Therapeutic and Mobilizing Activity of a Vinorelbine, Ifosfamide and Cytarabine Regimen (VIHA) as Salvage Regimen In Resistant/Relapse Non Hodgkin Lymphoma (NHL)

The identification of active regimens sharing clinical and mobilizing activity are warranted NHL patients (pts) at high risk at onset or at relapse, as induction therapy before peripheral blood stem cell transplantation (PBSCT). Vinorelbine (VNR), ifosfamide (IFX), and cytarabine (ARA-C) are of proved efficacy in this setting.

From November 1999 to September 2008, 115 pts underwent the VIHA regimen: VNR 25 mg/mq day 3, IFX 2500 mg/mq days 1–3, and ARA-C 2 gm/mq bid days 2–3. Pts older than 60 years, were given the same regimen at 75% of doses. A total of 4 cycles was repeated every 21 days with G-CSF support from day 7 to day 12 or up to the apheresis. Mobilization was performed from the 3rd cycle, in patients withat least partial remission (PR), achieved after cycle 2. All cases with at least stable disease (SD) at the end of VIHA induction and with a CD34+ cell collection of > 1.5 × 10<6/Kg were then candidated to PBSCT.

Main clinical characteristics: median age 47 (range 28–73) with 36 pts older 60 years, aggressive histology 73, indolent histology 42, primary refractory disease 44, relapsed disease 71, stage III or IV 42, bone marrow involvement 20, sIPI > 2 13. Seventy-seven pts had received at least two lines of chemotherapy before VIHA.

Sixty-seven patients (59%) obtained an objective response (OR) with 48 (42%) of these obtained complete remission (CR) according to CT-scan criteria. Seventy-four patients entered PBSCT and 41 did not for the following reasons: 15 due to unplanned PBSCT, 13 pts failed mobilization, one for toxic deaths, and the others for disease progression. With a median follow-up of 47 months, 4-year progression free survival (PFS) and overall survival (OS) are 30% and 39%, respectively. In univariate analysis, only the histologic category (aggressive vs indolent) was a predictive factor of response (p.001) and survival (p<.0001). In multivariate analysis, only elevated IPI at relapsed (> 2) was a significant negative predictor. Interestingly, there was no difference in OR, PFS and OS between patients treated with full dose or reduced dose VIHA.

As concerns stem cell mobilization, in 80 mobilized pts, median number of CD34+ cells collected was 7.1 × 10⁶/Kg (range 1.5–45) after a median of 2 (1-3) apheretic procedures.

Among more than 240 VIHA cycles analyzed for haematological toxicity 86% of full dose VIHA required platelet transfusions and 50% RBC transfusions, as compared to 46% (p<.0001), and 34% (p0.03), of reduced dose VIHA, respectively. Febrile neutropenia complicated 27% of all cycles and there were 19 documented infections. Thirty-five per cent required Hospitalization for documented infections or febrile neutropenia was necessary in 35% of full-dose VIHA cycles and in 16% of reduced VIHA cycles, (p.01). There was only one death-related therapy.

VIHA shows clinical and mobilizing activity comparable to better known salvage chemotherapy regimens; otherwise our data suggest to use as well the reduced dose regimen, which shares clinical activity and lower toxicity profile. The high CD34 mobilizing activity is notheworthy.

No relevant conflicts of interest to declare.