Primary end points -evaluation of safety in terms of: TRD; severe hematological and extrahematological toxicity -evaluation of CR rate. Secondary end points 1-days of hospitalization during induction therapy; 2-percentage of patients suitable for PBSC collection and ASCT 3-OS and LFS

PBSC Collect INDUCTION PHASE* d 1 d 2 d 3 d 4 ARA-C* 3 g/mq IDA* 40 mg/mq Amifostine d 5 IDA 30 mg/mq Amifostina CONSOLIDATION PHASE ARA-C 3 g/mq ARA-C 3 g/mq ARA-C 3 g/mq ARA-C 3 g/mq PBSC Collect d 1 d 2 d 3 d 3 d 4 *IN PTS > 70 yrs ARA-C and Ida doses have been reduced by 30%.

15 pts >3 x 106 PBPC collected 14 pts ALTERNATIVE THERAPY 42 patients Amifostine+IDA+ARA-C 10 NR 1 ED 29 CR 2 PR 3 CR (II line) ORR 31/41 (76%), with II line 34/41 (83%) 2 RELAPSE 32 CONSOLIDATION COURSE 2 TRD 29 CCR evaluable for collection 1 RELAPSE 15 pts >3 x 106 PBPC collected 14 pts ALTERNATIVE THERAPY 1 RELAPSE RESULTS After the first induction course 29 patients achieved CR and 2 PR; 10 patients were NR, but 3 of them, who attained a significant blast clearence in the bone marrow, achieved CR after the second induction course of chemotherapy; we observed one only TRD (2.3%). The final ORR was 83% with a CR rate of …. Before starting the consolidation therapy we observed 2 relapses, so 32 out of the 34 patients achieving CR received the consolidation therapy which was based on the association of ARA-C intermediate dose plus Lyposomal Doxorubicin in .. Cases and the same schedule of IDA-Amifostine plus HD-ARA-C in the other……. We observed 2 TRD during the consolidation therapy (4…%) and 29 patients maintained CR and were evaluable for the PBPC collection. 15 patients were able to collect>3x10e6CD34+cells/Kg while 14 failed to mobilize a sufficient number of CD34+ cells; 1 patient relapsed very quikly after collecting more than …CD34+ cell; consequently only 14 patients could be autotransplanted with TBI-free conditioning regimens including HDM. The 14 patients who could not be autotransplanted received a second attempt of mobilising chemotherapy, without attaining a relevant CD 34+ cell peak and were followed without any further therapy in .. Cases or received low dose Gemtozumab in .. Cases. We observed 3 TRD in the 14 patients autotransplanted while the remaining 11 patients showed a promp and complete engraftment. Overally 9 patients are in first complete remission with a median follow-up of … (range ….) with a median LFS of …. The OS was and …. 14 PBSC AUTOTRANSPLANT 3 TRM 1 DEC (in CR) 11 EVALUABLE 3 CCR 6 CCR

we did not observe a superior OS in those patients …….Intriguingly, we did not observe a superior OS in those patients who received consolidation with ASCT, compared with those who received another consolidation (???) due to an insufficient PBSC mobilization………….

The second part of history….. 123 patients with non-M3 AML, median age 71 years (range 55-89), were observed in our institution. All patients were preliminary evaluated according to a simplified MGA so we were able to separate fit patients from unfit or frail patients. 79 fit patients were enrolled in this protocol 27 (35%) had AML secondary to MDS Clinica di Ematologia-Università Politecnica delle Marche

Prospective study: design CR after intensive induction with Memorial-Amifostine Consolidation CHT with HD-ARAC-Ida-Amif Sufficient PBSC harvest (Cd34+>3,5x10e6/kg) YES NO ASCT MYLOTARG 5 mgx3/4 wks

Clinica di Ematologia-Università Politecnica delle Marche LOW DOSE Gentuzumab Ozogamicin, after intensive induction in older AML patients: results in 13 patients in a single centre institution Poloni A, Trappolini S, Costantini B, Capelli D, Troiani E, Mancini G, Discepoli G, Montanari M, Gini G, Scortechini I, Leoni P and Olivieri A Rationale: low dose GO as post-remission approach after CR, in order to eliminate the minimal residual disease in elderly patients enrolled in a pilot prospective study Clinica di Ematologia-Università Politecnica delle Marche

Clinica di Ematologia-Università Politecnica delle Marche 78 elderly AML patients, eligible for aggressive chemotherapy: 57 (73%) achieved CR .....among these 48 (84%) received first consolidation with intensive chemotherapy and were planned to receive a further consolidation with ASCT or low dose GO in case of PBSC collection failure: ......21 patients successfully achieved PBSC collection and 19 undergo ASCT: in this subset we observed 4 TRD (21%) with 9 patients relapsing and 6 patients still alive in CR with a median follow-up of 60 months (range, 7-100). Therteen patients, that failed PBSC mobilization, have been furtherly consolidated with GO at the dose of 3 mg/m2 for three times, monthly, with a median follow-up was 23 months (range, 6-62) Clinica di Ematologia-Università Politecnica delle Marche

Dopo terapia d’Induzione, 57 (72,1%) dei 79 pazienti hanno raggiunto la remissione completa Strategia terapeutica nei 42 pazienti in RC continuativa dopo 1° consolidamento

Overall Survival stratificata per tipo di terapia Tutte le sopravvivenze sono state considerate dalla fine del I° consolidamento e non sono stati considerati gli allotrapianti

Disease Free Survival stratificata per tipo di terapia

CARATTERISTICHE DEI 13 PAZIENTI SOTTOPOSTI A TERAPIA CON MYLOTARG   Sesso Iperleucocitosi Malattia secondaria Cariotipo Età Status Pz 1 M NO intermedio <70 Vivo RC Pz 2 >70 Vivo Relapse Pz 3 >10000 non valutabile Morto Pz 4 F favorevole Pz 5 SI Pz 6 Non valutabile Pz 7 Pz 8 Pz 9 Non favorevole Pz 10 Pz 11 Pz 12 Pz 13

TOSSICITA’ MYLOTARG Tossicità di grado III/IV (secondo WHO): - 9 casi di tossicità ematologica - 1 caso di ipertransaminasemia - 3 reazioni di tipo allergico - non si sono osservati eventi avversi maggiori Dei 13 pazienti 2 sono ricaduti e deceduti rispettivamente dopo 11 e 19 mesi dall’ultima infusione di Gemtuzumab-Ozogamicin; un paziente è ricaduto dopo 20 mesi ed ha ottenuto una seconda remissione completa con un ciclo chemioterapico di reinduzione; un altro paziente, ricaduto dopo 32 mesi, ha ricevuto una altro ciclo di consolidamento con GO dopo una seconda remissione completa mantenuta per circa 12 mesi. Quindi 10 pazienti sono vivi e attualmente in remissione completa.

Proposal