PubMed Health⌕ Search

Biomedical subjects

L Ridolfi

Publications and source records attributed to L Ridolfi.

32 records · Page 2Linked to original sources
PubMed1996

[Toxicity of high dose methotrexate repeated infusions in children treated for acute lymphoblastic leukemia and osteosarcoma].

We evaluated and compared hematologic, hepatic and renal cumulative toxicity of high dose methotrexate (HDMTX) repeated courses in two groups of pediatric patients: 22 patients affected by "non B" acute lymphoblastic leukemia (ALL) treated, in consolidation phase, with four courses of HDMTX 5 g/mq given intravenously over 24 hours infusion (for a total of 88 courses) according to the Italian Cooperative Protocols AIEOP LLA-88; 18 patients affected by non metastatic osteosarcoma of extremities (OST) treated, in preoperative and postoperative phases, with five courses of HDMTX 8 g/mq given intravenously over 6 hours infusion (for a total of 90 courses) according to CNR-NEO 2 protocol. Severe myelosuppression (neutropenia < 500/microliters and/or thrombocytopenia < 25000/microliters) was more frequently observed in ALL (7% of infusions) than in OST (3%). Hepatotoxicity (serum transaminase elevation > 350 IU/l) was significantly more frequent (p < 0.001) in OST (32% of courses) than ALL (6%). Nephrotoxicity was assimilable in the two groups and the elevation of serum creatinine was never higher than 1.9 mg/dl. We did not observe any increase of hematologic, hepatic and renal toxicity following the HDMTX courses repetition.

Antineoplastic Agents↗
PubMedDate not supplied

Two years' experience of acute rejection monitoring of intestinal transplant recipients by real-time PCR assessment of granzyme B and perforin up-regulation: considerations on diagnostic accuracy.

Granzyme B (GrB) and perforin are promising immunological markers to predict acute rejection of transplanted organs. Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up.

Gene Expression Regulation↗
PubMedDate not supplied

Tumor infiltrating lymphocytes and continuous infusion interleukin-2 after metastasectomy in 61 patients with melanoma, colorectal and renal carcinoma.

AIMS AND BACKGROUND: Adoptive immunotherapy with tumor infiltrating lymphocyte (TIL) reinfusion plus continuous interleukin-2 (IL-2) infusion could represent an innovative way of treating immunogenic tumors. This study therefore recruited melanoma, colorectal and renal carcinoma patients whose metastases had been surgically removed. STUDY DESIGN: The treatment was initially given to 22 patients with advanced disease and more recently to 39 disease-free (DF) patients after radical metastasectomy. The latter group was selected in view of a theoretically better lymphocyte/tumor cell ratio and with the aim to improve disease-free and overall survival (DFS-OS) in very high risk patients. The starting IL-2 dose was 12 MIU/day (West's schedule); doses were modulated on the bases of toxicity parameters. Even though patients received different total amounts of IL-2, all of them completed the treatment. RESULTS: The treatment was offered to 22 advanced-stage cancer patients (12 melanomas, 9 colorectal carcinomas, 1 kidney carcinoma). Few and short stabilizations were observed with a median survival of 12 months (range, 3-29). Subsequently, another 39 patients were treated in an adjuvant setting after radical metastasectomy (18 melanomas, 19 colorectal carcinomas, 2 kidney cancers). Eleven out of 17 DF melanoma patients (64.7%) are still free of disease after a median of 37+ months (range, 5+ - 69+). In the group of DF colorectal cancer patients eight (44.4%) are still DF after a median of 21+ months (range, 7+ - 67+ months). One of the two patients with kidney cancer is still DF after 28+ months. Two patients (1 melanoma and 1 colorectal cancer) had just been treated and were therefore not evaluable. Severe toxicity occurred in three cases but was rapidly resolved. There was a great diversity in IL-2 doses administered; comparison of the total IL-2 dose administered between the patients who are still DF and those who progressed revealed no difference between the two groups of colorectal cancer patients, whereas melanoma patients who progressed received an average IL-2 dose of 6.5 MIU/day versus 15.8 MIU/day in DF patients. No differences were observed in any of the groups between the number of TILs reinfused and clinical response. CONCLUSIONS: The study is still ongoing; it has been decided to focus on DF melanoma patients after radical metastasectomy, for whom the data seem to be encouraging. Further endpoints of the study are the role of IL-2 dosage in the adjuvant setting, and the possibility to make correlations between biological parameters and clinical results.

Adult↗
PubMedDate not supplied

[Liver transplantation from elderly donors].

This retrospective, case-controlled study compared the outcome of 17 OLTs (group A) using livers donated by subjects over 70 years of age with 17 OLTs (group B) with livers from donors under 40. Clinical data were used form the period 1996-1998. The following variables were considered in the analysis: donor clinical and laboratory parameters, cold ischemic periods, intra-operative blood and plasma replacement, 30-day mortality rate, incidence of primary graft dysfunction, acute rejection and arterial complication and long term survival. The main post-operative parameters were also included. Liver biopsy, performed in 9/17 of group A, revealed minimal steatosis. There were 2 post-operative deaths in group A and 1 in group B (p = NS). Two arterial complications were observed in group A (p = NS) and only one patient required retransplantation (p = NS). The only other difference found among clinical variables was the amount of total bilirubin at post-operative days 8 and 10, aPTT at days 6 and 13 and albumin at days 5 and 6. A two-year follow-up showed survival rates to be 88.2% and 94.1% for groups A and B, respectively (p = NS). Candidates over 70 years of age should be excluded as liver donors. In such cases, greater care needs to be placed on pathological vascular conditions related to advanced stage atherosclerosis such as calcified plaques on the hepatic artery, a possible factor in severe postoperative complications.

Adult↗
PubMedDate not supplied

[Combined treatment of inoperable liver metastases from colorectal cancer].

AIMS: Liver resection improves survival in selected patients with colorectal liver metastases. However, the majority of patients with colorectal liver metastases have an inoperable oncological disease. The aim is to investigate whether intra-arterial infusion of chemotherapy, improves response to treatment and may convert a selected group of patients with irresectable liver metastases into an operable state. MATERIALS AND METHODS: Thirty-sex patients (pts) with inoperable hepatic metastases from colorectal cancer were treated with intra-arterial chemotherapy, by angiographic technique. All patients underwent a short 5-FU-based locoregional infusion and the 13 non pretreated patients also received systemic therapy. Evaluation of response was made by CT scan. RESULTS: Total cycles administered angiographically: 132 (range, 1-11). There were no complications associated with the angiographic procedure and no cases of > grade 2 toxicity. One heavily pretreated pt experienced moderate cholangitis and superficial gastric erosion. Thirty-one pts were assessable (20 pretreated and 11 not); there was 1 complete response (CR), 3 partial remissions (PR), 2 stabilizations (SD) among non-pretreated pts (6/11; CR + PR + SD = 55%) and 1 PR and 8 SD among pretreated pts (9/20; PR + SD = 45%). The remaining 16 pts progressed. Four pts became eligible for radical hepatic resection (1 refused surgery and 3 patients were operated on). There was no peri-operative deaths. Median survival of these 3 pts was 24, 28 and 39+ months. CONCLUSIONS: Our data, even if based on a relatively small case series, appear to confirm effective local disease control in this clinical setting. Regional chemotherapy used singly or in combination with systemic chemotherapy may convert a selected group of patients with irresectable liver metastases to an oncological disease that can benefit from surgical treatment.

Adenocarcinoma↗
PubMedDate not supplied

[Adjuvant adoptive immunotherapy in patients with stage III and resected stage IV melanoma: a pilot study].

Adoptive immunotherapy trials with tumor infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) were carried out in the treatment of advanced melanoma with a 34% of overall responses (OR). However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (stage III and resected stage IV). In a pilot study, 22 patients (aged 23-72 years) with stage III-IV melanoma who underwent radical metastasectomy were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10(6) IU/m2) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) in the remaining 14 patients were 44% and 37% and 52% and 45% at 2 and 3 years, respectively. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 10(6) vs 86 x 10(6) IU/m2, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. The effects of tumor immunosuppression in lymphocytes inside the tumor (TCR z and e chains, p56lck, FAS and FAS-ligand) confirmed that the potential function of TIL, immunodepressed at the time of metastasectomy, was significantly restored after in vitro, culture with IL-2. Adjuvant adoptive immunotherapy with TIL and IL-2 seems to improve DFS and OS, in comparison with literature data. Further studies are required to determine its role in the adjuvant treatment of patients with high-risk melanoma.

Adult↗
PubMedDate not supplied

Intra-arterial chemotherapy for liver metastases from colorectal cancer.

The aim was to investigate whether intra-arterial infusion of chemotherapy improves response to treatment in unresectable liver metastases from colorectal cancer. We treated 14 patients (pts) with intra-arterial chemotherapy. Arterial catheters were placed via percutaneous access. Treatment schedule was: 5-FU and mitomycin-C on day 1 every 21 days. Six pts also received from day 3 for 5 days, a continuous intra-arterial 24-hr infusion of interleukin-2 (IL-2). We had only one case of toxicity drug-related > grade 2 (neutropenia). We observed 2 partial response (PR) and 5 stable disease (SD). Median time to disease progression (TTP) and median survival (OS) were, respectively 4 and 15 months.

Adult↗