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Biomedical subjects

C Bernasconi

Publications and source records attributed to C Bernasconi.

At least 109 records · Page 6Linked to original sources
PubMed1991

Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

In the chicken, three tenascin variants have been characterized that are generated by alternative splicing of 3 of its 11 fibronectin type III repeats. Using monoclonal antibodies that react with common regions versus extra repeats of tenascin, we could distinguish and separate tenascin variants and investigate their interaction with fibronectin using multiple experimental procedures. Interestingly, in all assays used the smallest tenascin variant bound more strongly to fibronectin than the larger ones. These biochemical data were paralleled by the observation that in chick embryo fibroblast cultures only the smallest form of tenascin could be detected in the fibronectin-rich extracellular matrix network laid down by the cells. Furthermore, each tissue present in adult chicken gizzard contained a distinct set of tenascin variants. Those tissues particularly rich in extracellular matrix, such as the tendon, contained the smallest tenascin only. Intermediate-sized tenascin was present in smooth muscle, whereas the largest form was exclusively detectable underneath the epithelial lining of the villi. Thus it appears that cell type-specific forms of tenascin exist that are appropriate for the functional requirements of the respective extracellular matrices.

Animals↗
PubMed1991

MACOP-B for advanced stage large cell lymphoma (DLCL). More is better? Italian Multiregional Cooperative Study Group (IMCSGL).

A study of the predictive value for CR, DFS and OS of the presenting features was carried out on 180 patients with advanced stage DLCL treated with MACOP-B between June 1986 and March 1989. A multivariate regression analysis identified LDH level, bone marrow involvement and tumor burden as independent risk factors with a 4 year survival rate of 79%, 58% and 28% respectively. Therefore MACOP-B proved to be an adequate treatment for the first two groups of patients but not for the third which requires a more aggressive treatment. A sequential single drug high dose chemotherapy with collection of peripheral blood stem cell program followed by bone marrow harvesting, super-intensive radio-chemotherapy and bone marrow transplant has been activated. Seven patients have been so far enrolled: preliminary results demonstrated the feasibility of the program. A larger number of cases and a longer follow-up is required for assessing the efficacy of this approach.

Adolescent↗
PubMed1991

Burkitt's lymphoma/leukemia: a clinicopathologic study on 24 adult patients.

We have retrospectively analyzed the characteristics of 24 adult patients affected with non-endemic Burkitt's lymphoma (BL) and Burkitt cell acute leukemia (L3 ALL). The median age of the entire group was 29 years with a male preponderance (75%). Median LDH value was 580 mU/mL. Test for HIV-antibodies was carried-out in 16 patients; 5 of them (21%) showed HIV positive. CNS was involved in 25% of patients at diagnosis. In all cases studied for karyotype, the t(8;14) translocation was evident. As to therapy, 5 patients were not evaluable for early death, 12 were given an intensive ALL program, 5 a cyclic chemotherapy and 2 a new protocol alternating high-dose cyclophosphamide, high-dose cytarabine with mitoxantrone and the CHOP regimen. The overall complete remission rate was 42%; among 7 remitters, 4 have relapsed so far within a median time of 6 months. Three of 13 (23%) patients with lymphoma presentation are long remitters and may be cured; all cases had stage II disease and low LDH at diagnosis (less than 250 mU/mL). No patients with Burkitt's leukemia survive. CNS disease (8 cases) and septic shock (6 cases) were the most frequent terminal events. In our experience, the prognosis of advanced stage BL and L3 ALL in adults does remain dismal; the high prevalence of CNS disease and HIV-positivity may have contributed to the poor outcome.

Adult↗
PubMed1990

Mitoxantrone for refractory and relapsed acute leukemia.

Seventy-seven patients with relapsed or refractory acute leukemia and three with acute blastic chronic myeloid leukemia (CML) were treated in an open Phase II study using mitoxantrone 12 mg/m2 intravenously daily X 5 days. Complete remission (CR) was achieved in 32 of 80 (40%), including 23/45 (52%) with relapsed acute nonlymmphocytic leukemia (ANLL), four of 12 (33%) with relapsed acute lymphocytic leukemia ALL, four of 17 (24%) with ANLL refractory to daunorubicin + cytosine arabinoside, and one of three (33%) with refractory ALL. None of the patients with acute blastic CML achieved CR. Median survival time for all patients was 121 days. Median duration of complete response was 303 days with ten of 32 patients in continuing CR for periods varying from 44+ to 1210+ days. Apart from moderately prolonged hematologic suppression toxicity was mild and subjective side effects were tolerable. Mitoxantrone is an active agent in the treatment of acute leukemia and demonstrates incomplete cross resistance with duanorubicin. Mitoxantrone should be considered for first-line therapy in ANLL.

Drug Administration Schedule↗
PubMed1990

Lymphoblastic lymphoma in adult patients: clinicopathological features and response to intensive multiagent chemotherapy analogous to that used in acute lymphoblastic leukemia.

This paper analyzes the clinicopathological features of 31 consecutive adult patients with lymphoblastic lymphoma (LBL) and reports on our experience in treating them with two successive multidrug programs analogous to those used in acute lymphoblastic leukemia (ALL) in adults. Protocol 1 (18 patients) consisted of an intensive four-drug induction therapy (daunorubicin, cyclophosphamide, vincristine, prednisone), CNS prophylaxis (cranial irradiation and intrathecal methotrexate), and continuous maintenance with methotrexate and mercaptopurine for three years, with periodical reinductions with vincristine and prednisone. Protocol 2 (13 patients) included a similar induction regimen (doxorubicin instead of daunorubicin, dexamethasone instead of prednisone), followed by post-remission intensification with alternating courses of non-cross-resistant agents (amsacrine and high dose cytarabine; vincristine, cyclophosphamide and doxorubicin; etoposide and conventional dose cytarabine) given in a cyclical eight-month program. CNS prophylaxis consisted of intrathecal methotrexate and systemic high-dose cytarabine. The patient characteristics of the two therapy groups were comparable. The complete remission (CR) rate for both groups was 77%, with a median overall and relapse-free survival of 18 and 29 months, respectively. The three-year overall survival of complete remitters was 59%. No correlation was found between CR rate and age, mediastinal, or bone marrow involvement. Stage I disease had a significantly higher CR rate (100%) than did stages II-IV (64%). Leukemic evolution occurred in 32% of cases, within a median time of 11 months from diagnosis; meningeal disease developed in six cases (19%); in four of them leukemia was concomitant. No significant differences were found between the two successive treatments for CR rate, survival, CNS relapses or toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Idarubicin (4-demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: a pilot study of the Italian cooperative group GIMEMA.

Because of the reported high sensitivity of acute promyelocytic leukemia to daunorubicin, we treated 27 consecutive, newly diagnosed, acute promyelocytic leukemia (APL) patients with the new anthracycline idarubicin (IDA) as induction therapy. IDA dosage ranged from 0.25 to 0.30 mg/kg/day and the drug was administered as single agent during a single induction course of 6 days. A total of 22/27 patients (81%) achieved complete remission, 4 (15%) died during induction and 1 patient was resistant to IDA. Extrahematological toxicity was acceptable. A total of 13/22 patients having achieved CR are still alive and in first CR after a median follow-up of 12 months. As for the treatment of the coagulopathy present in APL: 17/27 (63%) received tranexamic acid (6 g/daily) in continuous infusion for total of 7 d. None of the patients treated with tranexamic acid experienced thromboembolic complications. In conclusion, this multicentric pilot study confirms the antileukemic potency of IDA and the high sensitivity of APL to anthracycline derivatives.

Adolescent↗
PubMed1990

Therapy of essential thrombocythemia with alpha-interferon: results and prospects.

Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long-term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha-interferon (IFN) exerts a dose-dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non-mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha-IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1-3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9-12 months). Also patients resistant to cytotoxic drugs may respond to alpha-IFN, suggesting a lack of cross-resistance between the two treatment modalities. Side-effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low-dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha-IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.

Humans↗
PubMed1990

Splenectomy after initial therapy with alpha-IFN in patients with hairy-cell leukemia (HCL): a multi-center study by the Italian Cooperative Group for HCL. Preliminary results.

Since December 1987, 115 patients with HCL have been enrolled in a prospective multicenter study to evaluate the role of splenectomy after an induction therapy with alpha interferon. The group of patients was divided into two categories: those younger and those older than 65 years. The schedule of treatment with IFN was, respectively, 1.8 MU/sm/daily and 1.0 MU/daily, 33 patients were treated with r-alpha-2a, 34 with r-alpha-2b, and 25 with alpha-Ly. To date, 92 patients are fully evaluable. The response was assessed every 3 months by bone marrow trephine biopsy. Patients in CR continued IFN therapy for 3 months and, if they were still in CR, could undergo an optional splenectomy. Patients in PR continued therapy for 12 months and subsequently were randomized for splenectomy or observation only. In these preliminary results of an ongoing protocol, CR was obtained in 5 cases (6%), PR in 59 (64%), MR in 25 (27%), NR in 3 (3%). Only 2 of the 5 patients in CR underwent splenectomy and are still in CR. Of the 59 patients in PR, only 15 completed 12 months of therapy. 9 patients in Group A were randomized, 4 were splenectomized and 5 were in the observation arm. All patients were splenectomized safely and no complications occurred. These preliminary results suggest that splenectomy could be effective in consolidating the response obtained with IFN.

Adult↗
PubMed1990

Impact of advanced age on the management of acute nonlymphocytic leukemia: a study of 103 patients.

Treatment and outcome of 103 consecutive patients aged greater than or equal to 60 with de novo acute nonlymphocytic leukemia (ANLL) were reviewed. Twenty-three cases (22%) were not suitable for induction chemotherapy because of very poor presenting general conditions and could receive supportive care alone. The majority of them died within 1 month. Twenty-eight patients (27%) aged greater than or equal to 70 and/or with concurrent nonhematologic disorders underwent mild induction chemotherapy, which produced 3 complete remissions. The median survival for this group was 2 months. Only 52 patients (50%) were considered eligible for conventional induction chemotherapy. For this group, response rate was 34.5%, the median survival was 3.5 months, and median survival for responding patients was 13 months. Only intensive chemotherapy seems capable of substantially improving prognosis for older ANLL patients. This approach, however, is feasible only in a minority of patients, due to a high incidence of life-threatening complications.

Age Factors↗
PubMed1990

Characterization of AIDS-associated tumors in Italy: report of 435 cases of an IVDA-based series.

The Italian Cooperative Group on AIDS-related tumors has collected 435 cases of HIV-associated tumors since December 1986. The following conclusions can be drawn from this IVDA-based series: (1) at least 15% of AIDS cases are associated with tumors; (2) the number of malignant lymphomas (high-grade non-Hodgkin's lymphoma [NHL], Hodgkin's disease [HD] is comparable to that of Kaposi's sarcoma (KS) (188 vs. 198); (3) KS among AIDS patients is less common than in countries where homosexual men are the main group affected by AIDS. However, KS also affects intravenous drug abusers (IVDA) almost exclusively males, with characteristics similar to those observed among homosexual men; (4) HD is associated with an aggressive course; (5) anal and oral primary tumors as well as oral and anal involvement of NHL are very rare; (6) testicular cancers occur in patients mainly with early HIV infection, without adversely affecting the dosage of radiotherapy and chemotherapy; (7) cervical cancer successfully treated with conization suggests that PAP test screening in young IVDA women is warranted; (8) lung cancer occurs in a young age group with rapid progression and death.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Human lymphoblastoid interferon as initial therapy in hairy cell leukaemia: a multicentre study in non-splenectomized patients. Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Cooperative Group for Hairy Cell Leukaemia (ICGHCL), between April 1985 and June 1987, conducted a multicentre study using human lymphoblastoid alpha-interferon as primary therapy as an alternative to splenectomy. Forty-eight evaluable patients with HCL entered the study, 38 of them had splenomegaly, in five patients the spleen was not palpable and five were unfit for surgery because of age and general condition. Daily dose of 3 MU s.c. alpha-IFN was given for 12 weeks, or until a satisfactory and stable response was obtained. Among these 48 patients the response rate after 3 months of therapy was 63%, with seven patients (15%) achieving complete remission and 23 (48%) partial remission; 13 (27%) patients had a minor response. In five patients no response was observed and they died within 2 months of treatment. Five other patients, after an initial response, presented a re-expansion of the disease. Actuarial survival at 30 months was 88.8% for the entire group of 48 patients and 92% for the 38 patients who would normally be treated by splenectomy. Thus, alpha-IFN as primary treatment in HCL offered a reasonable therapy for splenomegalic patients. The timing and validity of splenectomy still remains an open question.

Adult↗
PubMed1989

Interferon alpha-2b as treatment for Philadelphia-negative chronic myeloproliferative disorders with excessive thrombocytosis.

We treated 32 patients with Ph1-negative chronic myeloproliferative disorders (CMD) with excessive thrombocytosis with Interferon alpha-2b (IFN alpha-2b): 26 had essential thrombocythaemia, ET (18 previously untreated, eight pretreated); one thrombocythaemia after treatment for Hodgkin's disease (HD); two thrombocythaemia associated with non-Hodgkin's lymphoma (NHL); three stage II idiopathic myelofibrosis (IM). IFN was given at daily doses of 1-4 x 10(6) IU. Twenty-seven patients (84%) responded, 17 (53%) achieved complete haematologic response after a median time of 12 weeks, and 10 (31%) partial haematologic response. Median platelet levels declined in complete haematologic response patients from 1,190 to 335 x 10(9)/l. Normalization of megakaryocyte (MK) levels was observed in 8/17 complete haematologic response patients treated for 9-12 months, with decreased bone marrow (BM) cellularity. Side effects requiring dose reduction or discontinuation of treatment occurred in 28% of cases with IFN doses of 2 or 4 x 10(6) IU. After 1 year of continuous IFN treatment, responses were maintained with conventional chemotherapy or low-dose IFN. This study demonstrates that IFN has definite therapeutic activity in CMD with excessive thrombocytosis. This biological agent, either alone or in combination with other antineoplastic treatment, may represent a new therapeutic approach for these disorders.

Adult↗
PubMed1989

Mitoxantrone and etoposide: an effective regimen for refractory or relapsed acute myelogenous leukemia.

23 adult patients with refractory or relapsed acute myelogenous leukemia (AML) received salvage chemotherapy with mitoxantrone and etoposide. The regimen consisted of mitoxantrone, 10 mg/m2/d by 30-min infusion, and etoposide 100 mg/m2/d by 30-min infusion, given 12 h apart for 5 consecutive d. Of 23 patients treated, 13 met the criteria for highly refractory disease (6 primary resistant; 4 with early relapse during maintenance; 3 relapsed and refractory to reinduction). 10 patients had relapsed off-therapy more than 6 months after achieving first CR. Overall, 14 patients (61%) achieved a complete remission (CR): 6/13 (46%) with refractory AML, and 8/10 (80%) with relapsed AML. 2 patients had a partial remission, 2 died in aplasia, and 5 were nonresponders. In responding patients, the median time for recovery of granulocyte count was 27 d. The most important nonhematologic side effect was oral mucositis, which was severe in 35% of cases. No signs of cardiac toxicity were observed. The median CR duration was 5 months (range, 2 to 12+ months). The combination of mitoxantrone and etoposide appears a highly effective and relatively well tolerated salvage regimen for refractory and relapsed AML. Its incorporation into first-line induction and consolidation programs for newly diagnosed AML patients should be considered.

Adult↗
PubMed1989

Plasma cell leukemia: a report on 15 patients.

Plasma cell leukemia (PCL) can be considered the leukemic variant of multiple myeloma. The diagnosis is based on hematological features, including a plasmacytosis exceeding 2 x 10(9)/l and any evidence of a clonal plasma cell proliferation. There are two forms of PCL: the primary form occurring in individuals without preceding multiple myeloma, and the secondary form arising as a late manifestation in patients with multiple myeloma. From 1974 to 1988 we diagnosed 8 primary PCL cases out of a total 301 multiple myeloma cases (incidence, 2.6%) and a total of 847 acute leukemia cases (incidence, 0.9%). During the same period we observed in 7 multiple myeloma patients a terminal PCL, for an incidence of PCL in myeloma of 2.3%. Most clinical characteristics were similar in both types of plasma cell leukemia. In particular we found no difference in the average age and in the incidence of bone pain, hepatosplenomegaly, lytic bone lesions. None of our cases showed a clinically relevant lymphadenopathy either as presenting symptom or during the course of the disease. The values for hemoglobin, leukocytes, plasma cells, serum creatinine and calcium did not differ significantly between the two groups of patients. The median survival was 7 months for patients with primary PCL and 1 month for patients with secondary PCL. 5 of the 8 patients with primary PCL obtained a response to conventional myeloma therapy including single alkylating agents, with a duration ranging from 7 to 44 months. Only 1 of the patients with secondary PCL had a partial response after combination chemotherapy.

Adult↗
PubMed1989

Acute nonlymphocytic leukemia: evidence of clonogenic cells in peripheral blood in early complete remission.

We describe a patient with acute nonlymphocytic leukemia in whom chromosomal analysis showed a 8,21(q22;q22) translocation and who entered complete remission after one course of chemotherapy. During the post-chemotherapy aplastic phase blood-derived hemopoietic circulating stem cells were collected by continuous flow aphereses. Chromosomal analysis on the collected cells and on colonies (CFU-GM grown in agar) showed the same anomaly as was present at diagnosis in about 30% of those analyzed. This confirms the persistence of the malignant clone in the early phase of the clinical remission in acute nonlymphocytic leukemia.

Adult↗