Geriatric Assessment Driven Treatment In 149 AML Elderly Patients

In elderly AML the prognosis still remains poor and unchanged in the last decades, with only 10% long term OS. Aging is often synonymous of frailty, traducing in difficulties of enrolment of older patients in experimental study. We explored feasibility and efficacy of an high dose Cytarabine regimen, the so called ‘Memorial’, including Idarubicin plus Amifostine, in a cohort of 149 AML patients older than 59 years and prospectively evaluated by Multidimensional Geriatric Assessment, between 1999 and 2010. We estimated comorbidities by CIRSG, presence of geriatric syndromes and autonomy in daily life activities (ADL) score as described by Balducci et al, frail patients, candidate to best supportive care (BSC), have been identified as those with 1 grade III or more than 2 grade II comorbidities or a geriatric syndrome or ADL score<6. Ninetyone patients (61%) resulted fully fit or partially fit but with adequate cardiac function (50% EF by echocardiography) and therefore eligible to receive a Memorial based induction and consolidation. The 58 patients of the BSC group, compared with intensive chemotherapy group, had a higher incidence of unfavourable karyotype (64.5% vs 40.7%, p= 0.05), secondary AML (53.4% vs 39.6%, p=0.005), WHO PS>1 (44.4% vs 12.1%, p=0.003), age>69 years (82.7% vs 42.9%, p<0.001).

In the 91 patients we observed 5 induction deaths (5.5%) and 76% CR rate (67/88, 3 too early) with 67 grade III-IV febrile episodes, 13% and 9% grade III-IV mucositis and liver toxicity. Neutrophils (>1,500/ml) and platelets (>20,000/ml) recovery was achieved on days +15 and +16 respectively, with a median duration of hospitalization of 30 days (range: 15-69). Sixty-one patients achieving CR received a consolidation, followed by Allogeneic Transplant in 4, Autologous Transplant in 22 and Gemtuzumab Ozogamycin in 23, according to the mobilization results and donor availability. The remaining patients went off the study because of early leukemia recurrence or poor tolerance.

With a median follow-up of 70 months we observed a 20.4% 8 years OS with a median duration of 11.4 months. The 58 BSC patients had a significantly lower OS since all died within 18 months with a median OS of 1.5 months (p<0.001).

The presence of poor risk cytogenetic was confirmed as the only factor significantly predictive of refractory disease with a RR of 3.26 (95% CI: 1.18-9.53) p=0.03. By the way we observed a 63,6% CR rate in this unfavourable setting, unusually high if compared to the results reported by the literature.

Eight years OS was significantly reduced at univariate analysis in patients with secondary disease vs those with de novo AML (10.4% vs 27.1%; p= 0.04); in those with unfavourable cytogenetic risk vs other risk groups (11.4% vs 30.3% p= 0.01) and in those with WBC count> 50,000/ml vs < 50,000/ml (0% at 33 months vs 23.4%, p= 0.009). Multivariate Analysis selected only cytogenetic risk and hyperleukocytosis as predictors of Overall Survival. Patients with poor karyotype had a 2.1 relative risk to die and a 1.89 relative risk to die or relapse when compared with patients with other cytogenetic risk (p=0.005, 0.012), those with hyperleukocytosis ≥50,000/ml showed lower OS and EFS in comparison with patients with a WBC count <50,000/ml, with relative risks respectively of 3.53 and 3.45 (p=0.001).

In conclusion Multidimensional Geriatric assessment allows a reproducible and accurated selection of AML elderly patients eligible for intensive chemotherapy treatment.

Memorial plus Amifostine represents an intriguing approach in elderly AML patients with an acceptable haematological and extra-haematological tolerance, a transplant feasibility comparable to other studies; finally 8 yrs OS doubled than that reported by the literature.