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Elderly patients with aggressive Non-Hodgkins Lymphoma An age adjusted high dose chemotherapy with autologous stem cell transplantation allows an adequate PBPC yield with low toxicity and promising results



Elderly patients with aggressive Non-Hodgkins Lymphoma An age adjusted high dose chemotherapy with autologous stem cell transplantation allows an adequate PBPC yield with low toxicity and promising results



Blood 98(11 Part 2): 400b-401b



Introduction: elderly patients (>60 years) are usually considered not eligible for HDC. However, most of them might tolerate ASCT with "age-adjusted" HDC regimens. Patients and methods: patients ranged between 61 and 70 years with aggressive NHL in relapse/progression or at diagnosis with intermediate/high or high risk according to IPI and/or BM involvement were enrolled into this study. The therapeutic scheme includes three phases: A) 6 weeks of P-VEBEC chemotherapy in patients at diagnosis; Abis) 2 courses of DHAP (at 75% of the total dose) for patients in relapse/progression or with slow response after P-VEBEC; B) intensification with a 2-day courses of Mitoxantrone 8 mg/m2 plus high-dose Cytarabine (HD-AraC) 1500 mg/m2/12hr plus Dexamethasone 4 mg/m2/12hr and G-CSF 5 mug/Kg/day form day +3 to harvest peripheral blood progenitor cells (PBPC); C) ASCT conditioned by BCNU 200 mg/m2 day -6, Ara-C 200 mg/m2/12hr plus VP-16 100 mg/m2/12hr days -5 to -3, Melphalan 120 mg/m2 day -2, reinfusion of at least 5X106/Kg CD34+ cells, G-CSF 5 mug/Kg from day +1 to haematological engraftment. Results: since January 1998, twenty-six patients have been enrolled: median age 65 years (range 61-70), 20 males, 6 females, 12 B-DLCL de novo, 8 transformed follicular, 3 mantle cell, 1 anaplastic and 2 peripheral T-cell NHL. Twelve patients were in relapse/progression: 9 in first early relapse (<12 months), 1 in second, 1 in partial remission and 1 in progression; all patients showed at relapse/progression an advanced disease; 10/12 patients were previously treated with antracycline containing regimens. Fourteen patients were treated at diagnosis: 9 were at intermediate/high or high risk according to IPI criteria, 10 had bone marrow involvement. Up to now, 24/26 are evaluable for clinical response and toxicity. An adequate PBPC yeld (>5X106/Kg) was obtained in 21/24 patients with a median of 13X106/Kg CD34+ cells (range 5.2-45). PBPC yeld was not achievable in 3 patients: two were heavily pre-treated with Chlorambucil and the last one progressed while on therapy. 20/24 patients were autografted. Four patients did not receive ASCT: two because of progressive disease and two due to indequate PBPC yeld. The median times to achieve neutrophils >0.5X109/l and platelets>50X109/l were 7 days (range 4-9) and 18 days (range 2-79) respectively. No toxic deaths were observed. Grade 3 and 4 WHO toxicities were: mucositis in 2 patients and infections in 4 (2 bacterial, 1 pulmonary aspergillosis, 1 CMV infection). Clinical response in the 12 patients in relapse/progression was as follows: 6 CR, 1 PR, 5 NR. Among the 12 patients treated as first line therapy, at diagnosis, 10 patients achieved CR and 2 NR. Conclusions: these preliminary results suggest that a good PBPC yeld is achievable after an intensified chemotherapy with Mitoxantrone and HD-AraC in elderly patients at diagnosis or pre-treated. An "age-adjusted" therapy with modified HDC and BEAM regimen followed by ASCT is feasible and effective with low toxicity also in elderly patients with aggressive NHL.

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