Feasibility of Autologous Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukaemia Treated with Continuous Sequential Infusion of Fludarabine Plus Cytarabine (CI-FLA). Session Type: Publication Only

Felicetto Ferrara, Giuseppina Mele, Catello Califano, Salvatore Palmieri, Barbara Pocali, Paolo Danise, Carolina Copia, Alfonso M. DArco

Author address: 

Hematology and Stem Cell Unit, Cardarelli Hospital, Napoli, Italy; Onco-hematology, Umberto I Hospital, Nocera Inferiore, Italy


Autologous stem cell transplantation (ASCT) is increasingly used in acute myeloid leukemia (AML); however, due to toxicity of induction/consolidation treatment, early relapse and insufficient collection of CD34+ cells, ASCT is given to a small minority of older patients. We investigated the feasibility of ASCT from a series of 44 newly diagnosed patients, treated with combination of fludarabine (F) plus cytarabine (ARA-C) given as continuous sequential infusion. Patients were required to have non M3 AML and age more than 60. F was given at a loading dose of 10 mg/m2 over 15 min at day 0 followed by a continuous infusion (CI) of 20 mg/m2/24 hours for 72 hours, ARA-C at a loading dose of 390 mg/m2 over 15 min three hours and half after F and then as CI over 96 hours at 1440 mg/24 hours for a total of 96 hours. G-CSF was added at day +15 at 5mg/kg. Patients in complete remission (CR) were programmed to receive an additional identical course of CI-FLA. However, after the first 20 patients, consolidation was reduced by one day because of excessive toxicity. Following consolidation, G-CSF at 10 mg/kg was given from day + 15 in order to shorten neutropenia and mobilize CD34+ cells. 44 patients (median age 69 years, range 61-81) received the therapeutic program. In 17 patients (39%) a previously diagnosed myelodysplastic syndrome (MDS) preceded the onset of AML, while in 9 (20%) multilinear dysplastic abnormalities were present in apparently de novo cases. Among 36 patients with evaluable cytogenetics (82%), 17 had normal karyotype (47%), 12 complex karyotype (33%) and 7 other chromosomal abnormalities (19%); 38 patients (86%) were affected by concomitant disease requiring specific treatment. Overall, 28 patients achieved CR (64%), all after one course of CI-FLA. There were 8 induction deaths (18%), while 8 patients (18%) were refractory to induction. All patients experienced febrile neutropenia requiring broad spectrum empiric antibiotic and/or antifungal therapy as well as platelet and blood transfusions. Among remitters, 23 out of 28 patients received the programmed consolidation course, while in 5 cases (11%) therapy was discontinued due to induction toxicity. Following consolidation, 16 patients were monitorized for the mobilization of CD34+ cells, collection being successful in 11 (69%). The median number of CD34+ cells collected was 9.17 (2.5-42.7), after a median number of 2 aphereses. Overall, 8 patients (18%) have received ASCT, the only reason for exclusion being early relapse. Toxicity of ASCT was acceptable with no case of transplant related mortality. In conclusion, this study demonstrates that continuous sequential infusion of F + ARA-C is an effective and relatively well-tolerated regimen for elderly patients with AML. The collection of CD34+ cells is successful in 69 % of eligible cases while ASCT is feasible in 73 % of mobilizing patients, the only reason of exclusion being early relapse. Overall, 8 out of 44 patients (18%) were actually given ASCT. These results compare favorably with anthracyclines + ARA-C in terms of CD34+ cell collection and feasibility of ASCT in AML of the elderly. Toxicity of induction/consolidation treatment and early relapse remain the major obstacle for AS

abstract No: 


Full conference title: 

American Society of Hematology 45th Annual Meeting
    • ASH 45th (2003)