Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation

Abstract

Summary:There is growing interest in autologous stem cell transplantation (ASCT) for elderly patients with acute myeloid leukemia (AML). While mortality and toxicity from ASCT have been reduced, relapse rate is still high. In a prospective study, we investigated the feasibility of a new conditioning regimen consisting of high-dose idarubicin plus busulfan in AML patients aged over 60 years undergoing ASCT. A total of 14 patients (median age: 64 years) received 2 days continuous infusion of idarubicin at 20 mg/m 2 /day, followed by 3 days of oral busulfan (4 mg/kg/day) as conditioning. No case of transplantrelated mortality occurred. The median number of days to neutrophil (40.5 Â 10 9 /l) and platelet (420 Â 10 9 /l) recovery was 11 and 12, respectively. Cardiac toxicity was absent, while 12 patients (86%) had grade 3-4 mucositis. After a median follow-up of 9 months from ASCT, nine of 14 patients are alive in continuous complete remission (CR), four have relapsed at 3, 6, 8 and 9 months, and one died in CR1 from gastric cancer. Our data demonstrate the feasibility of a conditioning regimen based on high-dose idarubicin plus busulfan in elderly AML patients. Results concerning reduction of relapse rate need confirmation in a larger series with longer follow-up. The prognosis of acute myeloid leukemia (AML) in older individuals is still poor, due to either lower complete remission (CR) rate or higher incidence of relapse as compared to young/adult patients. [1][2][3][4][5] In an attempt to reduce the relapse rate, there is a growing interest in autologous stem cell transplantation (ASCT) for elderly patients with AML. 6,7 Nevertheless, despite a progressive reduction in transplant-related mortality (TRM) and toxicity, the overall relapse incidence after ASCT remains high. The combination of busulfan and cyclophosphamide, originally designed for allogeneic SCT by the Baltimore team (BuCy) 8 and then its modification by the Columbus team (BuCy2), 9 remains the most frequently used conditioning regimen for ASCT in AML. In the autologous setting, alternative chemotherapy combinations have been proposed to induce superior antileukemic activity and/or reduce toxicity. [10][11][12] In particular, a recent survey from the European Cooperative Group for Blood and Marrow Transplantation (EBMT) reported that the BAVC regimen (BCNU 800 mg/ m 2 , amsacrine 150 mg/m 2 /day for 3 days, VP-16 150 mg/m 2 / day for 3 days and ara-C 300 mg/m 2 /day for 3 days) demonstrated comparable survival with lower TRM. 13 In young/adult AML patients, we previously demonstrated the feasibility and efficacy of an original conditioning regimen, called IBu, consisting of high-dose idarubicin (IDA) administered at 20 mg/m 2 /day as continuous infusion (CI) for 3 days (day -13 to day -11) followed by oral busulfan (Bu) given at 4 mg/kg/day from day -5 to day -2. 12 This regimen relies on the adoption of high-dose CI idarubicin as well as on the removal of cyclophosphamide to increase antileukemic activity.Here, we report results of a prospective st...

Age has no influence on mobilization of peripheral blood stem cells in acute myeloid leukemia

“…Most patients were conditioned to ASCT with c.i. idarubicin and oral busulphan with a schedule adapted by age as previously described [24,25] and there was no difference between young adult and elderly patients as transplant related mortality and haematopoietic recovery is concerned (data not shown).…”

Feasibility of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia

“…Following consolidation, G-CSF was given at a dose of 10 mg kg 71 from day 15 with the aim of shortening neutropenia and mobilizing CD34þ cells. All patients in whom collection of CD34þ cells was successful (42 6 10 6 kg 71 ) were programmed to be given ASCT with a conditioning regimen consisting of high dose intravenous continuous infusion idarubicin plus busulphan, as previously described [28]. More in detail, high-dose idarubicin administered at 20 mg m 72 per day as CI for 2 days (day -11 to day -10) followed by oral busulphan given at 4 mg kg 71 per day from day -4 to day -2.…”

Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan

“…In addition, a substantial reduction of morbidity and mortality has been definitively confirmed following the adoption of PBSC [13]. In a small series of 14 patients, we previously described results achieved with ASCT after conditioning with an original combination regimen including Ida and Bu [22]. Such a regimen was specifically designed for AML, with the aim of reducing relapse rate which, differently from toxicity, remains substantially unmodified in patients autografted with PBSC.…”

“…In the autologous setting, alternative chemotherapy combinations have been proposed with the aim of inducing a superior anti-leukaemic activity [20,21]; in particular, in a preliminary study on older AML patients we reported the feasibility and the potential efficacy of a new conditioning regimen, consisting of a combination of 2 days continuous infusion (c.i.) idarubicin (IDA) at a dose of 20 mg/m 2 followed by 3 days standard oral dose busulphan (Bu), termed BuI [22]. Here we report therapeutic results from a larger series of 40 AML patients older than 60 years with a longer follow up who were autografted in CR1 after conditioning with BuI regimen.…”