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Biomedical subjects

M Marangolo

Publications and source records attributed to M Marangolo.

At least 19 recordsLinked to original sources
PubMed2006

Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma.

Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I- and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLA-identical siblings. CD4(+) clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-gamma in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferon-gamma after melanoma stimulation. No CD4(+) clones responded to stimulation with recipient haemopoietic cells. The majority of CD8(+) clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4(+) clone was determined to be an HLA-DR11-restricted MAGE-3 epitope. Antigenic targets of the remaining clones were not elucidated, but appeared to be restricted through a non-HLA-DR class II molecule. We conclude that the blood of allogeneic HLA-matched sibling donors contains melanoma-reactive lymphocyte precursors directed at tumour-associated antigens. Adoptive immunotherapy with unselected or ex vivo-stimulated donor lymphocytes after allogeneic stem cell transplantation has a rational basis for the treatment of malignant melanoma.

CD4-Positive T-Lymphocytes↗
PubMed2006

A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization.

We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34+ cells obtained after mobilization was 8.4 x 10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34+ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.

Adjuvants, Immunologic↗
PubMed2006

Pemetrexed and malignant pleural mesothelioma.

Malignant Pleural Mesothelioma (MPM) continues to be a challenging problem; because few patients may be treated with radical surgery and conventional chemotherapy have achieved very dismal results. Pemetrexed is a new drug with multitarget antifolate activity which seems to be particularly active in many solid tumors and also in MPM. The principal clinical experiences of pemetrexed alone or in combination with other compounds, chiefly platinum and its derivative, are reported. The Italian study on 1114 cases of MPM treated over 30 months is discussed and the definitive results will be available after a complete external review of all responsive patients.

Antimetabolites, Antineoplastic↗
PubMed2005

A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.

BACKGROUND: Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy. PATIENTS AND METHODS: Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B). RESULTS: Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04). CONCLUSIONS: The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.

Adolescent↗
PubMed2005

FDG-PET in the management of germ cell tumor.

Germ cell tumor is the most common malignancy in young men. The cure rate of these patients has tremendously increased in the cisplatin era, and recent results have indicated that the management of patients with GCT is still improving. The use of FDG-PET in the management of patients with GCT has been recently investigated. This report attempts to comprehensively review new advances and delineate the potential applications of FDG-PET in GCT.

Adult↗
PubMed2005

Locally advanced ovarian carcinoid.

Primary carcinoid tumor of the ovary is an extremely rare neoplasm, accounting for less than 0.1 % of all ovarian neoplasms. We report a case of a 79-year-old woman with locally advanced ovarian carcinoid presenting as acute abdomen. At laparotomy, a large mass appeared in the pelvis, with maximum size of 18 cm, growing from the left ovary with infiltration of the left Fallopian tube and compression of the small bowel and the sigmoid tract. A bilateral salpingo-oophorectomy was performed, and the tumor mass was completely removed. Post-operative treatments were not considered due to the absence of data in literature to support adjuvant treatments. Ten years after surgery the patient remains well without evidence of recurrence. Older age should not be considered an absolute contraindication for aggressive surgery, if this represents the best chance of cure. An aggressive cytoreductive surgery remains the best treatment for advanced or locally advanced primary ovarian carcinoid.

Aged↗
PubMed2004

Long-term follow-up of patients with poor prognosis germ cell tumor treated with early high-dose chemotherapy with hematopoietic progenitor cell support: a single-center experience.

The 5-year overall survival rate of patients with germ cell tumor (GCT) with poor prognosis, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification, is 48% after standard-dose chemotherapy and surgery, if necessary. Two recent studies have showed that early high-dose chemotherapy (HDCT) with hematopoietic progenitor cell support (HPCS) may induce a 2-year overall survival rate of 78% in these patients. We report the long-term results of the experience at the Department of Oncology in Ravenna with early HDCT and HPCS in GCT patients with poor prognosis (IGCCCG criteria). Between 1987 and 2002, 18 poor prognosis GCT patients (17 M, one F), median age 24.5 years (range, 17-52), were treated with early HDCT with HPCS. In total, (67%) patients achieved a complete remission and they are continuously disease-free at a median follow-up of 9.2 years (range, 1.7-16.2). One treatment-related death occurred. No patient developed myelodysplasia or a secondary leukemia. This is notably the longest follow-up reported in patients having received HDCT in this setting. No patient achieving a complete remission relapsed. The role of HDCT in poor prognosis GCT will be defined from the ongoing phase III randomized trials.

Adolescent↗
PubMed2004

Innovative therapy for patients with brain metastases: oral treatments.

About 40% of patients with advanced cancer develop metastases in the central nervous system (CNS), mainly from primary tumors of lung, breast and melanoma. In most of cases there are multiple CNS metastases, making surgery or localized radiosurgery not feasible. The current standard of care for these patients is radiation therapy, which can improve neurologic symptoms but does not have any impact on the patient's overall survival. Temozolomide, capecitabine and gefitinib are safe and active in the treatment of CNS metastases from melanoma/recurrent gliomas, breast carcinoma and lung cancer, respectively. New, orally administered drugs hold a great potential for patients with CNS metastases.

Administration, Oral↗
PubMed2004

Gemcitabine versus FLEC regimen given intra-arterially to patients with unresectable pancreatic cancer: a prospective, randomized phase III trial of the Italian Society for Integrated Locoregional Therapy in Oncology.

Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2003

High-dose epirubicin, preceded by dexrazoxane, given in combination with paclitaxel plus filgrastim provides an effective mobilizing regimen to support three courses of high-dose dense chemotherapy in patients with high-risk stage II-IIIA breast cancer.

SUMMARY: We verified the possibility of collecting large amounts of peripheral blood stem cells (PBSCs) to support three courses of adjuvant high-dose dense chemotherapy (HDDC) with high-dose epirubicin, preceded by dexrazoxane, and high-dose paclitaxel, in patients with high-risk breast cancer (>/=9 positive nodes). The mobilizing regimen consisted of high-dose epirubicin 150 mg/m(2), preceded by dexrazoxane 1000 mg/m(2) (day 1), given in combination with paclitaxel 175 mg/m(2) (day 2), plus filgrastim. Of the 25 patients enrolled, one went off study due to a severe hypersensitivity reaction to paclitaxel, another did not undergo leukapheresis due to fever persistent after hematological recovery, while in 23 patients an adequate number of PBSCs was collected by a single leukapheresis. The median number of CD34+, CD34+/CD33-, and CD34+/CD38- cells collected per patient was 17 x 10(6)/kg, 13.4 x 10(6)/kg, and 1.5 x 10(6)/kg, respectively. Neutropenia was the only grade 4 toxicity and lasted a median of 3 days. High-dose epirubicin, preceded by dexrazoxane for the first time used in mobilizing regimen, and paclitaxel plus filgrastim are effective in releasing large amounts of PBSCs, which can then be safely employed to support multiple courses of HDDC.

Adult↗
PubMed2003

Autologous hematopoietic stem cell transplantation for breast cancer in Europe: critical evaluation of data from the European Group for Blood and Marrow Transplantation (EBMT) Registry 1990-1999.

The aim of this study was to identify trends in high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (ASCT) and to assess survival in a large cohort of breast cancer (BC) patients receiving this therapy in Europe from 1990 to 1999. A total of 7471 patients who received HDC with ASCT between January 1, 1990 and December 31, 1999 were reported to the European Group for Blood and Marrow Transplantation Registry. Data required for demographics and survival analysis were available for 2679 patients with high-risk primary BC; 921 patients with inflammatory BC (IBC), and 2295 patients with metastatic disease. The main evaluation parameters were progression-free survival (PFS) and overall survival (OS). Between 1990 and 1998, autotransplants for BC increased 30-fold. Significant trends included use of blood-derived rather than marrow-derived stem cells, increment of reporting centers and decrease of mortality within 100 days from transplantation. The 5-year PFS and OS probabilities were 53 and 68% for high-risk disease and 42 and 53% for IBC, respectively. For metastatic disease 5-year PFS and OS probabilities in the whole cohort were 18 and 27%, respectively, while for women transplanted in complete remission the 5-year PFS was 29%. In conclusion, HDC with ASCT has been increasingly used until 1998 and the 100-day mortality rate has been constantly less than 2% from 1995 to date. The 5-year survival of high-risk BC is related to the number of axillary nodes involved at surgery. Outcome of patients with IBC is encouraging, suggesting the need for randomized trials. Patients with metastatic disease responding to pretransplant chemotherapy and harboring ER+ tumors have a better outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Sexual functions after high-dose chemotherapy in survivors of germ cell tumors.

We investigated the changes in sexual function in male patients with germ cell tumor continuously disease free after one or two courses of high-dose chemotherapy with hematopoietic stem cell support. A questionnaire was mailed to 35 patients, and 30 patients sent it back. Sexuality was considered a problem by 10 patients (33%), but no patients considered sexuality a major problem. Erection was more difficult to achieve in seven patients (23%) and 10 patients (33%) experienced increased difficulty in maintaining an erection. Eight patients (27%) had the experience of less intensive and less frequent orgasm. In all, 13 patients (43%) thought that both the disease and treatment had worsened their sexual capacity, but 20 patients (67%) were satisfied with their sex life. Most of the patients (63%) considered that insufficient information and counselling had been given by their physicians about the sexual sequelae of therapy. However, the amount of information about the disease and treatment was considered good by 77 and 80% of the patients, respectively. This study shows that 27% of patients were not content with their ability to attain sexual satisfaction due to the illness or its treatment. Communication is an important issue and better information tools could lead to improved compliance in these patients.

Adolescent↗
PubMed2003

Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.

Administration, Oral↗