Mitoxantrone and Etoposide with or without Intermediate-Dose Cytarabine for the Treatment of Patients with Primary Induction Failure or Relapsed Acute Myeloid Leukemia

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AbstractAbstract 2174 Introduction:The prognosis for patients with primary induction failure (PIF) or relapsed acute myeloid (Rel-AML) is poor. Mitoxantrone (M) plus etoposide (E)- based salvage regimens (ME), in particular, either alone or with intermediate dose cytarabine (MEC) are effective in these high risk patients; However, these regimens have not been directly compared. Heterogeneity in chemotherapy dose, dose escalation and age have been important limitations in the evaluation of previous studies. Also problematic, historically patients were classified according to FAB criteria. Since then, karyotype has been shown to be a main determinant of prognosis. The influence of karyotype on response to ME or MEC is currently unknown. Herein, we report the response to treatment with a fixed dosing schedule of ME or MEC in 66 patients treated for PIF or Rel-AML with intermediate(intermed-) or unfavorable(unfav-) risk cytogenetics. Differences in CR between ME and MEC subsets were analyzed to determine the effect of adding of C to ME. Methods:66 consecutive patients with PIF or Rel-AML treated with either ME(n=37)or MEC(n=29) between 10/2004-12/2008 were evaluated. All patients had received initial induction therapy with daunorubicin 45–60mg/m2 IV bolus d1-3 and cytarabine 100mg/m2 CI d1-7(7+3), and consolidation with HIDAC if CR was achieved. ME and MEC were dosed according to previously published studies. The decision to use a given salvage was left to the discretion of the treating physician. Chi-Square test was used for statistical analysis. Results:Table1 shows there was no difference between the ME and MEC groups with regards to age, sex, % blasts at initial diagnosis, and %CR after initial induction with 7+3, or % patients who received inter- to high dose C prior to ME or MEC. Length of CR (after 7+ 3 and consolidation) was significantly longer in the MEC group. A significantly higher number of CR's was observed in the MEC group compared to ME(p=0.05). Within the MEC group, no difference in CR was observed between patients with intermed- and unfav-risk cytogenetics(p=0.96). The same was true within the ME group(p=0.13). When MEC was compared to ME, a significant difference in CR was observed in patients with unfav-risk cytogenetics(p=0.044) and patients <60years old. Prior to therapy, MEC patients had higher number of blasts. MEC patients had a significantly longer duration of remission. One patient in both the ME and MEC group died before hematopoetic reconstitution. Conclusion:In clinical practice, as observed in the present study, we observed a greater overall CR rate in patients who received MEC compared to those treated with ME, particularly in younger patients with unfav-risk cytogenetics. For those who achieved CR after MEC or ME, a longer duration of CR was observed in the MEC group compared to ME. These results could be particularly beneficial for those patients receiving salvage therapy as a temporizing measure prior to allogeneic hematopoetic stem cell transplant ion, and encourages confirmation from a prospective trial.Table 12937Male:Female13/1623/13NSAge(yr/range)54 (21–77)58 (24–79)NS>60yr10/2914/370.8Complete Remission after 1st induction(%)20 (69)27 (75)0.78Number of Chemotx regimens prior to ME/MECn=28150.2n=3280.16n=4140.36Prior treatment with intermediate or high dose Cytarabine24/2934/370.285TreatmentCytogenetics (n=MEC=28:ME=34)*Favorable(respnse,%)1/1 (100)1/1 (100)1Intermediate9/16 (56)7/22 (32)0.13Unfavorable7/11 (64)2/10 (20)0.044Age<6012/19 (63)6/21 (29)0.028Intermediate cytogenetics5/10 (50)3/16 (19)0.19Unfavorable cytogenetics6/8 (75)1/2 (33)0.49Age>605/10 (50)3/16 (19)0.99Intermediate cytogenetics4/6 (66)4/6 (66)1Unfavorable cytogenetics1/2 (50)1/7 (14)0.99Complete remission(%)17 (58)12 (33)0.049Time to relapse(months)2.5 (1–14)1.5 (1–33)0.049Table 2Kaplan-Meier survival percentages from diagnosis to last follow-upKaplan-Meier survival percentages from MEC/ME to last follow-up6m94%55%1 year71%31%2 years42%22%3 years19%18%5 years12%no follow-up beyond 5 years from MEC/ME7 years8%no follow-up beyond 5 years from MEC/ME Disclosures:No relevant conflicts of interest to declare.