High-dose mitoxantrone plus melphalan (MITO/L-PAM) as conditioning regimensupported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: high tolerability with reversible cardiotoxicity

Hematological and extrahematological toxicity of high-dose (hd) mitoxantron e (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patien ts (87 at disease onset). Autograft was the final part of a hd-sequential ( HDS) chemotherapy program, including a debulkying phase (1-2 APO +/- 2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methot rexate (or Ara-C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd-MITO, given at 60 mg/m(2) on day -5; (2) hd-L-PAM, given at 180 mg/m(2) on day -2; (3) PBPC autograft, with a median of 11 x 10(6) C D34(+)/kg, or 70 x 10(4) CFU-GM/kg, on day 0. A rapid hematological recover y was observed in most patients, with ANC >500/muL and Plt >20 000/mul valu es reached at a median of 11 and 10 days since autograft, respectively. The good hemopoietic reconstitution allowed the delivery of consolidation radi otherapy (RT) to bulky sites in 53 out of 57 candidate patients, within 1 t o 3 months following autograft; five of these patients required back-up PBP C re-infusion due to severe post-RT pancytopenia. Few severe infectious com plications were recorded. There was one single fatal event due to severe pa ncytopenia following whole abdomen RT, Cardiac toxicity was evaluated as le ft ventricular ejection fraction (LVEF), monitored by cardiac radionuclide scan. LVEF prior to and after autograft was significantly reduced (median v alues: 55% vs 46%) in 58 evaluated patients; however, a significant increas e to a median value of 50% was observed in 45 patients evaluated at 1 to 3 years since autograft. At a median follow-up of 3.6 years, 92 patients are alive, with a 7-year overall survival projection and 6.7-year failure-free survival projection of 77% and 69%, respectively. We conclude that a condit ioning regimen with hd-MITO/L-PAM fits well within the HDS program, It impl ies good tolerability and reversible cardiotoxicity and it may have contrib uted to the good long-term outcome observed in this series of patients.