Historically, treatment of AML has focused on intensive high dose comibination chemotherapy. Since AML is frequently diagnosed at an advanced age there is often concern that the morbidity of treatment outweighs benefit. In the province of Manitoba all patients with AML are referred and care is coordinated at one regional center. Through linkage of the provincial cancer registry and the clinical records at CancerCare Manitoba and the Manitoba Blood and Marrow Transplant Program a historical cohort of adults with newly diagnosed AML in Manitoba between 2001 and 2006 was assembled with complete treatment records and outcomes.
During the 5 year period 185 adult patients were diagnosed with AML (median age at diagnosis 69y (range 17-96ys) with an age-adjusted incidence of 2.66 per 105. Remission Induction chemotherapy was generally offered to fit adult patients up to 80 years of age. The proportion of patients 60-80 ys at diagnosis who underwent conventional remission induction therapy was less than those <60 years old at diagnosis (24% (31/127) vs 76% (44/58)). While younger patients (<60y) were likely to enter CR 28/44 (64%) and had overall 3 y DFS of 35% this was frequently in the setting of allogeneic transplant (12 underwent HSCT in CR1 and 8 underwent HSCT in ≥ CR2). During this time period allogeneic transplantation was not offered for pts >60 y.
For patients between 60-80 ys, receiving conventional induction therapy followed by HDAraC consolidation, 19/31 (61%) entered remission. There was a survival benefit (p<0.0001, Log Rank) as against supportive care. The decision to treat was made on a clinical assessment of ability to tolerate intensive chemotherapy but on analysis there was no difference in age, Karnofsky score or pretreatment WBC in those receiving treatment and not. The beneficial effect of induction therapy on OS remained significant (HR 2.367 95% CI 1.226 to 4.667, p=0.01) when adjusted for pre-treatment WBC, Karnofsky performance score and age. The magnitude of response was less than that seen with the younger cohort in that the median length of survival was 12 mo (range 6-26 mo) with no long term survivors. Cause of death in those entering remission was related to disease relapse in the majority of cases.
In this population-based analysis, patients with AML ≥ 60 years have a modest survival benefit from conventional AML induction and consolidation. This needs to be tempered with the morbidity of treatment. Since allogeneic transplant is such an important tool in younger patients possible introduction of submyeloablative transplantation in those older adults entering CR may be appropriate. For the majority of older patients newer therapies that are better tolerated need to be explored.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.