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Biomedical subjects

F Cavalli

Publications and source records attributed to F Cavalli.

At least 55 records · Page 3Linked to original sources
PubMed2000

Morphologic, immunophenotypic and in vitro growth characteristics of blood and bone marrow associated with stem cell mobilisation in patients with lymphoma.

The proportion of CD34+ cells in the bone marrow (BM) is predictive of the size of progenitor cell mobilisation into the blood (PB). To investigate which other PB and BM parameters may be related to mobilisation, we analysed at steady state PB and BM of 23 patients with relapsed or resistant lymphoma before administering high-dose cyclophosphamide and G-CSF Cell morphology, number of CD34+ cells, and growth in clonogenic assay and in long-term cultures (LTC) were determined and then correlated with mobilisation extent (CD34+ and GM-CFC) and quality (growth of harvested cells in LTC). We found that the good mobilising patients (CD34 > 50 x 10(3)/ml, n=10) had several baseline BM characteristics (number of CD34+ MNC, GM-CFC, BFU-E, production of CFCs in LTC) similar to a group of 12 healthy controls, while patients with reduced mobilisation (CD34 < 50 x 10(3)/ml, n=13) had clearly reduced BM progenitors and LTC growth (p< 0.05). In a multivariate analysis including baseline clinical, blood and bone marrow characteristics, the most significant PB and BM factors independently associated with a higher number and/or quality of mobilised cells were a higher number of CD34+ and GM-CFC in the BM and a higher baseline haemoglobin, platelet, and CD34+ blood count. The capacity to release progenitor cells into the circulation is therefore not predicted by the distribution of morphologically distinguishable cells, marginally predicted by the BM content of highly undifferentiated cells (growth in long term culture), while it is proportional to the number of BM progenitors (CD34+, GM-CFC and BFU-E).

Adult↗
PubMed2000

Acute myeloid leukemia in the elderly: results of an individualized approach in two centres.

We retrospectively assessed seventy-four consecutive patients with AML over 65 years of age (median 71; range 65-88) treated with an individualized approach in two specialized cancer centers. Patients were managed according to their performance status (PS) and associated diseases in both institutions. The proportion of patients with poor PS (3-4) was higher in center 1 (37%) than in center 2 (10%) and in center 1 palliative treatment was given more frequently (16/32 patients) than in center 2 (7/42 patients). Fifty-one patients received intensive combination chemotherapy including an anthracycline and ara-C or VP16 (2 patients) and 36 patients received a second intensive course as reinduction or as consolidation treatment after complete remission. Patients not eligible for myelosuppressive chemotherapy were treated with palliative measures (23 patients). With intensive chemotherapy, complete remission (CR) was achieved in 29 of 51 patients (57%), after first (20 patients) or second course (9 patients) and the rate of deaths during induction was 14% (7 patients). The CR rate was lower for patients with performance status >or= 2 (48%) as compared to patients with performance status or= 2) was associated with reduced survival (hazard ratio: 3.29, 95% confidence interval: 1.75-6.17). Overall 2-years and 5-years survival were 20% and 11% for the patients treated intensively. From this study it appears that an individualized approach of treatment with intensive chemotherapy for selected patients offers a substantial CR rate and an improvement in survival. This analysis also suggests that differences in outcome between single institutions can be explained mainly by referral and selection biases

Actuarial Analysis↗
PubMed2000

Prevalence of Helicobacter pylori and hepatitis C virus infections among non-Hodgkin's lymphoma patients in Southern Switzerland.

BACKGROUND AND OBJECTIVE: Several recent studies have reported a high rate of previous hepatitis C virus (HCV) infection in patients with non-Hodgkin's lymphoma (NHL). However, it appears that there are marked geographical differences in the prevalence of HCV among NHL patients. There is further controversy concerning a possible pathogenetic link between HCV and certain histologic lymphoma subtypes, in particular MALT lymphomas, and it has recently been speculated that HCV might be involved in the multistep process of gastric lymphoma genesis, in addition to the well established role of chronic Helicobacter pylori infection. The aim of this study was to investigate the prevalence of HCV and H. pylori infections in patients with B-cell NHL in Southern Switzerland. DESIGN AND METHODS: One hundred and eighty newly diagnosed HIV-negative B-cell NHL patients, consecutively seen at a referral oncology center in Southern Switzerland between 1990 and 1995 were prospectively studied. A microparticle enzyme immunoassay was used to detect antibodies to HCV. Serologic determination of HCV genotype was done by the Murex method. The quantitative detection of IgG anti-H. pylori was performed by the Biorad GAP test. RESULTS: Infection with HCV was detected in 17/180 patients (9.4%; 95% C.I., 6%-15%). This prevalence is significantly higher than that observed in a large survey of 5424 new blood donors from the same area tested in 1992-97 (0.9%; 95% C.I., 0.7-1.2). Neither histologic subtypes nor specific extranodal presentations of NHL were associated with a higher prevalence of HCV. HCV serotype 2 (corresponding to genotypes 2a-c) was the most common. HCV infection was significantly associated with a shorter progression-free survival at both univariate and multivariate analysis. Anti-Helicobacter antibodies were detected in 81/180 patients (45%; 95% C.I., 38%-53%) and H. pylori infection was significantly associated with the development of primary lymphomas of the stomach. INTERPRETATION AND CONCLUSIONS: A high prevalence of HCV infection was detected in NHL lymphoma patients and was associated with a shorter time to lymphoma progression. HCV infection was not correlated with primary gastric presentation or with MALT-type histology. Our findings further support the key role of H.pylori infection in the pathogenesis of primary gastric lymphoma of MALT-type. The possible role of HCV in the pathogenesis of NHL should be further investigated.

Aged↗
PubMed1999

Hodgkin's and Castleman's disease in a patient with systemic mastocytosis.

Systemic mastocytosis is a rare condition characterized clinically by the local consequences of vasoactive peptides released from infiltrating mast cells in the reticuloendothelial tissues. Mast cells originate from the pluripotent bone marrow stem cells; it is therefore not surprising that myeloproliferative and myelodysplastic disorders commonly coexist or terminate the clinical phase of mastocytosis. We report here, to our knowledge, the first case of Hodgkin's and Castleman's disease occurring in a patient with co-existent systemic mastocytosis, which remained unchanged after combination chemotherapy for Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Phase I clinical and pharmacological study of oral methoxymorpholinyl doxorubicin (PNU 152243).

PURPOSE: The methoxymorpholinyl doxorubicin analogue PNU 152243 was brought into clinical studies because of preclinical observations of its non-cross-resistance in mdr tumor cells, dose-limiting neutropenia, lack of cardiotoxicity, and antitumor activity after oral administration. METHODS: PNU 152243 was given orally every 4 weeks to 21 adults with a variety of solid tumors at doses ranging from 59 to 940 microg/m(2). Antiemetic prophylaxis with 5-HT3 antagonists and steroids, given i.v. on day 1 and orally on days 2-8, was required beginning with the dose of 118 microg/m(2). The plasma pharmacokinetics of PNU 152243 were determined by an HPLC method with fluorescence detection. The in vitro myelotoxic effects on granulocyte macrophage-colony forming cells (GM-CFC) of the plasma from 11 patients, obtained 4 and 6 h after treatment at all dose levels, were also assessed. RESULTS: Neutropenia was the main hematologic toxic effect and the maximum tolerated dose (MTD) for myelotoxicity was 940 microg/m(2), with neutropenia grade 3-4 in two of three patients. Dose-dependent nausea and vomiting were dose-limiting and the MTD for gastrointestinal toxicity was fixed at 820 microg/m(2), with grade 4 vomiting in one of two patients. Other frequent toxic effects were diarrhea and fatigue. Peak levels of PNU 152243 were achieved 4 h after dosing. Dose-dependent Cmax and AUCExp, and significant interpatient variability of the main pharmacokinetic parameters were found. Very low levels of the 13-dihydrometabolite PNU 155051 were detected only at the highest doses. The hematotoxicity tests showed a <70% colony growth inhibition with no correlation between the growth inhibition effect and the degree of myelotoxicity in the same patient. Plasma concentrations of PNU 152243 were 1000 times lower than the concentration inhibiting the growth of 70% of colonies. No objective tumor responses were seen. CONCLUSIONS: Owing to the occurrence of severe and prolonged nausea and vomiting, the clinical development of oral PNU 152243 was discontinued. The higher-than-expected neutropenia and its lack of relationship with plasma levels of PNU 152243 and its 13-dihydroderivative PNU 155051 might be related to the formation of potent cytotoxic metabolites present in human plasma at undetectable concentrations and with prolonged half-life, as suggested by hematotoxicity tests performed with plasma from patients in GM-CFC assays.

Administration, Oral↗
PubMed1999

Clinical significance of follicular lymphoma with monocytoid B cells. Non-Hodgkin's Lymphoma Classification Project.

Although follicular lymphoma (FL) is very common in the Western world, very little information is available regarding the frequency and significance of monocytoid B cells (MBC) in FL. We recently completed a clinicopathologic study of 1,378 cases of non-Hodgkin's lymphoma. In this study, a research data sheet was designed to conduct research on several types of lymphomas, one part of which was evaluating the presence of intrafollicular clear cells and extrafollicular MBC in 326 cases diagnosed as FL by one of the pathologists (B.N.N.). For each case diagnosed as FL, the presence of intrafollicular clear cells or extrafollicular MBC was scored as pure FL (no intrafollicular clear cells or extrafollicular MBC), FL with intrafollicular clear cells, FL with less than 5% MBC, and FL with greater than 5% MBC. Of 326 cases classified as FL, 252 (77%) had no intrafollicular clear cells or extrafollicular MBC and therefore were called pure FL. In 36 cases (11%), intrafollicular clear cells were seen, but no extrafollicular MBC. There were no clinical differences between such cases and the 252 cases of pure FL. In eight cases of FL (2%), MBC clusters were rare (<5%). In contrast, 30 cases of FL (9%) had a prominent (>5%) proliferation of extrafollicular MBC; these 30 cases had a significantly shorter failure-free survival (P = .001) and overall survival (P = .04) than the 252 cases of pure FL. The shorter survival of these 30 cases appeared to be independent of the international prognostic index (IPI), stage, and treatment. The FFS of this group remained shorter than that of cases with pure FL when the analysis was restricted to patients treated with Adriamycin-containing regimens and either a favorable (0 to 3) IPI score (P = .001) or advanced stage (III/IV) disease (P = .015). In conclusion, FL with a prominent (>5%) MBC component constitutes a substantial proportion (9%) of FL and has distinctive morphology, and these patients have a significantly shorter survival than those with pure FL.

B-Lymphocytes↗
PubMed1999

Quality of life in postmenopausal patients with breast cancer after failure of tamoxifen: formestane versus megestrol acetate as second-line hormonal treatment. Swiss Group for Clinical Cancer Research (SAKK).

The Swiss Group for Clinical Cancer Research (SAKK) compared efficacy and toxicity of formestane (250 mg intramuscularly (i.m.) every 2 weeks) versus megestrol acetate (MGA; 160 mg orally daily) as second-line treatment in postmenopausal patients with advanced breast cancer and disease progression while on tamoxifen treatment in a randomised trial (Thürlimann B, Castiglione M, Hsu Schmitz SF, et al. Eur J Cancer 1997, 33, 1017-1024). Quality of life (QL) was evaluated as a secondary endpoint (n = 177). Overall, 83% (669/805) of expected QL forms were received, 88% (155/177) at baseline, 88% (402/457) on study treatment, and 65% (112/171) at treatment failure. Patients with no impairment in performance status reported better physical well-being (P = 0.0001), mood (P = 0.0007) and coping (P = 0.03), and less tiredness (P = 0.0001) and appetite/sense of taste disturbance (P = 0.0001) at baseline. After adjustment for baseline, there was no statistically significant difference in QL by treatment. Baseline QL was strongly predictive for QL under treatment but not for time to treatment failure. In conclusion, the question of whether oestrogen deprivation (e.g. formestane) or addition of progesterone (MGA) has a more beneficial impact on QL needs further investigation. The subjective experience of second-line endocrine treatment varies considerably as a consequence of the large variation in the individual course of the disease and has to be judged on an individual basis.

Adaptation, Psychological↗
PubMed1999

START: a European state-of-the-art on-line instrument for clinical oncologists.

START ('State-of-the-Art Oncology in Europe'), a freely available resource on the Internet, is a European 'information base' of current clinical approaches to human tumours. Its aim is to help clinical oncologists make appropriate clinical decisions by providing them with updated information reflecting state-of-the-art cancer treatment as perceived by the European oncology community. It is based upon contributions from authors and internal reviewers from all over Europe as selected by START's editorial board under the supervision of an advisory board and a scientific committee. Close collaborations with the main European cancer societies are ongoing. An external feedback process augments the mechanisms for rendering START a truly European instrument. START is concerned with evidence-based cancer medicine, and the main clinical options are thus codified and their bases indicated in accord with a scale worked out from the perspective of clinical decision-making. Therapeutic options may be 'standard', 'investigational', or 'suitable for individual clinical use' (within the context of a decision made jointly by the patient and the physician). The goal of instruments such as START is to improve the quality of patient care. In addition, START hopes to make contributions to the methodology by which medical research is transformed into clinical decisions.

Decision Making↗
PubMed1999

Microsatellite instability in gastric MALT lymphomas and other associated neoplasms.

BACKGROUND: Microsatellite instability (MSI), caused by a reduced efficacy of the DNA mismatch repair (MMR) machinery, represents a type of genomic instability frequently detected in HNPCC spectrum cancers and in a subset of sporadic carcinomas. The involvement of MSI in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has never been conclusively investigated. In this study, we tested the presence of MSI in tumor samples of patients harboring both MALT lymphomas and other types of malignancies. MATERIALS AND METHODS: We examined 10 microsatellite loci (D3S11, D3S1261, D3S1265, D6S262, D6S193, BAT-26, BAT-25, D17S250, APC, D2S123) out of a total of 34 primary tumors from 14 patients with MALT lymphomas and one or more additional neoplasms. The patients' MSI results were also tested for an association with a positive family history of cancer. RESULTS: MSI, defined by the presence of microsatellite alterations in more than 40% of the examined loci, was scored negative in all tumors studied, and pedigree analysis failed to identify any condition of familial cancer among the patients examined. CONCLUSIONS: The present study suggests that defects in DNA mismatch repair do not contribute significantly to the molecular pathogenesis of MALT lymphomas and associated neoplasms.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1999

Stage-modified international prognostic index effectively predicts clinical outcome of localized primary gastric diffuse large B-cell lymphoma. International Extranodal Lymphoma Study Group (IELSG)

BACKGROUND: The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stage-modified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). PATIENTS AND METHODS: Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. RESULTS: After a median follow-up of 66 months (range 0.6-300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with > or = 3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. CONCLUSIONS: This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.

Adolescent↗
PubMed1999

Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer.

A significant myeloprotective effect of melatonin in mice treated with etoposide, cyclophosphamide or carboplatin has been reported. The present study was designed to evaluate if the same effect could be observed in patients receiving chemotherapy. Twenty previously untreated patients with inoperable lung cancer received two cycles of carboplatin (given at area under the curve 5 by the Calvert formula) on day 1 and etoposide (150 mg m(-2) i.v.) on days 1-3 every 4 weeks. Melatonin 40 mg or placebo (double-blind) was given orally in the evening for 21 consecutive days, starting 2 days before chemotherapy. Patients were randomized to receive melatonin either with the first or the second cycle. Complete blood cell count with differential was done three times per week for 3 weeks. The median age of the cohort was 60 years (range 42-69), 16 patients had non-small cell and four patients small-cell lung cancer, 12 stage III and eight stage IV disease. In a multivariate analysis including age, sex, diagnosis, stage, performance status, doses of carboplatin and etoposide, and concomitant treatment with melatonin or placebo, the haematological parameters--depth and duration of toxicity for haemoglobin, platelets and neutrophils (ANC)--were not significantly different between cycles with/without melatonin. The mean ANC nadir and the mean number of days with ANC < 0.5 x 10(9) l(-1) were 0.5 x 10(9) l(-1) and 2.5 days, respectively, with/without melatonin. We concluded that, in patients with lung cancer, melatonin given orally at a dose of 40 mg per day for 21 days in the evening, does not protect against the myelotoxic effect of carboplatin and etoposide.

Adult↗
PubMed1999

Primary mediastinal large B-cell lymphoma: the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Actuarial Analysis↗
PubMed1999

Defining clinical benefit in postmenopausal patients with breast cancer under second-line endocrine treatment: does quality of life matter?

PURPOSE: In endocrine therapy trials in advanced breast cancer, patients with response (complete response/partial response [CR/PR]) and patients with stable disease for at least 6 months (SD(6m)) have shown similar survival and therefore are often defined as a population with clinical benefit (patients with CR/PR or SD(6m)). We evaluated the impact of response and/or clinical benefit on quality of life (QL) in postmenopausal patients under second-line endocrine treatment after failure of tamoxifen. PATIENTS AND METHODS: One hundred twenty-eight of 177 eligible patients of a randomized trial (Swiss Group for Clinical Cancer Research 20/90) receiving either formestane (250 mg intramuscularly biweekly) or megestrol acetate (160 mg orally daily) were analyzed. The baseline characteristics (with the exception of site of metastases) were balanced among patients with CR/PR, SD(6m), and progressive disease (PD). Patients completed QL indicators at baseline and at 1, 3, 5, 7, 9, and 11 months. Responders were separately compared with nonresponders (patients with SD(6m) or PD) and with patients with SD(6m), and patients with clinical benefit were compared with patients with PD by analysis of covariance with adjustment for baseline scores. RESULTS: Overall, 88% (557 of 634) of expected QL forms were received. In the comparison of responders versus patients with both SD(6m) and PD, responders indicated better physical well-being (P =. 004) and mood (P =.02) at month 3. Compared only with patients with SD(6m), responders showed no significant difference in baseline QL and time to treatment failure (328.5 v 340 days). While under treatment, responders reported significantly better physical well-being (months 3 to 11), mood (months 5 to 11), coping (months 5 to 9), and appetite (months 7 to 11) and less dizziness (month 9) than patients with SD(6m). The changes between baseline and months 5 and 7, respectively, indicated improvement in responders but heterogeneous patterns in patients with SD(6m). CONCLUSION: Although the CR/PR and SD(6m) groups had similar times to treatment failure, patients with CR/PR reported better QL, suggesting more beneficial response to second-line endocrine treatment. Patients' subjective perspective should be taken into account in this mainly palliative setting. Future trials should be designed so that the CR/PR and SD(6m) groups are investigated separately.

Adult↗