Search PubMed⌕ Search

Biomedical subjects

C Bernasconi

Publications and source records attributed to C Bernasconi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Plateau phase in multiple myeloma: an end-point of conventional-dose chemotherapy.

BACKGROUND AND OBJECTIVE: In multiple myeloma (MM) patients treated with conventional chemotherapy, the attainment and duration of a plateau phase seems to affect survival more than the degree of response to initial treatment. The aims of this study are: 1) to analyze within a cohort of previously untreated MM patients the incidence and the duration of the plateau phase; 2) to correlate it with the presenting features; 3) to assess its impact on survival. DESIGN AND METHODS: A series of 146 consecutive MM patients treated with conventional chemotherapy were evaluated for this study. Of 146 patients, 102 responded (13 achieving complete response, 21 partial response, and 68 minimal response), and 44 showed less than minimal response or a progression. A plateau phase was documented in 115 patients (comprising all responders and 13 non responders. The median plateau phase duration was 21.6 months. The majority of patients received intermittent cycles of chemotherapy (melphalan or interferon) during the plateau phase. In multivariate analysis, lytic lesions, response, and time to the best response (TBR) correlated with the attainment of a plateau, while stage, response as a whole, and TBR showed a significant correlation with the duration. In contrast, the type of response did not correlate with either the attainment or the duration of plateau. To analyze the prognostic impact of presenting features, response to therapy and plateau we used a hierarchical model for survival. The analysis showed that the response to therapy and the duration of plateau significantly affect the survival. INTERPRETATION AND CONCLUSIONS: In multiple myeloma a plateau phase of at least 6 months' duration has a higher impact on survival than the degree of response to conventional chemotherapy so plateau duration could be used as target of therapeutic trials. The best way to maintain the plateau phase remains, however, undefined.

Adult↗
PubMed1998

Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma: correlation with tumor parameters and disease activity.

BACKGROUND: CA 125 is a glycoprotein produced by epithelial ovarian tumors and by mesothelial cells; its levels also have been shown to be elevated in patients with non-Hodgkin's lymphoma (NHL). METHODS: The authors evaluated serum CA 125 levels in patients with NHL to elucidate the frequency of this finding, its relationship with other presenting features, and its potential role as tumor marker. One hundred and fifty-seven patients underwent the first CA 125 assessment at onset, 54 at disease recurrence or progression, and 62 during complete remission (CR). RESULTS: Of the 157 patients evaluated at diagnosis (median CA 125: 26 U/mL; range, 2-1400 U/mL), 63 (40%) had increased CA 125 values. Higher CA 125 levels were associated with advanced disease, aggressive histology, mediastinal and/or abdominal involvement, bulky tumor, high tumor burden, effusions, contiguous extranodal extension, high serum lactate dehydrogenase (LDH) activity, and elevated beta2-microglobulin (beta2-M) levels. Parameters identified by multivariate analysis to be independently associated with high CA 125 were: aggressive histology, mediastinal and/or abdominal disease, bulky tumor, high serum LDH activity and beta2-M serum levels, and the presence of effusion (P = 0.0000; explained variation = 0.64). Of the patients presenting with abnormal CA 125 levels, all those who achieved a CR (35) and 3 of the 6 who achieved a partial response had normalization of CA 125 values by the end of treatment. Conversely, CA 125 remained above normal values in 18 nonresponders. All 62 patients evaluated during CR showed normal CA 125 levels. Among patients first evaluated at disease recurrence or progression, 22 of 54 (41%) showed increased CA 125 levels, which were associated with the same parameters of disease found in patients examined at diagnosis. CONCLUSIONS: High serum CA 125 levels were found to correlate with mediastinal and/or abdominal involvement, high tumor mass, and effusions, reflecting the reaction of mesothelial cells to the tumor. Serum CA 125 is a reliable biologic marker for the staging and restaging of patients with lymphoma. Serial measurements are useful, in conjunction with other markers, for monitoring response to treatment.

Adolescent↗
PubMed1998

Multiple myeloma in younger patients: the role of age as prognostic factor.

The presenting features of 356 previously untreated multiple myeloma (MM) patients grouped according to age were analyzed in order (a) to elucidate the possible differences in initial clinical and laboratory features between patients younger than 50 years and the older ones and (b) to statistically assess the prognostic value of the parameters considered, with particular emphasis on the prognostic impact of age. Patients were divided into two groups: group I included 61 patients aged less than 50, group II comprised 295 patients aged 50 or more. No significant differences were found between the two groups in terms of either clinical or laboratory initial characteristics. The treatments adopted and the response to therapy did not differ in the two groups. The prognostic value of presenting features was evaluated for the whole cohort by univariate and multivariate analysis, considering both the observed survival rates and survival rates corrected for the effect of other independent causes of death, using a Poisson model. In both models, calcium level (RR 2.33), performance status (RR 1.83), and creatinine (RR 1.69) maintained their independent negative prognostic value. In contrast, the impact of age was different in the two models. In fact, patients younger than 50 seem to have a better prognosis when the observed survival rates are considered, but they show an increased risk of death when the model takes into account the expected mortality of the underlying population. In conclusion, this study shows that the younger cohort of MM patients has no distinctive initial characteristics with respect to older patients. In multivariate analysis, creatinine levels, calcemia, and performance status show a relevant negative independent prognostic value. Regarding the prognostic impact of age, survival seems to be better among patients younger than 50 than in older patients when the observed survival rates are considered but is significantly worse when the mortality of the corresponding general population, is taken into account.

Adult↗
PubMed1998

The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy.

Anemia is a frequent complication of multiple myeloma, becoming chronic in patients who are resistant to chemotherapy. This randomized, parallel, controlled multicenter study (71 patients receiving concomitant chemotherapy) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy. Forty patients were treated with subcutaneous epoetin alfa (150 IU/kg per dose, increasing to 300 IU/kg per dose, every 3 weeks) for 6 months, and 31 entered a control group. The epoetin alfa group had a significantly (P < or = 0.001) greater percentage of patients (75% vs. 21%) with increases in hemoglobin levels and/or reduced transfusion requirements. In 44 non pre-transfused patients (20 controls, 24 in the epoetin alfa group), the mean increase in hemoglobin was significantly (P < or = 0.0001) greater in the epoetin alfa group (+2.1 vs. -0.2 g/dl). Increases in hematocrit and red blood cells were also significantly (P < or = 0.0001) greater in epoetin alfa-treated patients, with corresponding reductions in transfusion requirement. In the 27 pre-transfused patients (11 controls, 16 in the epoetin alfa group), there was a trend towards reduced transfusional need in epoetin alfa-treated patients. Thus, in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused.

Aged↗
PubMed1998

A complex translocation (5;7) in a patient with acute nonlymphocytic leukemia evolved from a myelodysplastic syndrome.

Complete or partial monosomy for the long arms of chromosomes 5 or 7 or both is frequently observed in therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia. Sporadic cases have been reported in which partial monosomy is due to unbalanced translocations. The patient described herein carries one such rearrangement. 46,XY,t(1;2) (q32;p23),del(5)(q13),der(7)(5qter-->5q22::7p15-->7 q21:),del(12)(p12), resulting in partial monosomy for the long arms of chromosomes 5 and 7 and in partial monosomy for the short arm of chromosome 7.

Chromosome Deletion↗
PubMed1998

Fournier's gangrene: a clinical presentation of necrotizing fasciitis after bone marrow transplantation.

Three patients with ANLL developed Fournier's gangrene as an early complication after allo-BMT (two cases) and auto-BMT (one case); two patients were in first CR, the third had resistant disease. Patients developed fever, perineal pain, swelling and blistering of the genital area. Pseudomonas aeruginosa was isolated from the lesions and patients received systemic antibiotic therapy, surgical debridement and medication with potassium permanganate solution. Two patients made a complete recovery although one died of sepsis. The third had progressive involvement of the abdominal wall and later died of leukemia. Early diagnosis of this disorder and prompt initiation of appropriate therapy can prevent progression of this acute necrotizing infection.

Abdominal Muscles↗
PubMed1998

Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS.

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.

Acute Disease↗
PubMed1998

Immunohistochemical detection of porcine epidemic diarrhea virus compared to other methods.

An immunohistochemistry method using formalin-fixed tissues, a direct immunofluorescence method using cryostat sections, an enzyme-linked immunosorbent assay (ELISA), and a PCR method were compared for diagnosis in a litter of weaned pigs that had been experimentally inoculated with wild-type porcine epidemic diarrhea virus (PEDV) and killed between 6 and 60 h after onset of diarrhea. The immunohistochemistry method proved to be as reliable as direct immunofluorescence for diagnosis of PEDV in tissues collected postmortem. The good reliability of ELISA for investigating clinical samples was confirmed, whereas the PCR method used was ineffective.

Animals↗
PubMed1998

Effects of infusions of ACTH in the chronically catheterized pregnant ewe and her fetus.

To study the effects of elevated maternal levels of adrenocorticotropic hormone (ACTH) on the fetus, nine chronically catheterized pregnant ewes (132 +/- 0.9 days of gestation) were infused intravenously for 3 days with Synacthen (5 micrograms.kg-1.day-1). Four ewes were given 0.15 M saline intravenously over the same period. ACTH induced hypertension in the ewe. Mean arterial pressure (MAP) increased from 101 +/- 4.4 to 114 +/- 3.9 mmHg at 48 h (P < 0.05); cardiac output increased from 8.6 +/- 0.5 to 10.4 +/- 1.0 l/min after 24 h (P < 0.05). Within 2-4 h, maternal cortisol levels increased from 24.6 +/- 6.3 to 287 +/- 30 nM (P < 0.05) and remained high. Fetal plasma cortisol levels increased from 20 +/- 4.5 to 60 +/- 4.5 nM (P < 0.05) within 2-4 h and then increased further. Fetal MAP was increased at 24 h. There was no effect on fetal blood gases or pH. Ewes became hyperglycemic and lactacidemic by 24 h (P < 0.05), and the fetuses were also hyperglycemic and lactacidemic (P < 0.05) at this time. There were no changes in fetuses carried by saline-infused ewes. Both ewes and fetuses had raised plasma osmolalities and, since hematocrit fell, retained fluid. Ewes became hypokalemic; the fetuses did not, but there was an increase in fetal K excretion. Thus ACTH-induced hypertension in the ewe had minimal effects on fetal MAP, fetal blood gas status, and pH. The fetus, however, did show many of the other effects of maternal glucocorticoid and mineralocorticoid excess, partly because its cortisol levels were increased but also as a consequence of metabolic and endocrine changes in the ewe.

Adrenocorticotropic Hormone↗
PubMed1998

Efficacy of a combination of idarubicin, etoposide and intermediate-dose cytosine arabinoside as salvage therapy in relapsing or resistant unfavorable lymphoma.

BACKGROUND AND OBJECTIVE: Idarubicin, an anthracycline analogue, is active in non-Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone-based regimens. DESIGN AND METHODS: Thirty patients with relapsing or resistant unfavorable lymphoma received a combination of idarubicin 12 mg/m2 i.v. on day 1, etoposide 60 mg/m2 i.v. every 12 hours for 3 days, and Ara-C 1 g/m2 i.v. every 12 hours for 3 days (3-hour infusion). Median age was 39 years (range: 22-60). All patients had been given prior doxorubicin or novantrone; 54% of them had received 2 or more chemotherapy regimens; 67% of total were in clinical relapse (30% in their second relapse), and 23% had resistant disease. RESULTS: The overall response rate to IVA was 60% (18 of 30 patients). Complete remission rate was 20% (6 of 30) in the whole group, 45% (5 of 11) among patients in their first relapse. Remission median duration was 9 months (range: 1-18), with a 3-year relapse-free and overall survival of 20% and 15%, respectively. Severe neutropenia occurred in 13 patients (43%) and severe thrombocytopenia in 11 patients (37%), with a median duration of 9 and 13 days, respectively. No cardiac toxicity developed; sepsis during neutropenia was documented in four instances and two patients (7%) died of therapy-related events (septic shock). INTERPRETATION AND CONCLUSIONS: Idarubicin combined with etoposide and intermediate-dose cytarabine proved to be an active salvage therapy in unfavorable lymphoma given prior doxorubicin or novantrone; the best results were obtained among patients in their first relapse, with low tumor burden.

Adult↗
PubMed1998

Management of acute promyelocytic leukemia relapse in the ATRA era.

BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.

Adolescent↗
PubMed1998

The risk of acute leukemia in patients treated for Hodgkin's disease is significantly higher aft [see bined modality programs than after chemotherapy alone and is correlated with the extent of radiotherapy and type and duration of chemotherapy: a case-control study.

BACKGROUND AND OBJECTIVE: Patients treated for Hodgkin's disease have an increased risk of developing subsequent acute leukemia. This co-operative study was conducted to assess the relative risk associated with several candidate factors including age, splenectomy, combined modality therapy and cumulative drug dose including alkylating agents and nitrosurea derivatives. DESIGN AND METHODS: This study evaluated the risk of acute leukemia according to pretreatment variables and therapy modalities among 1659 patients treated for Hodgkin's disease and followed for a median time of 10 years. Both case-control and actuarial risk studies were performed. Median age was 34 years (range: 12-83); 53% of patients were splenectomized. As to the overall therapy, 348 patients (21%) were given radiotherapy (RT) alone, 375 (23%) chemotherapy (CT) alone (including MOPP, MOPP + ABVD or MOPP + ABVD + lomustine); 936 (56%) received both CT and RT, either as primary or salvage treatment. RESULTS: The overall 15-year actuarial risk of leukemia was 4.2%; the hazard function curve showed two peaks of risk at the 3th and the 8th year from the initiation of therapy and no leukemia beyond the 12th year of follow-up. Risk of leukemia was 0.3% after RT alone, 2.8% after CT alone (2.2% after MOPP; 4.4% after MOPP + ABVD + lomustine), and 5.4% in patients given combined modality therapy (10.2% for RT + MOPP; 15.6% for RT + MOPP + lomustine). No leukemia occurred after ABVD alone and the risk was low (0.6%) when neither mechlorethamine nor lomustine were utilized. Patients who had received extended radiotherapy including abdomen and pelvis in addition to MOPP showed a significantly higher risk of leukemia compared to those given limited RT + MOPP (P = 0.01). Case-control analysis indicated advanced stage, type and duration (> 8 months) of CT and extension of RT as significant risk factors for leukemia. Compared to RT alone, the odds ratio was 5.9 after MOPP + extended RT, and 8 when a lomustine-containing regimen was used, as well. Neither age nor splenectomy were independent risk factors for leukemia; splenectomy was influential only when patients had been given MOPP chemotherapy, as well. INTERPRETATIONS AND CONCLUSIONS: Both case-control and actuarial analyses indicated that: a) combined modality therapy with MOPP and extensive RT (including abdomen and pelvis), and the use of lomustine added to the leukemogenic risk of MOPP alone; b) programs without mechlorethamine, procarbazine and lomustine were almost devoid of leukemogenic risk.

Abdomen↗
PubMed1998

[Assessment of clinical competence of medical school graduates in Italy with standardized patients. The opinion of the examinees].

An international collaborative project for the evaluation of clinical competence at the end of the Medical School curriculum using the ECFMG-CSA (Educational Commission for Foreign Medical Graduates--Clinical Skills Assessment) prototype was started in Italy in April 1996. Faculty representatives from Italian Medical Schools and experts from the ECFMG in Philadelphia participated in the Project. The CSA consists of integrated clinical encounters with 10 standardized patients during which the examinee is asked to obtain a focused history, perform a relevant physical examination and communicate initial diagnoses and management plan to the Standardized Patient (SP). The SP then completes checklists that are scored by Faculty members. The project was concluded in Spring 1998 and a total of 173 new graduates were examined. The data elaborated by the primary site in Chieti University will be available in the Fall 1998 by the ECFMG in Philadelphia. This preliminary communication reports the opinions of the examinees on the ECFMG-CSA, contained in the questionnaires administered after the test. Most of the examinees considered this new methodology as a valid tool for the assessment of clinical competence, especially history-taking and interpersonal skills and stated that the SP simulations were realistic. The 72% of examinees indicated that the Medical School curriculum does not adequately prepare for the CSA examination. Lastly, 68% was in favour of including the SP in the Medical Licensing Examination.

Clinical Competence↗
PubMed1997

Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups.

Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

Adolescent↗
PubMed1997

Thrombotic events are not exclusive to the remission induction period in patients with acute lymphoblastic leukemia: a report of two cases of cerebral sinus thrombosis.

It is well established that in acute lymphoblastic leukemia (ALL) patients L-asparaginase (L-Ase) provokes thrombotic events reducing coagulation inhibitors in both adults and children. A tight correlation between thrombotic and hemorrhagic complications and ALL has also been hypothesized because of the high incidence of disseminated intravascular coagulation (DIC) found during the early period of chemotherapeutic treatment apart from L-Ase. All the authors reporting on this subject, however, consider the remission induction phase of treatment the most risky, if not exclusive, for the development of a thrombotic event, in particular if it includes the administration of L-Ase. We report here two cases of ALL patients who experienced a cerebral sinus thrombosis in a later phase of treatment, demonstrating that the thrombotic risk is surely exacerbated by chemotherapy but is not exclusive to the remission induction period.

Adult↗