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M Bendandi

Publications and source records attributed to M Bendandi.

77 records · Page 5Linked to original sources

Apoptosis induction with fludarabine on freshly isolated chronic myeloid leukemia cells.

BACKGROUND: Fludarabine (FLU) is a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Recently, some in vitro reports have showed the effective role of FLU on the activation of apoptosis. MATERIALS AND METHODS: The induction of programmed cell death (apoptosis) by fludarabine (FLU), an adenine nucleoside analogue, alpha-interferon (alpha-IFN), and FLU plus alpha-IFN was evaluated in vitro against freshly isolated, chronic-phase Ph1+ chronic myeloid leukemia (CML). Apoptosis was detected by electrophoresis gel of DNA oligonucleosomal fragments in 8 CML samples. RESULTS: Only FLU and FLU plus alpha-IFN significantly activated apoptosis in all the samples, suggesting selective activity on CML cells. On the other hand, alpha-IFN alone did not activate programmed cell death. CONCLUSIONS: Our data show apoptotic activity for FLU on CML cells. Programmed cell death may be suppressed in cells carrying the bcr-abl transcript, and FLU might remove this resistance in the neoplastic cell cycle. This preliminary report justifies using FLU in pilot clinical trials for chronic phase Ph1+ CML patients.

Antineoplastic Agents↗

Cardiac injury as late toxicity of mediastinal radiation therapy for Hodgkin's disease patients.

BACKGROUND: During the last 20 years Hodgkin's disease (HD) has become one of the most curable neoplasms; in fact, more than 75-80% of patients are expected to achieve long-term relapse-free survival with appropriate therapy. However, overall survival has been affected by intercurrent or treatment-induced diseases such as the increased risk of cardiac toxicity in patients who received mediastinal irradiation. METHODS: The incidence of cardiac abnormalities after mediastinal radiotherapy was assessed in 102 consecutive HD patients who underwent this treatment from January 1970 to December 1980. Basal investigation procedures included electrocardiogram and echocardiography; myocardial perfusion scintigraphy with 201-thallium and coronary arteriography were performed in selected patients. RESULTS: Eleven patients (10.8%) presented cardiac abnormalities, which were asymptomatic in three cases. Eight cases of myocardial ischemia and 3 of constrictive pericarditis were observed. The incidence of late cardiotoxic effects was related to total mediastinal dose and to the irradiation technique. CONCLUSIONS: The increasing duration of follow-up shows that as mediastinal irradiation increases so does the risk of late cardiotoxic side effects. For this reason, a proper treatment strategy should reduce these risk factors through new combined modality protocols and routine evaluation of cardiologic follow-up.

Adolescent↗

FLU-ID (fludarabine and idarubicin) regimen as salvage therapy in pretreated low-grade non-Hodgkin's lymphoma.

Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with promising activity in lymphoproliferative disorders and, in particular, in low-grade non-Hodgkin's lymphoma (LG-NHL). Recently, a few reports have described interesting results using FLU in polychemotherapy regimens. In order to evaluate FLU in combination with other antineoplastic agents, we used a combination of FLU and idarubicin, called the FLU-ID regimen, to treat 10 patients with recurrent LG-NHL. The FLU-ID regimen was as follows: FLU 25 mg/sqm i.v. on days 1 to 3 and idarubicin 12 mg/sqm i.v. on day 1. Of the 10 patients, 2 (20%) achieved complete response (CR), 5 (50%) partial response, and the remaining 3 showed no benefit from the treatment. The 2 CR patients are still in remission after 6 and 8 months, respectively. The median duration of overall survival of all patients was 8 months. The major toxic effects observed were neutropenia (40%) and infections and/or febrile episodes (15%); no fatalities due to drug side effects occurred. These results indicate the efficacy of the FLU-ID regimen in inducing a good remission rate with moderate side effects in recurrent LG-NHL.

Adult↗

Hairy-cell leukemia and alpha-interferon treatment: long-term responders.

BACKGROUND AND OBJECTIVE: In the 1980s alpha-interferon (alpha-IFN) dramatically improved the management of hairy cell leukemia (HCL), producing normalization of hematologic parameters including the disappearance of circulating hairy cells in the majority of treated patients, within 6 months. The quality and durability of the response depended on the duration of alpha-IFN treatment; progression of the disease consistently followed discontinuation of alpha-IFN. In this report, we examine the characteristics of long-term responders from our series of 44 HCL patients treated with alpha-IFN. METHODS: We report follow-up data on 44 HCL patients who underwent alpha-IFN as first-line treatment between 1985 and 1990. The alpha-IFN dose was 3 x 10(6) U daily for 12-15 months, with 20 patients continuing to receive the same dose three times a week as maintenance treatment for an additional 6-12 months. Of the 44 patients, 8 achieved a CR, 28 a PR and 8 a MR, with an overall response rate of 82%. Thirty-eight (86%) of these patients showed disease progression and were retreated with alpha-IFN (2 pts), 2-chlorodeoxyadenosine (35 pts), or pentostatin (1 pt). So far, all 38 patients are alive and in good unmaintained second response, except for two patients who developed a second neoplasm. RESULTS: Six of the 8 first complete responders are alive and have not required further treatment after completing alpha-IFN. These long responders most often (5/6) presented a hairy cell index (HCI) < 0.50 at diagnosis; all 6 registered a significant reduction in bone marrow infiltration (HCI < 0.10) after induction therapy and underwent alpha-IFN maintenance treatment. These three parameters turned out to be statistically significant when the long-term responders were compared with the failure patients subset (p = 0.003 for HCI at diagnosis; p = 0.001 for HCI at the end of the induction phase; p = 0.003 for the maintenance phase). The median progression-free survival of these 6 long-term responders was 75 months (range, 62 to 78). INTERPRETATION AND CONCLUSIONS: Overall, alpha-IFN represents an excellent palliative treatment for most HCL patients. A small subset of these patients could become long-term responders following first-line alpha-IFN therapy alone.

Adult↗

Primary intestinal lymphoma: clinical and therapeutic features of 32 patients.

BACKGROUND AND OBJECTIVE: Lymphomas of the gastrointestinal tract are the most common type of primary extranodal lymphomas, accounting for 5 to 10% of all non-Hodgkin's lymphomas. In particular, primary intestinal lymphomas represent about 15-20% of gastrointestinal lymphomas. New multimodal therapeutic approaches have improved the prognosis of this once deadly disease: we report a retrospective analysis of our experience with 32 cases of primary western intestinal lymphomas, presenting clinical, therapeutical and prognostic data. PATIENTS AND METHODS: From March 1989 to November 1995, 32 patients with untreated primary western intestinal lymphomas were submitted to radical surgery plus polychemotherapy (early stages, I and II; 22 patients), or polychemotherapy alone (advanced stage, III and IV; 10 patients). The most frequent symptoms were abdominal pain, nausea, vomiting and weight loss. The tumor was located in the jejunum in 2 cases (6.2%), in the proximal small bowel in 15 cases (46.9%), in the distal and terminal ileum in 8 cases (25%), in the colon and rectum in 4 cases (12.5%), and multiple sites were found in 3 cases (9.4%). According to histology, 26 patients had high-grade and 6 low-grade non-Hodgkin's lymphoma. RESULTS: Stage I-II patients underwent radical resection of the tumor and chemotherapy; advanced (III-IV) stage patients were treated with chemotherapy alone as first-line approach. Of the 32 patients, 24 (75%) achieved a complete response (CR); according to stage, all stage I-II patients had CR, while only 2 of the 10 stage III-IV patients reached CR. The risk of a lower response rate was significantly correlated with the presence of advanced stage (III-IV) (p = 0.000001). The overall 5-year survival rate was 59%, with a relapse-free survival rate of 72% among the 24 complete responders. INTERPRETATION AND CONCLUSIONS: Intestinal lymphomas differ significantly from their gastric counterpart, not only in pathology, but also with regard to clinical features, management and prognosis. Our experience confirm the efficacy of the surgery-chemotherapy combination in obtaining a good remission rate for localized early primary intestinal lymphoma and indicates that this combination represents the only means for managing complications.

Adolescent↗