Publications (8)59.72 Total impact
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Article: Salvage Therapy With Thalidomide In Patients With Advanced Relapsed/Refractory Multiple Myeloma
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ABSTRACT: Background and Objectives. Few therapeutic options are presently available for patients with multiple myeloma (MM) who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a glutamic acid derivative with anti-angiogenic properties, has been recently proposed as an effective therapy for patients with advanced refractory disease. The aim of this study was to evaluate the activity of thalidomide in a large series of MM patients. Design and Methods. From October 1999 to January 2001, 65 patients (46 males/19 females) from 8 Italian institutions were treated with thalidomide. Twenty-six patients had relapsed after autologous stem cell transplantation, either single (n = 12) or double (n= 12); 38 patients had shown disease progression after greater than or equal to 2 lines of conventional chemotherapy, 2 patients had relapsed after allotransplant, one single patient had not received previous treatment. Sixty-one (93.8%) patients were in stage 111, median beta2 microglobulin was 2.9 mg/L, and median bone marrow plasma cell infiltration was 50%. Thalidomide was initially administered at a dose of 100 mg/day; if well tolerated, the dose was to be increased serially by 200 mg every other week to a maximum of 800 mg/day. Results. The median administered dose of thalidomide was 400 mg/day. WHO grade> II toxic effects were constipation (52%), lethargy (34%), skin rash (11%), peripheral neuropathy (14%) and leukopenia (3%). Sixty patients are presently evaluable for response; of these, 17 (28.3%) showed greater than or equal to 50% reduction in serum or urinary M protein concentration and 11 (18.3%) showed greater than or equal to 25% tumor reduction, for a total response rate averaging 46.6%. After a median of 8 months' follow-up, 15/28 patients are alive and progression-free (at 2 to 16 months), 12 patients have relapsed, and 1 patient died of pulmonary edema while still in partial remission. Among pre-treatment variables that were analyzed for their potential relationship with tumor response, only the concentration of vascular endothelial growth factor (VEGF) in the conditioned media obtained upon culture of bone marrow plasma cells was statistically significant. Plasma cells from patients who responded favorably to thalidomide secreted a significantly lower amount of VEGF than plasma cells from resistant patients (126.45 ± 165 pg/mL vs 227.11 ± 70 pg/mL, p = 0.04). Interpretation and Conclusions. These data confirm that thalidomide is active in patients with advanced relapsed/ refractory MM and represent the basis for ongoing clinical trials aimed at testing the role of this drug as front line therapy for newly diagnosed disease.Journal of the Peripheral Nervous System 08/2002; 7(3):209 - 209. · 2.80 Impact Factor -
Article: Salvage therapy with thalidomide in multiple myeloma patients relapsing after autologous peripheral blood stem cell transplantation.
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ABSTRACT: The introduction of high-dose therapy with stem cell support has significantly improved the outcome of patients with multiple myeloma (MM) in terms of increased complete remission (CR) rate and extended survival, both disease-free and overall. Few options, however, are presently available for patients who relapse after single or double autologous stem cell transplantation (SCT). Thalidomide, a glutamic acid derivative with anti-angiogenetic properties, has been recently proposed as salvage treatment for such patients. The present study was aimed at evaluating thalidomide as single agent therapy for patients who had previously received autologous peripheral blood stem cell transplantation. From October 1999 to August 2000, 11 patients (7 males/4 females) who had relapsed after single (n = 4) or double (n = 7) autologous peripheral blood SCT were enrolled in the trial. Thalidomide, always employed as a single agent, was initially administered at a dose of 100 mg/day; if well tolerated, the dose was increased serially by 200 mg every other week to a maximum of 800 mg/day. The median administered dose was 600 mg/day. WHO grade > II toxic effects were constipation, lethargy, and leukopenia. Four patients (36%) showed > 50% reduction in serum M protein concentration and 4 showed > 25% reduction, for a total response rate averaging 72%. After a median follow-up of 5 months, 3 out of 8 responding patients are alive and progression-free and 5 patients have relapsed. INTERPRETATION AND CONCLUSIONS; These data confirm that thalidomide is active in poor-prognosis MM patients such as those relapsing after autologous SCT, and could thus deserve further testing in combination therapy.Haematologica 04/2001; 86(4):409-13. · 6.42 Impact Factor -
Article: Long-term follow-up of hairy cell leukemia patients treated with 2-chlorodeoxyadenosine.
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ABSTRACT: The management of patients with hairy cell leukemia (HCL) has evolved significantly over the past two decades. In fact, both 2'-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-CdA) induce complete response (CR) in the majority of the patients with HCL. However, fewer data exist on the long-term follow-up of patients who have undergone the characteristically brief exposure to 2-CdA therapy. Thus, it is important to evaluate such long-term outcome data in order to increase understanding of the efficacy of this agent in the management of HCL. We reviewed the long-term follow-up data of 23 HCL patients pretreated with a-interferon and then treated with 2-CdA administered as a single continuous IV infusion for 7 days at the dose of 0.1 mg/kg/day in our institute between January 1991 and February 1992. Of 23 patients, 19 (83%) achieved a CR and 4 (17%) a partial response (PR), with an overall response rate of 100%. After a median follow-up of 102 months (range: 96-108), there have been 9 (39%) relapses. In the PR subset 100% of patients relapsed within the first 45 months of follow-up. In the group of patients who obtained a CR, 26% relapsed; all these relapses occurred between 54 and 86 months. Overall, the median time to relapse was 54 months (range: 16-86). All relapsed patients were re-treated with 2-CdA at the dose of 0.15 mg/kg/day for 5 days in a 2-hour infusion, and 67% and 22% then obtained CR or PR, respectively. The median duration of this second response was 48 months (range: 22-80). All but one of these patients are still maintaining the second response to 2-CdA. The 9-year overall and the relapse-free survivals are 91% and 70%, respectively. In HCL patients a single dose of 2-CdA induces a long-term CR with a 9-year survival > 90%. Over 50% of patients appear to be clinically cured by this procedure, but the lack of a long-term plateau in the relapse-free survival curve means caution on this point is still warranted.Haematologica 09/2000; 85(9):922-5. · 6.42 Impact Factor -
Article: Efficacy of fludarabine and mitoxantrone (FN) combination regimen in untreated indolent non-Hodgkin's lymphomas.
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ABSTRACT: In the last years, fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of previously treated low-grade non-Hodgkin's lymphomas (LG-NHL). The aim of this study was to define the therapeutic efficacy and toxicity of a combination of FLU and mitoxantrone (FN regimen) in untreated LG-NHL. We used a two-drug combination of FLU (25 mg/m2 i.v. on days 1 to 3) and mitoxantrone (10 mg/m2 i.v. on day 1) to treat 27 previously untreated patients with LG-NHL, Chemotherapy was repeated every four weeks for a total of six cycles. Among 27 patients, 17 (63%) were diagnosed with follicular, 6 (22%) with small lymphocytic, and 4 (15%) with immunocytoma subtypes. Of the 27 patients, 18 (67%) achieved complete response (CR) and 6 (22%) partial response, while the remaining 3 (11%) showed no benefit from the treatment. Regarding histology, in the follicular subtype we observed an overall response rate of 94%, with a 76.5% CR rate. The estimated two-year relapse-free survival was 83%, and overall survival was 92%. Hematologic grade 3-4 toxicity was seen in only five (3.3%) patients; no opportunistic infections or deaths were associated with the administration of the FN regimen. These preliminary data show that the FN regimen is a very active, well-tolerated combination chemotherapy for untreated patients with advanced LG-NHL.Annals of Oncology 04/2000; 11(3):363-5. · 6.43 Impact Factor -
Article: Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.
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ABSTRACT: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.Journal of Clinical Oncology 03/2000; 18(4):773-9. · 18.37 Impact Factor -
Article: Fludarabine-based chemotherapy in untreated mantle cell lymphomas: an encouraging experience in 29 patients.
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ABSTRACT: A prospective study to evaluate the role of fludarabine alone or in combination with idarubicin in untreated patients with mantle cell lymphoma (MCL). Twenty-nine untreated patients with mantle cell lymphoma were stochastically treated with intravenous fludarabine at a dose of 25 mg/m(2)/day for 5 days (11 patients) or with a combination of fludarabine and idarubicin (FLU-ID) (fludarabine 25 mg/m(2) i.v. on days 1 to 3 and idarubicin 12 mg/m(2) i.v. on day 1 (18 patients). For both regimens, cycles were given at three-week intervals for a total of six courses. According to the International Prognostic Index, the most part of high-intermediate and high risk factor patients were in the FLU-ID subset: 7 (39%) patients vs. 2 (18%) in the fludarabine alone subset. Of the 29 patients, 8 (28%) obtained a complete response and 10 (35%) a partial response, with an overall response rate of 63%. The remaining 11 (37%) patients did not respond to the therapy. The overall response rates were 64% (7 patients) in the fludarabine group and 61% (11 patients) in the FLU-ID group. The complete response rate was 27% (3 patients) for fludarabine and 28% (5 patients) for FLU-ID. The toxicity was mild in terms of neutropenia and infections, and no fatalities occurred due to drug-induced side effects. These results suggest the efficacy of fludarabine alone or in combination with idarubicin in MCL patients. It will be important to increase this experience and to assess other fludarabine-containing regimens, in particular with cyclophosphamide plus idarubicin and with mitoxantrone and or cyclophosphamide, to test the true role of this approach in MCL.Haematologica 12/1999; 84(11):1002-6. · 6.42 Impact Factor -
Article: How do patients with aggressive non-Hodgkin's lymphoma treated with third-generation regimens (MACOP-B and F-MACHOP) fare in the long-term?
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ABSTRACT: To examine the long-term clinical course and prognostic factors of patients with advanced aggressive non-Hodgkin's lymphoma (NHL) treated with third-generation regimens as front-line chemotherapy. A total of 348 patients aged <60 years received MACOP-B or F-MACHOP regimen between September 1988 and August 1993 for advanced stage aggressive NHL. Of these, 249 (71.5%) obtained a complete response (CR); 65/249 (26%) subsequently relapsed. The CR rates for MACOP-B and F-MACHOP were 70.5% and 72%, respectively, while the relapse-free survival rates (RFS) at 9 years were 66% and 74%, respectively. The overall survival rate at 9 years was 61% for MACOP-B and 67% for F-MACHOP patients. Of the relapses, 78.5% were early (<24 months) and 21.5% late. Eleven out of 65 (17%) patients are in continuous second CR with a median follow-up of 45 months; most of them have been salvaged with high-dose therapies. The validity of the International Prognostic Index was confirmed in long-term analysis. With a 9-year RFS, it is possible to consider cured 50% of the patient with aggressive NHL treated with a third-generation regimen. About a quarter of the CRs relapse and late relapse occurs in roughly 20% of all relapsed patients. In these patients high-dose chemotherapy followed by autologous bone marrow or hematopoietic stem cell transplantation seems to be a very reliable approach in terms of long-term second CR. Finally, the IPI score maintains its pivotal role in terms of stratifying patients according to different risk subsets also in long-term analysis.Haematologica 11/1999; 84(11):996-1001. · 6.42 Impact Factor -
Article: The role of positron emission tomography (PET) in the management of lymphoma patients.
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ABSTRACT: Treatment of both Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) with abdominal presentation at the time of diagnosis is often followed by detection of residual masses by computed tomography (CT). However, CT is usually unable to discriminate between residual tumor and fibrosis/necrosis. We investigated the ability of fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to differentiate between residual active tumor tissue and fibrosis. Forty-four patients with HD or aggressive NHL presenting abdominal involvement (41% with bulky mass) were studied with CT and PET at the end of chemotherapy +/- radiation therapy. After treatment, seven patients had negative PET and CT, and none of them relapsed. The remaining 37 patients all had positive CT (abnormalities < or = 10%). All of the 13 who also had positive PET relapsed (100%). By contrast, there was only 1 (4%) relapse among the 24 patients who were positive at CT but negative at PET. The two-year actuarial relapse-free survival rate was 95% for those with negative PET compared with 0% for positive PET patients (P < 0.000000). In lymphoma patients with abdominal masses who present CT positivity at restaging, PET should be considered the noninvasive imaging modality of choice for differentiating early recurrences or residual disease from fibrosis.Annals of Oncology 10/1999; 10(10):1181-4. · 6.43 Impact Factor
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Institutions
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1999–2000
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University of Bologna
- Institute of Haematology
Bologna, Emilia-Romagna, Italy
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