Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia

Abstract

BackgroundThere is a need for standardization of treatment decisions in older patients with acute myeloid leukemia. The aim of the present study was to analyze the decisional value of poor risk factors in 416 elderly patients treated in the ALFA-9803 trial in order to derive a decisional index.

Acute myeloid leukaemia in the elderly: a review

“…More blasts at diagnosis predicted worse outcomes (Baudard et al, 1994), as did CD34-positive disease (Rollig et al, 2010), the presence of chromosomal monosomies (Breems et al, 2008;Medeiros et al, 2010), decreased expression of CD65s (Paietta et al, 2003) and increased expression of CD7 (Stasi et al, 1996). Interestingly, age is not a multivariate predictor of outcomes in several models (Chen et al, 2005;Gupta et al, 2005a;Malfuson et al, 2008), suggesting other risk factors may be more important for treatment decisions. Gene expression profiling in older patients has revealed clusters of patient samples that contain both adverse and favourable cytogenetics (Wilson et al, 2006), suggesting there are important biological prognostic factors that have yet to be discovered.…”

Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

“…Even though restricted to patients under 70 years, most of whom had intermediate-risk cytogenetics, our study population included patients not likely to benefit from intensive therapy according to the decision index our group has proposed, 5 and should instead be candidates for investigational therapies. Restricting our analysis to patients with a favorable decision index, mainly by excluding patients with high-risk cytogenetics, there was still no benefit from a more intensive strategy in terms of either global strategy or of post-remission therapy, as assessed by overall survival and overall survival from complete remission, respectively.…”

“…The decision index was defined according to Malfuson et al 5 As the age criterion of 75 years old or more taken into consideration by this decision index was not relevant to the present cohort, only performance status and white blood cell count criteria were used to define patients with an unfavorable index. Briefly, an unfavorable index was assigned to patients with highrisk cytogenetics and/or the two following factors: a performance status score of 2 or more and a white blood cell count of 50¥10 9 /L or more.…”

“…1 Patients likely to benefit from intensive chemotherapy combining standard doses of cytarabine arabinoside with an anthracycline ("7+3" regimen) can be identified by various scores, [2][3][4] including a proposed decision index derived by our group. 5 Age, cytogenetics, white blood cell count, antecedent hematologic disorders, performance status, and comorbidities are the main factors which are taken into consideration for decision-making. In selected patients, standard intensive induction yields complete remission rates around 50%.…”

Anti-natural Killer Inhibitory Receptors in Elderly Patients with Acute Myeloid Leukaemia

“…5,6 The reasons for such a poor outcome reside in both the patient and the disease; in the patient because ageing is associated with a reduction of functional reserves and an accumulation of co-morbidities, which increases the risk of chemotherapy-related mortality and morbidity and precludes the use of intensive regimens shown to be effective in younger patients. 7,8 AML in the elderly is more frequently associated with poorprognosis features such as unfavourable cytogenetics, 9 antecedent of myelodysplastic syndrome, immature forms expressing CD34 10 or multidrug-resistant gene expression. …”