapy for responding multiple myeloma patients. M84 protocol.
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Biomedical subjects
Publications and source records attributed to M Tribalto.
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To determine whether monoclonal gammopathy of undetermined significance (MGUS) resembles multiple myeloma (MM) with regard to phenotype and functional activity, 16 patients with MGUS and 16 with untreated MM were studied for surface markers and cytotoxic activities phytohemagglutinin-induced cellular cytotoxicity (PHA-ICC), antibody-dependent cellular cytotoxicity, natural killer (NK) activity. Our data showed a consistent immunological similarity between the two diseases. An increase in OKT8+ cells was evident in both patient groups and a significant reduction in the T4/T8 ratio, more pronounced in MM, was observed. Alterations in NK activity or ADCC were not found in MGUS or MM. A significant increase in PHA-ICC was demonstrated in the two diseases. The increase in PHA-ICC observed seems to be attributable to an increased frequency and/or lytic efficiency of PHA-ICC lymphoid effector cells. These data suggest that similar immunological alterations are common to the two diseases. The greater helper/suppressor ratio reduction observed in MM seems to be related to the more severe clonal proliferation in these patients.
Simultaneous evaluation of bone marrow plasma cell thymidine labelling index (LI) and serum beta-2-microglobulin (SB2M) was performed in 146 patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS). Eighty patients had MM on diagnosis, 11 were in relapse and 12 were in remission phase; 43 patients had MGUS. All the evaluated patients had normal renal function with a creatinine level less than 1.4 mg%. Overall there was no direct correlation between LI% and SB2M. LI% best reflected the proliferative capacity of the tumor clone itself being less than or equal to 1% in MGUS and MM in remission, but greater than 2% at relapse of MM. SB2M correlated best with the stage of disease and tumor burden. These two factors therefore have different clinical utility: LI is a useful parameter to detect disease stability (e.g., MGUS) or highly proliferative disease (aggressive MM at diagnosis or early relapse). SB2M remains the best single predictor of patient tumor burden and associated survival duration.
The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.
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The kinetics of bone marrow plasma cells were evaluated by means of in vitro 3(H)thymidine incorporation in 143 patients with monoclonal gammopathies. Fifty-three patients had symptomatic multiple myeloma (MM) at diagnosis, nine were in stable remission, six in unstable remission, and 16 in the relapse phase. Thirty-seven patients were classified has having monoclonal gammopathy of undetermined significance (MGUS) and 22 as smouldering myeloma (SM). A thymidine labelling index (LI%) of greater than 3 at initial diagnosis predicted a very short survival. High LI% values (median 2.8 +/- 1.1) were also seen at relapse. However, the major new finding was that the LI% could be used to discriminate precisely between the SM-MGUS group and the MM patients including stage I disease (P less than 0.0001). Only one patient developed MM during follow up, that being 8 months after the initial diagnosis of SM. During the unmaintained stable remission (plateau) phase a low proliferative activity was also observed (LI% = 0.6 +/- 0.2). Thus the LI% was extremely useful in identification of both poor risk groups with a LI% greater than 3 and stable patients requiring no immediate therapy with a LI% less than 1. The ability to discriminate between MGUS and SM and stage I MM should prove particularly useful clinically.
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The number of blood and bone marrow lymphocytes, the E-rosette forming cells, the Ig-bearing lymphocytes, the serum immunoglobulin levels were evaluated after discontinuation of 36 months of chemotherapy in 15 acute lymphocytic leukemia patients in complete remission. The study provides further information on the immunological rebound during the "off-therapy" period.
Twenty-three refractory and/or relapsing acute non-lymphoid leukemia patients were treated with a combination of methotrexate (MTX) and asparaginase (Aase) slightly modifed from that recently proposed by Capizzi et al. Patients received MTX on day 1, followed by Aase 24 hours later; the two day course was repeated weekly. The starting dose of MTX was 60 mg/m2 and was increased by 50% at each course to maximum toxicity. The dose of Aase was kept constant at 10,000 u/m2. Twelve patients achieved complete remission lasting 3 to 58 weeks, with 8 patients surviving more than 30 weeks. Toxicity has been remarkably mild with the major problem being hypersensitivity to Aase.
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A new case of IgE myeloma is described. Patient G.M., a 60-year-old woman, complained with a 3-months' history of generalized bone pain, weight loss, profound weakness and severe anemia. A bone survey revealed multiple lytic lesions, and a heavy replacement by plasma cells was disclosed in the bone marrow examination of a sternal sample. In addition, an IgE serum M-component and gamma-type Bence Jones proteinuria were identified by immunochemical studies. The disease course was rapid, death occurring within 6 months of clinical onset. A molecular weight of 188,500 daltons was calculated for the purified protein G.M., whereas the molecular weights of its subunits were found to be 72,000 for the epsilon chains and 43,000 for the gamma chain dimers. This case is compared with 15 reported cases of IgE monoclonal gammapathy, an expanding clinical and laboratory spectrum emerging from the review of the literature.
Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).