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F Cavalli

Publications and source records attributed to F Cavalli.

At least 19 recordsLinked to original sources
PubMed2008

Treatment of pediatric non-Hodgkin lymphomas in a country with limited resources: results of the first national protocol in Nicaragua.

We report the results of a protocol for the diagnosis and treatment of pediatric non-Hodgkin lymphomas (NHL) conducted in Nicaragua in the context of an international collaborative program. Fifty-three children with NHL treated between 1996 and 2003 were retrospectively evaluated. Therapy was designed based on local drug availability and affordability with dose and schedule adaptations for Burkitt and lymphoblastic lymphomas. With a median follow-up of 3 years, the projected 9-year overall survival was 63% and event-free survival 53%. The treatment was efficacious, feasible, and well tolerated in spite of the local socio-economical conditions.

Adolescent↗
PubMed2006

Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws.

OBJECTIVES: It is important to recognize osteonecrosis of the jaws in patients treated with bisphosphonates because an early diagnosis can make a significant difference to the outcome of the disease. The aim of this study is to describe the radiological features of bisphosphonate osteonecrosis (BON) in order to aid its prompt recognition. METHODS: A conventional radiograph, a computed tomograph (CT), a magnetic resonance image (MRI) and a 99Tc(m)-MDP 3-phase bone scan were carried out for 11 patients with BON. The main imaging findings of osteonecrosis are described. RESULTS: Conventional radiography and CT displayed osteolytic lesions with the involvement of cortical bone. MRI demonstrated the characteristic features of osteonecrosis and the oedema of soft tissues. Both CT and MRI were very useful in defining the extent of the lesions. 99Tc(m)-MDP three-phase bone scan was the most sensitive tool to detect the osteonecrosis at an early stage. CONCLUSIONS: 99Tc(m)-MDP three-phase bone scans who could be used as a screening test to detect subclinical osteonecrosis in patients who have received bisphosphonates. CT scans and MRI are useful in defining the features and extent of osteolytic lesions.

Aged↗
PubMed2005

In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas.

BACKGROUND: Mantle cell lymphoma (MCL) has the worst prognosis of all B-cell lymphomas and has poor response to conventional therapy. It is characterized by the presence of a chromosomal translocation t(11:14) (q13;q32) which results in deregulated cyclin D1 expression. Since defects in cell cycle regulation and apoptosis are primary events in MCL, small-molecule inhibitors of cdks-cyclins may play an important role in the therapy of this disorder. CYC202 (Seliciclib, R-roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective inhibitor of the cdk2-cyclin E as well as cdk7-cyclin H and cdk9-cyclin T. MATERIALS AND METHODS: The activity of CYC202 was tested in four human MCL cell lines: REC, Granta-519, JeKo-1 and NCEB-1. The effect of CYC202 on the cell cycle and on apoptosis-, cell-cycle- and transcription-regulation-related proteins was assessed. RESULTS: The IC50 was 25 microM for REC, Granta-519 and JeKo-1 cells and 50 microM for NCEB-1 cells. CYC202 caused an accumulation of cells in the G2-M phase of the cell cycle and apoptosis. CYC202 caused down-regulation of cyclin D1 and Mcl-1 protein levels, possibly because of the inhibition of transcription elongation. CONCLUSIONS: Our data suggest that CYC202 is an active agent in MCL. The concomitant decrease of the phosphorylated and total forms of RNA polymerase II suggests that this could be the main mechanism mediating the biological effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent in this lymphoma subtype.

Antineoplastic Agents↗
PubMed2004

Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma.

BACKGROUND: Optimal therapeutic management of intravascular lymphoma (IVL) lacks precise guidelines. PATIENTS AND METHODS: The clinico-pathological features of 38 HIV-negative patients with IVL were reviewed to define efficacy of chemotherapy in these malignancies. Clinical characteristics of 22 patients treated with chemotherapy and of 16 untreated patients were compared in order to understand better the impact and causes of potential patient selection. RESULTS: Median age was 70 years (range 34-90), with a male/female ratio of 0.9; 23 (61%) patients had Eastern Cooperative Oncology Group performance status (ECOG-PS) > 1; 21 (55%) had systemic symptoms. Cutaneous lesions and anemia were significantly more common among patients treated with chemotherapy; central nervous system (CNS) and renal involvement were significantly more common among untreated patients. Chemotherapy was associated with a response rate of 59% and a 3-year overall survival of 33 +/- 11%. Five of six patients with CNS involvement received chemotherapy: four of them died early; only one patient, treated with adriamycin, cyclophosphamide, vincristine, methotrexate, bleomycin and prednisolone (MACOP-B) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), was alive at 19 months. High-dose chemotherapy supported by ASCT was indicated at diagnosis in another patient (43 years of age, stage I), who was alive at 71 months, and at relapse after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in two patients who died early after transplantation. PS < or = 1, disease limited to the skin, stage I, and use of chemotherapy were independently associated with better outcome. CONCLUSIONS: Anthracycline-based chemotherapy is the standard treatment for IVL. However, survival is disappointing, with a relevant impact of diagnostic delay and lethal complications. More intensive combinations, containing drugs with higher CNS bioavailability, are needed in cases with brain involvement, and the role of high-dose chemotherapy supported by ASCT should be further investigated in younger patients with unfavorable features.

Adult↗
PubMed2004

ChlVPP/ABVVP, a first line 'hybrid' combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysis.

We retrospectively analysed toxicities and clinical results of 61 Hodgkin's lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III-IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6-8 cycles. Involved field radiotherapy (IFRT) (30-35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow-up of 60 months, 5-year overall survival, relapse- and event-free survival were 78.8% (95% CI 68.2-91.1%), 81% (95% CI 70.6-92.2%) and 71.9% (95% CI 68.2-82.2%) respectively. Grades 3-4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non-haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non-haematological toxicity. Long-term results of the ongoing randomized trial, comparing ABVD versus high-dose intensity weekly regimens will be useful to confirm our results.

Adolescent↗
PubMed2003

Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group.

PURPOSE: To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). PATIENTS AND METHODS: A retrospective international survey of 373 patients with primary testicular DLCL. RESULTS: Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. CONCLUSION: Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.

Adult↗
PubMed2003

ACOD, a modified CHOP regimen for elderly patients with aggressive non-Hodgkin's lymphoma.

The aim of this study is to verify the feasibility and the clinical activity of a new CHOP-like schedule (ACOD) with a fractionated days 1 and 8 administration in elderly patients. This regimen was chosen in the attempt to allow a sufficient dose intensity (DI) of each drug with better compliance. Fifty-two patients, (74 years, median age), with diffuse large B cell non-Hodgkin's lymphoma were retrospectively evaluated. Patients received ADM 25 mg/sqm, CTX 500 mg/sqm, VCR 1.2 mg/sqm (max 2 mg intravenously) days 1 and 8 and PDN 50 mg orally, days 1-8. Results showed that 54% of patients reached a complete remission, 21% a partial remission with an overall response rate of 75%. Two-thirds of the patients received at least 70% of the planned dose of cyclophosphamide and doxorubicin and 50% of vincristine and prednisone. The median duration of follow up was 12.6 months (range 0.7-61.4). The estimated median OS was 15.2 months (95%CI = [11.6, not estimable]); the estimated median PFS was 5.7 months (95%CI = [5.12, not estimable]). After 2 years, the proportion of patients alive was 47% (95%CI = 34-64%) and the proportion of patients free from progression was 39% (95%CI = 27-57%). Grade 3-4 leukopenia was observed in 61% of patients with 11% of febrile neutropenia. In conclusion, the ACOD chemotherapy regimen seems safe and feasible in elderly patients. This schedule allowed a sufficient DI of chemotherapic agents with clinical results very similar to those recorded with the standard CHOP regimen in young adults.

Aged↗
PubMed2003

Efficacy of vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy with involved field radiotherapy in early stage (I-IIA) Hodgkin disease patients.

Vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy (CT) with involved field radiotherapy (IFRT) was first described by the Stanford group as an active regimen in early stage Hodgkin's disease (HD). Here, we report our retrospective experience of a modified VBM schedule + IFRT in a similar group of patients. From 1988, 49 patients with stage I-IIA HD received vinblastine (VBL) 6 mg/m2, bleomycin (BLM) 10 IU/m2, methotrexate (MTX) 30 mg/m2 day 1,8 every four weeks for three cycles; IFRT was delivered four weeks later followed by three additional cycles of VBM with a dose reduction of BLM (6 IU/m2). The regimen was well tolerated, with grade 3-4 neutropenia occurring in 20 patients. No acute or late pulmonary toxicity was recorded in our series. Estimated Freedom from Progression (FFP) and Overall Survival (OS) at five years are 75% (95% CI, 60.1%-92.2%) and 85% (95% CI, 73.6%-98.1%), respectively. In this retrospective analysis, VBM + IFRT treatment with bleomycin dose reduction seems safe and active. Such combination could be considered as first line treatment for early stage HD patients with favorable prognosis and/or not suitable for anthracyclines-containing regimens.

Adolescent↗
PubMed2002

A multicenter study of treatment of primary CNS lymphoma.

OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.

Adolescent↗
PubMed2002

Relevance of intraocular involvement in the management of primary central nervous system lymphomas.

BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are anecdotal. Cases of IOL included in an international multicentre series of 378 immunocompetent patients with primary central nervous system lymphomas (PCNSLs) were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in 170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by chemotherapy in five; one patient was not treated. Chemotherapy included high-dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy. Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was positively correlated to systemic symptoms and meningeal disease. Fifteen patients (71%) achieved an objective response; 16 patients experienced a failure (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less common in patients treated with chemotherapy plus ocular irradiation and was associated with a significantly shorter survival. Seven patients are alive [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of whom were treated with ocular irradiation. The patient with isolated IOL is alive and disease-free at 14 months. OS of the entire series was similar to that of PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually associated with concomitant brain disease and shows a survival similar to that of the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in better control of ocular disease, which seems to be associated with survival. In view of the potential role of ocular irradiation, the use of chemotherapy alone in phase II trials should be critically reconsidered in PCNSL patients with ocular disease.

Adolescent↗
PubMed2002

Treatment of childhood Wilms' tumor without radiotherapy in Nicaragua.

BACKGROUND: Recent trends in therapeutic strategies for Wilms' tumor are based on an attempt to reduce or omit radiotherapy (RT) in a sizable fraction of patients. We report here the clinical and histological features as well as the results obtained in 37 children (23 males, 14 females; median age at diagnosis 3 years, range 0.8-8 years) diagnosed between 1991 and 1996, and treated with chemotherapy (CT) and surgery at La Mascota Hospital, Managua, Nicaragua. PATIENTS AND METHODS: Patients were grouped as follows: those who underwent surgery at diagnosis (group A, n = 4), patients who received preoperative CT because of large tumor size (group B, n = 27), lung metastases (n = 5) or bilateral disease (n = 1) (group C, n = 6). Treatment consisted of vincristine (VCR) and actinomycin-D (ACTD) for 24 weeks in group A, and of VCR, ACTD and adriamycin for 68 weeks in groups B and C. Histology was classified as favorable in 30 patients (81%), unfavorable in six patients (all of group B) and unknown in one. RESULTS: With a median follow-up time of 6.4 years the event-free survival for the whole group was 80.1%+/-6.8 (SE). No event occurred beyond 5 years of diagnosis. CONCLUSIONS: These results suggest that RT does not appear necessary for the majority of patients, and that an excellent surgical approach associated with an intensive CT schedule can control the disease, even in the absence of adequate information on the intra-abdominal tumor extent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Nodal marginal zone B-cell lymphomas may arise from different subsets of marginal zone B lymphocytes.

Nodal marginal zone B-cell lymphoma (MZL) is a rare and not extensively studied entity that accounts for approximately 2% of all non-Hodgkin lymphomas. Complementarity-determining regions 2 and 3 (CDR2, CDR3) of the immunoglobulin heavy-chain variable region (V(H)) genes were amplified by polymerase chain reaction (PCR), cloned, and sequenced in 8 patients with nodal MZL. All showed a potentially functional V(H) rearrangement. The use of V(H) gene families was unbiased and without overrepresentation of any particular V(H) gene or gene family. The presence of somatic V(H) mutations was detected, with a deviation from the closest germ line sequence ranging from 4% to 17% in 6 of 8 patients. In 3 mutations, the replacement-to-silent mutation ratio suggested the presence of an antigen-selected process. Sequencing different subclones of the same cloned PCR products allowed the detection of intraclonal variability in 4 analyzed patients. The observed pattern of V(H) mutations suggested that nodal MZL, formerly deemed a malignancy of memory B cells, may arise from different subsets of marginal zone B cells-the naive B cells that express unmutated V(H) genes-from memory B cells showing somatic mutations without intraclonal variation, and from germinal center B cells defined by their capacity to undergo the somatic hypermutation process. (Blood. 2001;98:781-786)

Adult↗
PubMed2001

Phase I-II study of escalating doses of amifostine combined with high-dose cyclophosphamide.

PURPOSE: To evaluate the feasibility and clinical effects of increasing doses of amifostine administered four times in 1 day with high-dose (HD) cyclophosphamide (CTX). METHODS: A group of 16 patients with a diagnosis of lymphoma were treated with HD-CTX given at a total dose of 7 g/m2 subdivided into four doses, each preceded by increasing doses of amifostine. A group of 12 lymphoma patients previously treated with the same HD-CTX regimen was used as historical controls. RESULTS: The dose of amifostine was escalated in cohorts of three patients each from 4x570 mg/m2 to 4x910 mg/m2 without severe toxic effects. Further patients were treated at the highest dose level. Side effects included a fall in blood pressure (always less than 20% of baseline value), asymptomatic hypocalcemia (from a median value of 2.4 to 1.7 mmol/l) and a decrease in creatinine clearance (from a median value of 102 to 85 ml/min). The parameters of hematotoxicity for patients treated in the study were not significantly different from those of the historical control patients. CONCLUSIONS: Amifostine can be given safely at a dose of 910 mg/m2 four times in 1 day in combination with HD-CTX. With this schedule amifostine did not show a myeloprotective effect.

Adolescent↗
PubMed2001

Sequence of Crm1/exportin 1 mutant alleles reveals critical sites associated with multidrug resistance.

We have previously shown that genes involved in a novel pathway of multidrug resistance (MDR) in the fission yeast Schizosaccharomyces pombe are functionally conserved in human cells (V. Spataro et al. (1997) J Biol Chem 272: 30470-30475). The human homologue of one of these genes, hCRM1, has recently been identified and found to function in nucleocytoplasmic export, a process which controls the subcellular localization and hence activity of a number of key cell cycle regulators and transcription factors. Several mutant alleles of crm1 confer a phenotype of MDR in S. pombe, through the nuclear accumulation of the AP-1 transcription factor Pap1. We therefore sequenced mutations of crm1 in fission yeast in order to guide the search for analogous hCRM1 mutations which could play a role in tumour-drug resistance. Fifteen yeast crm1 mutants were assessed by PCR and DNA sequencing. Four mis-sense mutations were identified in the open reading frame, three of which (G to A transitions at nucleotide positions 385, 895 and 1,288) were capable of conferring the MDR phenotype alone. For three of the four mutations found, the corresponding amino acid changes affect residues which are conserved in the human homologue hCRM1 and lie in highly conserved regions of the CRM1 protein. We analysed the corresponding hCRM1 coding regions by RT-PCR and sequencing in a panel of ten tumour cell lines, including three ovarian lines resistant either to cisplatin or paclitaxel, or to both and one MDR breast cancer cell line with nuclear accumulation of the transcription factor YB-1. No hCRM1 mutations were found in the three cDNA fragments examined in this panel of tumour cell lines. However, the identification of amino acid residues within the CRM1 protein that are critical for the export of the MDR-associated transcription factor Pap1 in fission yeast can guide further analysis of hCRM1 mutations in tumours with a MDR phenotype.

Amino Acid Sequence↗
PubMed2001

Microsatellite instability: application in hereditary non-polyposis colorectal cancer.

Colorectal cancer (CRC) is a significant cause of mortality in Western populations. About 15% of CRC patients report a family history of the disease. Studies on individuals with a genetic predisposition to CRC have been responsible for significant advances in the understanding of this disease. Thus, although developments in molecular biology have been mainly restricted to a minority of individuals with a hereditary background, information obtained from this group may affect the diagnosis and therapy of sporadic CRCs as well. Deficiency in the DNA mismatch repair (MMR) system results in microsatellite instability (MSI). Individuals from hereditary non-polyposis colorectal cancer (HNPCC) kindreds with germline mutations in genes involved in MMR may benefit from clinical screening programs. The higher frequency of MSI in HNPCC than in sporadic tumours suggests that involvement of MMR genes in sporadic adenomas may be uncommon. Consequently

Adult↗