Prognostic factors and survival in multiple myeloma. Analysis of 91 cases treated by melphalan and prednisone.
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Biomedical subjects
Publications and source records attributed to M Gobbi.
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Membrane markers of lymphomatous cells were studied in 33 patients with non Hodgkin's lymphoma and correlated with morphological diagnosis according to Rappaport's classification. Nodular lymphomas and the majority of lymphocytic lymphomas showed B cell characteristics, whereas only 6 out of 23 with diffuse pattern were B. None of the histiocytic lymphomas were B, 3 were T, and 4 non T-non B. Mixed lymphocytic/histiocytic lymphomas showed different immunological patterns (B, T, non T-non B, B and T). These results confirm the importance of functional classification, which can clarify the pathogenesis of lymphoma.
Binding of 3H-cortisol (3H-C) and 3H-dexamethasone (3H-DX), a fluorinated glucocorticoid which does not bind to Corticosteroid Binding Globulin (CBG), was investigated in two different target tissues, human breast cancer and human leukemic lymphocytes, using a modified DCC assay method. Maximal binding to cytosol occurred, when increasing concentrations of 3H-C or 3H-DX were incubated in the presence or in the absence of an excess of cold cortisol or dexamethasone, at 0 degrees C for 1 hr or 4 hr, respectively. A 50 sec exposure to DCC was sufficient to separate bound from free labelled steroid. Data presented suggest that two different classes of glucocorticoid exist, which are differently distributed in target tissues, and may be identified on the basis of affinity for the tracer, binding specificity and thermolability.
The clinical and haematological characters and the response to therapy of 32 consecutive patients with acute lymphoblastic leukaemia, aged more than 12 years, were reviewed. All patients were given vincristine (V) and (6-methyl) prednisolone (P) for 6 weeks; daunomycin (D) was added in 9 cases, and cyclophosphamide (C) + D in another 10 cases. 3 patients died during induction. 4 patients failed to achieve remission. 25 patients (78%) achieved complete remission (CR). All of them but one received 'prophylactic' central nervous system (CNS) therapy with cranial irradiation and i.t. methotrexate (MTX) and arabinosyl cytosine. CR was maintained with daily 6-mercaptopurine and weekly MTX. Median duration of CR was of 22 months. 2 patients are currently disease-free and off-therapy, 78 and 53 months after diagnosis, respectively. Blast cell membrane markers were studied in 21 consecutive cases: 3 patients had T-cell leukaemia and 2 patients B-cell leukaemia. Prognostic factors were evaluated basing on the present series of 32 patients, and on further 106 cases reported by others. Age (under and above 40) influenced significantly both the CR rate and the length of survival. In patients aged under 40, a circulating blast cell count higher than 25,000/microliter, or a platelet count lower than 50,000/microliter, negatively affected the survival.
85 patients with previously untreated Hodgkin's disease with stage I, II A and B nodular sclerosis were treated. 31 of them with stage I and II A were submitted to radiotherapy alone. All are alive, but 9 of them (30%) relapsed. On the contrary, 35 patients with stage I and II A, and 19 with stage I, II and IIE B were submitted to radiotherapy followed by three courses of MOPP. All 54 patients are alive and relapse-free. No severe complication related to chemotherapy was observed. The analysis of results suggests that 3 courses of MOPP can significantly (Ip < 0.00025) reduce the relapse rate in patients with stage I and II nodular sclerosis, eligible for radiotherapy, without increasing morbidity.
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Five courses of a combination chemotherapy regimen with methotrexate, cyclophosphamide (Endoxan), and vincristine were given to 64 patients, 37 with lymphocytic lymphoma (LL) and 27 with histocytic lymphoma (HL). Eighteen of the 37 patients with LL (48%) achieved a complete remission (CR); 12 of these 18 patients have been in CR for 20--58 months. Among the complete responders only two died. Twenty-two of the 27 patients with HL (81%) achieved CR and 12 of these patients are still in CR. Ten of the complete responders have been relapse-free for 24--70 months and five have been relapse-free for greater than 60 months. Clinical and hematologic tolerance was such that the interval between each course had to be prolonged in only three of the 64 patients and, with the exception of vincristine, the dosages were not reduced.
Immunological parameters have been evaluated both in vitro and in vivo in 20 Hodgkin's disease patients in continuous not maintained complete remission for at least 3 years. IgG, IgA and IgM levels were within the normal range. Delayed sensitivity, assayed by a battery of recall antigens, was normal too, in the majority of patients. The number of circulating lymphocytes was slightly inferior to normal controls. T cells, evaluated by the rosette E formation, seems to be diminished; on the contrary, B cells, evaluated by the membrane immunofluorescence, were increased in respect to normal controls. The differences are statistically significant. Timidine uptake of PHA stimulated lymphocytes was diminished too. It is concluded that even if these patients' clinical behaviour is like that of normal population, it is possible to find a disorder in vitro parameters, which could be attributable to long lasting effect of the therapy and/or to the persistence of serum factors acting as anti-T cells antibodies.
Acute promyelocytic leukemia (APL) was diagnosed in 13 of 84 adult patients (15.4%) with acute myeloid leukemia (AML) first admitted between 1972 and 1976. All patients had clinical and/or laboratory evidence of defibrination syndrome. Four patients died of cerebral hemorrhage within 2 days of admission. Two patients died of generalized infection on days 7, and 16, respectively, after admission. The remaining 7 patients (54%) underwent complete remission (CR) with daunomycin, arabinosyl cytosine, and adriamycin. All patients received massive platelet transfusion, no heparin, and no granulocyte transfusion. CR was more frequent in patients with a very low blast cell count and a fibrinogen level higher than 100 mg/100 ml. Median survival of these seven CR patients with APL is similar (15 months) to that of CR patients with other types of AML treated at the same institution during the same period.
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Thirty cases originally diagnosed as B-cell lymphomas, either LP immunocytoma, centrocytic (Cc), or centroblastic-centrocytic (Cb/Cc), containing follicular structures of an uncertain nature were critically reviewed using both morphological criteria and immunological techniques. In particular, they were tested by conventional antisera for detection of immunoglobulins in paraffin sections and also, in the 5 cases in which frozen material was available, by a panel of monoclonal antibodies. At the first histological evaluation the cases were divided into two groups. Group A consisted of 12 examples which showed homogeneous features and, because of the neoplastic nature of the follicular structures, could be classified as follicular centroblastic-centrocytic lymphomas with marked plasmacellular differentiation. Group B comprised 18 cases which at onset of disease revealed a mantle-fashion growth around reactive-appearing follicles formed by polytypic germinal centre cells. On closer examination, however, this group appeared heterogeneous: 13 cases displayed cytological and immunological findings consistent with the diagnosis of Cc and usually contained polytypic plasma cells; 5 cases were examples of LP immunocytoma consisting of monotypic elements only. Therefore, the so-called mantle-zone lymphoma does not appear to be an entity.
An analysis of target and effector cell structures involved in the in vitro natural killer (NK)-mediated cytotoxicity has been performed. The degree of surface expression of transferrin receptor (TR) was only in part correlated with that of cell lysis. Moreover, the lysis could not be blocked by treating target cells with two anti-TR monoclonal antibodies. Finally, cell lines poorly affected by NK cells express TR only at the cytoplasmic level. As to the effector cells, the integrity of cytoskeleton components (especially microtubules) was found to be essential for the occurrence of cell lysis. In fact, vinblastine, an anti-microtubule agent, was able to significantly reduce the percentage cell lysis. This effect was not due to a selective depletion in NK cells induced by the drug. It is concluded that the mechanisms underlying NK activity are complex and involve both target and effector cell structures.