Intensified Chop (CHOP14) Plus Rituximab in the Treatment of Elderly Patients with Aggressive and High Risk Non Hodgkin’s Lymphoma (NHL).

The results of treatment of aggressive NHL in elderly patients is relatively poor. The use of protocol specifically devised for eldery patients can reduce hematological and extrahematological toxicity but yield worst results, particularly in high-risk IPI patients. Recentely Coiffier et al. have showed that the standard therapy for patients over 60 years with aggressive lymphoma was rituximab plus CHOP. With the aim to improve dose intensity in elderly large cell lymphoma patients and intermediate-high or high-risk IPI score we planned treatment with rituximab 375 mg/sqm on day 0 and CHOP therapy on day +2 given every 2 weeks, with G-CSF starting from day + 7 to + 11 and a profilaxis with cotrimoxazole twice weekly and itraconazole 100 mg day. With an intention to treat analysis we have included in the study, from June 2002 to June 2004, 25 patients with the following characteristics: IPI score 2 in 8 patients (32%), score 3 in 10 (40%) and score 4–5 in 7 (28%). Two patients had diagnosis of follicular grade III lymphoma and the other 23 diffuse large B-cell lymphoma. Eighteen patients (72%) had abnormal value of LDH and 18 patients had one or more extranodal sites involved. The median age was 64 years (60–76), seven patients (28%) were stage II, four (16%) were stage III and fourteen (56%) were stage IV. The aims of the present study were: 1) feasibility 2) toxicity 3) response to therapy. Twenty-two patients completed the estabilished 6 cycles and were evaluable, one patient stopped the treatment after three cycles due to infections the remaining two patients are in treatment. Six patients delayed one cycle and one patient two cycles, due to trombocytopenia or neutropenia. Only eight out 135 cycles were delayed (6%). Sixteen out 23 (70%) patients obtained complete remission (CR) and after a median follow-up of 11 months (1 – 22 months) the disease-free survival was 79%, three patients (19%) relapsed. Two of these patients died rapidly after relapse and one obtained a second CR. Three out 6 patients with a partial response obtained a CR after a salvage therapy, two died and one is still in therapy. With a median follow-up of 15 months (3–25 months) the overall survival was 78%. No remarkable extrahematological toxicity was observed, in particular, as regards cardiotoxicity, we did not observe significant variation of left ventricular ejection rate in comparison with the diagnostic ones, except one patient who, after the sixth cycle, presented a significant reduction of left ventricular ejection which rapidly recovered after he was admitted at hospital. In conclusion we observed that dose intensified CHOP with rituximab was feasible and lack of severe toxicity in elderly patients with aggressive and high risk prognosis lymphoma.