Effectiveness of a Strategy to Proceed to Allogeneic Stem Cell Transplantation in All Elderly AML Patients Treated with Intensive Chemotherapy: Only Patients in Complete Remission After First Induction Show Long Term Survival.

Acute myeloid leukemia (AML) in patients over 60 years has a poor prognosis with 2-year survival rates of less than 10%. Intensive chemotherapy improves interim survival but not long term cure rates compared to non-intensive care. Allogeneic stem cell transplantation (alloSCT) has the potential to cure elderly AML patients, but most reported studies refer to selected patient cohorts. We have developed a T cell-depleted reduced intensity conditioning (RIC) regimen and preplanned post alloSCT donor T-cell infusion, inducing only limited GVHD directly after alloSCT (von dem Borne et al. Curr Opin Oncol 2009) making it a suitable regimen for elderly patients. In 2006, we instituted a center policy to perform RIC alloSCT in every newly diagnosed AML and high grade MDS patient >60 years who qualified for induction therapy. We here report feasibility, toxicity, and outcomes of this strategy.

From 2006 to 2011, 45 consecutive patients aged 60–79 years (median: 67) with newly diagnosed AML (n=43) or high-risk MDS (IPSS score >1.5) started induction chemotherapy (continuous infusional cytarabine combined with bolus anthracycline with or without etoposide). Patient not achieving complete remission (CR) after induction received a re-induction cycle with high-dose cytarabine with or without amsacrine. Patients in CR after induction or re-induction were to receive one cycle of consolidation chemotherapy, followed by RIC alloSCT in case of continuous CR.

Six patients (13%) died during first induction. 19 patients (43%) achieved CR after first induction, of which 12 received a RIC alloSCT (27% of intention-to-treat population) after consolidation chemotherapy. Causes why CR patients did not receive alloSCT were good-risk AML (n=1), early relapse after consolidation chemotherapy (n=2), high age (patient had become over 80 years) (n=1), infectious complication (n=1) and patient choice (n=2).

20 patients (45%) failed to achieve a CR after induction chemotherapy. 16 of these patients received the planned re-induction therapy; 10 of these patients achieved a CR, 7 patients received a third chemotherapy course for consolidation, and 4 underwent RIC alloSCT. There were no long-term survivors in this group. 19 patients without CR after 1st induction died from progressive AML.15 AML deaths after 1st induction failure occurred in patients who were treated according to the institutional strategy (6 patients with progressive disease despite additional chemotherapy, 1 relapse prior to start of re-induction, 3 relapses early after consolidation, and 4 relapses after alloSCT). Relapses in patients not adhering to the pre-specified strategy occurred in patients opting to discontinue therapy while in CR (n=3), inability to find a donor (n=1), and complication preventing alloSCT (n=1). One transplanted patient died from GVHD.

For the entire intent-to-treat population, the Kaplan-Meier estimate for overall survival at 1 and 2 years after start of treatment is 38% and 19%, respectively. For patients achieving CR after 1st induction and receiving alloSCT, Kaplan-Meier estimate overall survival at 2 years after start of treatment is 50%. The main reasons for dying when adhering to the protocol were early death (13%) and refractory/relapsing malignancy (47%). Only 2 patients (4%) died after 1st induction as a consequence of TRM. Non-TRM reasons for not adhering to the protocol with subsequent death due to AML were patient preference (n=4; 9%) and inability to identify a matched donor (n=1; 2%).

This single-center comprehensive cohort study shows that 38% of elderly AML patients that are deemed fit for induction chemotherapy can be brought to alloSCT in CR. At diagnosis, this strategy offers a chance of cure for about 20% of patients. Fifty percent of patients achieving CR after 1st induction and receiving alloSCT are alive 2 years after alloSCT. Since none of the patients who failed to achieve a CR after 1st induction survived long-term, the most important aspect to improve this strategy is to strive for higher primary CR rates, including the prevention of early deaths. Alternative strategies, such as combining alloSCT and consolidation chemotherapy into one coherent regimen may especially improve outcome by preventing early relapse and improving patient compliance. Post-induction TRM and lack of a donor were only minor obstacles to this potentially curative approach.

No relevant conflicts of interest to declare.