The prognosis of acute myeloid leukemia (AML) is poor in the elderly due to low complete remission (CR) rate and high relapse rate. Aiming at reducing relapse, autologus stem cell transplantation (ASCT) is increasingly used in older AML patients. However, toxicity is considerable and relapse rate remains high after conditioning with the classical combination of Busulphan (Bus) and Cyclophosphamide. In young/adult patients, we previously demonstrated the feasibility of an original conditioning regimen, called IBu, consisting of a combination of high dose Idarubicin (IDA) administered at 20 mg /m2/day as continuous infusion (ci) from day 13 to 11, followed by oral Bus at 4 mg/kg/day form day 5 to 2. Here we report data from a series of 13 AML patients conditioned to ASCT with a reduced schedule of IBu regimen, (ci IDA at 20 mg /m2/day from day -12 to 11 and oral Bu at 4 mg/kg/day from day -4 to 2), specifically designed for elderly patients. Patients with acute promyelocytic leukemia (APL) in CR1 were excluded. 13 patients received ASCT, after conditioning with IBu. The median age was 64 years (61-74); 11 (85%) were autografted in CR1, 2 in CR2, including 1 APL. Among CR1 patients, 8 had normal karyotype, 3 complex karyotype; as concerns CR2, the patient with APL had t(15;17), one had 6p- and one complex karyotype. All transplants were performed in single or double conventional rooms using peripheral blood stem cells (PBSC) collected after consolidation followed by G-CSF. Prophylaxis against infection consisted of oral cyprofloxacin, while neither antiviral nor antifungal prophylaxis were adopted. The median number of CD34 positive cells infused was 5.6x106/kg (2.5-19). In all patients left ventricular ejection fraction (LVEF) was evaluated before and after ASCT. All patients experienced full engrafment. The median number of days for stable recovery of neutrophils to 0.5x109/L and platelets to 20x109/L was 11 (9-19) and 12 (6-38), respectively. The median number of platelet and blood units transfused was 3 (1-7) and 4 (1-5), respectively. The only episodes of WHO grade 3-4 extra-hematological toxicity consisted of stomatitis requiring total parenteral nutrition in 9 patients (69%) and resolved at the time of hematopoietic recovery. Fever occurred in 12 patients; there were 10 cases of fever of unknown origin and two documented infections, one bacterial pneumonitis and one pulmonary aspergillosis, both resolved with antibiotic and antifungal therapy after hematopoetic recovery. There was no case of transplant related mortality; of note, LVEF examination post-ASCT did not reveal cardiac toxicity in any patient. At the time of writing with a median follow up of 12 months (range 2-46), 9 patients are in continuous CR1, while 3, two of which autografted in CR2, have relapsed at 3, 6, and 8 months from ASCT, respectively, and have died from progressive disease. One patient died from gastric cancer, while in CR1. Median overall and disease free survival have not yet been reached after a median follow up of 12 months from transplantation and 16 months from diagnosis. In conclusion, our data demonstrate acceptable toxicity of the combination of idarubicin plus busulphan as conditioning to ASCT in elderly AML patients and suggest a possible reduction of relapse rate. These very encouraging results need to be confirmed in a larger series with longer follow-up.
Full conference title:
American Society of Hematology 45th Annual Meeting
- ASH 45th (2003)