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CR, complete remission; PR, partial remission; PD, progressive disease; TRM, therapy-related death; NA: not available.

CR, complete remission; PR, partial remission; PD, progressive disease; TRM, therapy-related death; NA: not available.

EFS rate for patients who underwent transplantation was 68%. Predictors for outcome included B symptoms, extranodal disease, and CR duration of <1 year. Highdose ifosfamide and vinorelbine produced an overall response rate of 83%, with 45% complete and 38% partial responses after a median of two cycles55; the main toxic effect of these regimens was grade III-IV neutrope-nia, documented in 65% of cycles, with a median duration of 4-7 days. Almost all these standard-dose regimens were followed by PBPC collection and high-dose therapy with autologous stem cell rescue; after engraft-ment many patients received radiotherapy for residual disease. Of particular interest is the IEV (ifosfamide, epirubicin, and etoposide) combination57; this regimen was highly effective in patients relapsing after first second-line chemotherapy. Responsive patients were subsequently treated with radiotherapy. In these advanced patients, IEV was able to induce OS, RFS, and FFP of 18, 44, and 22%, respectively.

More recently, gemcitabine, a new pyrimidine antimetabolite was shown to have remarkable activity against solid tumors such as those of pancreas, lung, and bladder and to be active in vitro against leukemia and lymphoma cell lines.68 When used as a single agent, gemcitabine is active in Hodgkin's lymphoma5859 and in a variety of histologic subtypes of non-Hodgkin's lymphoma, with a favorable toxicity profile compared with other cytotoxic agents.5669 In phase II studies in relapsed/refractory Hodgkin's lymphoma the drug was given on days 1, 8, and 15 at a dose of 1200 mg/m2, with a schedule every 28 days, for a total of six cycles.59 The overall response rate was 39%, with 9% CRs. In another study,58 the overall response rate was 43%, with 14% CR ; the patients who relapsed after a remission longer than 12 months had a better OS rate than those who relapsed earlier (67% vs 25%). In both studies the major toxicity was hematologic, with a minority of patients experiencing a grade IV toxicity. In no study did treatment-related deaths occur. According to these results this drug has been included in several salvage regimens for resistant/relapsing Hodgkin's lymphoma.

The addition of cisplatin to gemcitabine has demonstrated synergistic activity in vitro and this combination has become the standard in the treatment of advanced bladder and non-small cell lung cancer.70 Given the moderate toxicity observed with these drugs when used at conventional doses, both have been incorporated with dexamethasone into the gemcitabine, dexametha-sone, cisplatin (GDP) regimen.71 The overall response rate achieved after the GDP regimen is 70%, (17% CRs); hematologic toxicity was mild (grade III neutropenia: 9%; grade III thrombocytopenia: 13%) and all patients successfully mobilized PBPC, with a median 10.6 X 106 CD34+ cells/kg.60

Gemcitabine has also been associated with ifosfamide and vinorelbine in the IGEV combination. In the original experience in 17 heavily pretreated patients (chemo + radiotherapy), the overall response rate was 94%61 and the median number of CD34+ cells collected was 10.9 X 106/kg; in about 60% of patients, a single leukapheretic procedure was able to reach the number of CD34+ cells necessary for the transplantation procedure. No treatment-related death was observed. The experience with the IGEV regimen has been widely confirmed also for its acceptable toxicity.

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