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Biomedical subjects

C Bernasconi

Publications and source records attributed to C Bernasconi.

At least 145 records · Page 8Linked to original sources

Human lymphoblastoid interferon for hairy cell leukemia: results from the Italian Cooperative Group.

Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.

Humans↗

Hydroxyurea and 6-mercaptopurine in the treatment of chronic granulocytic leukemia.

From 1975 to 1981, 92 patients with newly diagnosed Ph'-positive chronic granulocytic leukemia entered two consecutive studies. The initial trial (Study I, 1975-1978) tested the efficacy of hydroxyurea (HU) as single agent in 45 consecutive patients. In an effort to improve results obtained with HU alone, from 1978 to 1981, 47 new patients entered a second trial (Study II), which consisted of a continuous treatment with a combination of HU and 6-mercaptopurine (6-MP), at doses adjusted so as to maintain the leukocyte counts between 4 and 12 X 10(9)/L. The aim of this second study was to prolong the duration of chronic phase (CP) by the addition of 6-MP to HU and by a stricter continuous control of the size of the total granulocytic mass (TGM). Both regimens were well tolerated. Median duration of CP was 43 months in Study I and 41 months in Study II. Median survival was 51.5 months and 45 months respectively. These data indicate that neither the addition of 6-MP to HU alone, nor the effort to keep a smaller TGM, play a substantial role in postponement of blastic transformation in CGL.

Adult↗

Myelofibrosis in chronic granulocytic leukaemia: clinicopathologic correlations and prognostic significance.

We performed 221 marrow trephine biopsies in 139 patients with Ph1-positive (Ph1+) chronic granulocytic leukaemia (CGL) in order to assess the incidence, degree and prognostic significance of marrow fibrosis (MF) at various stages of the disease. We also attempted to elucidate the relationship between development of MF and the various clinical and haematological features of CGL. A significant correlation was found between the amount of fibrosis (graded from 0 to 3) and the stage of CGL, indicating that major fibrotic changes are associated with accelerated or blastic disease. Survival studies performed to assess the prognostic significance of the various degrees of MF, showed a progressively worse life-expectancy from grade 0 to grade 3 fibrosis. Multivariate regression analysis indicated Hb level, age, number of marrow megakaryocytes (MKs), time from diagnosis as the features most significantly correlated with the degree of MF. This study demonstrates that the natural history of CGL involves a progressive increase in reticulin deposition towards severe MF, although the rate of this progression varies widely. Monitoring changes of fibrosis with sequential biopsies could give a measure of the rate of progression of the disease and help in prognostic assessment of CGL patients. Our findings also confirm that among marrow features the number of MKs is the cytological variable most significantly correlated with MF.

Adolescent↗

Systemic high-dose ara-C for the treatment of meningeal leukemia in adult acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Considering the good penetration of systemic high-dose ara-C (HDara-C) into the CNS, we used this approach for treating overt meningeal leukemia, either isolated or with concurrent extraneurologic disease, in 15 adults with high-risk acute lymphoblastic leukemia (ALL), one adult with lymphoid blast crisis of chronic granulocytic leukemia (LBC-CGL), and four adults with poor-prognosis non-Hodgkin's lymphoma (NHL). Treatment consisted of ara-C, 3 g/m2 every 12 hours by three-hour infusion for eight doses followed by a second course of four doses on day 21. Remitters received consolidation with monthly courses of HDara-C for four doses. Additional systemic multi-drug reinduction therapy and direct CNS treatment with intrathecal methotrexate (IT MTX) and cranial irradiation (CRT) was administered to the three remitters last treated. Thirteen of 20 patients (65%) achieved complete remission (CR): seven of seven patients with isolated meningeal leukemia and six of 13 patients with concurrent CNS and bone marrow disease. Of the remaining seven patients, five had a complete CSF clearing with persistent marrow disease. In all cases there was prompt resolution of neurologic signs and symptoms. The median duration of CR was 5 months (range 2 to 8 months). The most significant toxicity seen was myelosuppression, which was predictable and manageable. Nonhematologic toxicity was generally acceptable and included moderate nausea and vomiting, diarrhea, drug fever, transient liver dysfunction, and dermatitis. No cases of CNS toxicity occurred. There were no treatment-related deaths. Disease-free survival was limited by marrow relapse, either isolated or with concurrent CNS disease. No instances of isolated meningeal relapse occurred. These results obtained in a poor-risk subset of patients indicate that HDara-C is an effective treatment for the induction of remission in ALL and NHL with meningeal leukemia. Therefore, HDara-C should be considered for inclusion in multiagent consolidation programs for patients at high risk for CNS disease.

Acute Disease↗

Immunoblastic lymphoma: a clinicopathologic study with emphasis on the cases intervening during or following other disorders.

Fifty-eight patients with immunoblastic lymphoma (IBL) were the object of this study. Fifteen of them (26%) developed IBL during or after other diseases, either immunologic or neoplastic, including angio-immunoblastic lymphadenopathy, autoimmune disorders, chronic lymphocytic leukemia, Waldenström's disease, lymphoplasmacytoid lymphoma and Hodgkin's disease (subsequent IBL). The comparison between de novo and subsequent IBL revealed a significantly higher incidence of bone marrow involvement and bulky abdominal disease in the latter group, with a lower response rate to chemotherapy. The favorable primary extranodal disease of Waldeyer's ring exclusively belonged to de novo IBL, whereas the frequency of immunoglobulin abnormalities was higher in the subsequent IBL group (67%). The stage of disease, systemic symptoms at diagnosis and response to therapy were predictive of survival. The overall complete remission (CR) rate in the whole series was 37% and the median overall survival 14 months. Complete remitters have a median survival in excess of 60 months; all relapses occurred within the first 12 months of CR. No CNS relapse terminated the CR, and CNS prophylaxis seems unnecessary in IBL. The analysis of subsequent IBL may provide information on the pathogenesis of non-Hodgkin's lymphomas; the still poor prognosis of IBL deserves new therapeutic attempts to improve on the standard regimens.

Adult↗

Clinicopathologic and immunologic characteristics of non-Hodgkin's lymphomas presenting in the orbit. A report of eight cases.

Of 325 consecutive cases of non-Hodgkin's malignant lymphomas, 8 patients (2.4%) showed orbital presentation. The clinicopathologic and immunologic analysis of the eight patients revealed characteristic biologic features. Despite the apparently isolated orbital presentation, all cases had subclinical systemic disease. Seven of the eight cases exhibited lymphoplasmacytic/cytoid features, with concurrent type II cryoglobulinemia in five of them. In addition, during their clinical course, five patients showed single or multiple subcutaneous nodules with the same histologic and immunologic pattern as the orbital tumor. This study demonstrates that most orbital lymphomas share particular clinicopathologic and immunologic features, suggesting an origin from a B-cell subset with preferential homing to orbital tissues and subcutis.

Aged↗

Terminal deoxynucleotidyl transferase-positive acute leukemias evolving from a myelodysplastic syndrome.

We have analyzed the distribution of terminal deoxynucleotidyl transferase (TdT) in 30 patients with myelodysplastic syndromes (MDS), in connection with morphology, cytochemistry, and cytogenetics. All cases in preleukemic phase were strictly TdT-negative. At variance, 4 (19%) of 21 cases with subsequent leukemia were TdT-positive and showed a pure lymphoid (one case) or a mixed lymphoid-myelomonocytic (three cases) morphology. The TdT enzymatic activity ranged from 2 to 21 U/10(8) cells and the percent of positive cells in the immunofluorescence test ranged from 10 to 80% of total. All cases were Philadelphia chromosome-negative. The clonal origin of MDS from the pluripotent stem cell, capable of originating both a lymphoid and myeloid progeny, is further corroborated.

Acute Disease↗

Low-dose arabinosyl cytosine in acute leukemia after a myelodysplastic syndrome and in elderly leukemia.

Low-dose arabinosyl cytosine (ARA-C) was tested in 15 patients with acute leukemia after a myelodysplastic syndrome (MDS) and in six elderly patients with acute nonlymphoid leukemia (ANLL). The drug was given subcutaneously at 10 mg/m2, every 12 hr for 2 weeks, every 28 days. The overall response rate was 19% (one complete remission, three partial responses), and the median duration of response was 4 months. No particular features at diagnosis were predictive of response. Pancytopenia and marrow hypoplasia occurred after 44 (78%) of 56 courses of therapy and were more severe in nonresponders. Four patients died during the aplasia following ARA-C therapy. Subcutaneous low-dose ARA-C was of limited benefit and bore a noticeable hematologic toxicity.

Acute Disease↗

[Blood viscosity: an original method for the study of low values of the shear rate].

A method for studying blood viscosity at low shear rates (from 4 x 10(-2) to 7 x 10(1) sec-1), i.e. in the shear range in which higher is the influence of shear rate on viscosity, was developed. Blood viscosity is expressed by the two regression coefficients of a power regression, according to the function: eta = a . Db where eta is viscosity. D is the shear rate, a and b are the two regression coefficients, which are independent of the shear rate. We found that the regression power was highly significant in a wide hematocrit range. Practically, this work deals with the possibility of application to the blood of the Ostwald formula for pseudoplastic flow behavior. We found significant correlations between the two regression coefficients and hematocrit and plasma viscosity, so correcting by calculation the two regression coefficients for standard hematocrit and standard plasma viscosity. This method is simple and can easily be automatically driven by a computer.

Blood Viscosity↗

Lymphoblastic lymphoma in adults: a study on 30 patients treated with two different programs according to bone marrow findings.

Thirty adult patients with lymphoblastic lymphoma were treated with two different programs according to bone marrow findings. Bone marrow positive patients were given an ALL-like program: vincristine, daunorubicin, cyclophosphamide and prednisone for induction of remission, CNS prophylaxis, continuous maintenance for three years and monthly reinductions. Bone marrow negative patients were given a conventional lymphoma program with CHOP-Bleo and limited RT on bulky mediastinum without CNS prophylaxis. The CR rate of the whole group was 54% (62% for ALL-treated versus 47% for lymphoma-treated patients; not significantly different), with a median survival for remitters of 28.5 mos. Relapse-free survival of the whole group was 65% at 12 and 25% at 24 mos. Stage IV ALL-treated patients had a median survival of 16.5 versus 10 mos for stage IV lymphoma-treated ones (p = 0.05); the three-years survival was 24 and 10%, respectively. No patients undergoing CNS prophylaxis (ALL-therapy) had neurological complications or late meningeal relapse. The better prognosis of ALL-treated patients, in spite of bone marrow positivity, argues in favor of an ALL-like therapy in all adult lymphoblastic lymphomas, in terms of CR rate, overall survival, and absence of CNS relapse. This therapy must be adopted irrespective of bone marrow findings, and regardless of how localized the lymphoma appears to be.

Adolescent↗

VP 16-213 and cytosine-arabinoside combination chemotherapy for refractory acute lymphoblastic leukemia in adults.

Fifteen adult patients with refractory or relapsing acute lymphoblastic leukemia (ALL) received a 5-day remission induction regimen consisting of VP 16-213 (60 mg/m2 every 12 hr) and cytosine-arabinoside (100 mg/m2 every 12 hr) up to a maximum of three courses. The overall response rate was 60% (9/15), four patients (27%) achieving CR and five (33%) attaining PR. Responders were maintained with monthly courses of the same combination until progressive disease developed. The median duration of response was 4.5 months (2-12+ months). The regimen was relatively well tolerated. The major toxicity was hematologic. Non-hematologic toxicities included mild nausea and vomiting (11/15) and total alopecia (15/15). The results obtained with this combination are encouraging, in view of the poor prognosis associated with refractory or relapsing ALL in adults.

Adolescent↗