High Dose Chemotherapy (HD CHT) Followed by Autologous PBPC Transplant in Elderly ANLL Patients.
Authors: Capelli Debora , Troiani Emanuela , Discepoli Giancarlo , Poloni Antonella , Montanari Mauro , Catarini Massimo , Centurioni Riccardo , Alesiani Francesco , Brunori Marino , Lucesole Moira , Leoni Pietro , Olivieri Attilio 
Published: October 2019

Abstract
Poor tolerance of aggressive chemotherapy and intrinsic disease resistance of ANLL in Elderly patients strongly impair the achievement of successful responses in this setting. Moreover, even after the achievement of CR, the intensive consolidation with autotransplantation is feasible in very few cases. We used Amifostine as cytoprotective agent in addition to a regimen containing HD Idarubicine (40 mg/sqm) and HD ARA-C (3 g/sqm for 5 days), the so-called “Memorial”. We treated 35 elderly patients (median age: 66, range: 56–78). Amifostine (740 mg/sqm IV) was administered at day 3, followed by Idarubicin. Patients aged more than 70 yrs received 30% reduced schedule. Karyotype was normal in 18 pts, unfavorable in 12 pts, unevaluable in 5 pts. Complete remission was observed in 24 patients (70.6%). The response rate was 78% (14/18) and 41% (5/12) in the intermediate and the poor prognosis cytogenetic groups respectively. Neutrophil (> 1500/ml) and platelet (>50,000/ml) recoveries were achieved at day 16 (range: 12–36) and 17 (range: 11–52) respectively. We observed one toxic induction death due to infection and other 21 grade III infectious episodes which responded to antibiotic treatment. Grade III–IV oral mucositis was observed in 3 patients. Twentyfour patients underwent a consolidation course with FLAG + Daunoxome (80 mg/sm i.v. day 1 and 2); a successful mobilization was achieved in 12 out of the 20 responder patients with a median collection of 6.6 x 106 CD34+/kg (range 4–14). All these patients were successfully autotransplanted with a conditioning regimen including Busulfan 9 mg/m2, Melphalan 120 mg/m2 in combination with Amifostine and Daunoxome 160 mg/m2. Transplant related mortality was 25% (infectious complication in one patient, congestive hearth failure in one case and severe mucositis in the other case). Haematological recovery was complete and fast in all patients. Grade III–IV extrahematological toxicity was mainly due to mucositis (8%), and infections (33%). The sequence HD CHT and autologous transplant determined a final CCR rate of 23% with a median follow-up of 12 months (range 1–31); two relapsed patients are still alive while 25 patients died, 5 for treatment related causes (14%), 20 for disease progression. We observed a 21% 3 years OS with a 27% in patients with intermediate prognosis kariotype versus 16% in the unfavorable group (p=0.03). The prognostic role of kariotype was not confirmed when 3 years DFS was analysed in the 24 responder patients: 25% vs 22% in the intermediate prognosis kariotype group. Induction response rate is surprisingly high for this setting but we still have high relapse incidence, probably due to the low mobilization rate and the consequent moderately low transplant feasibility. Alternative consolidation regimen, possibly not including Fludarabine, should therefore be explored.