Abstract
Elderly patients (EP) of 60 years and above with acute lymphoblastic leukemia (ALL) have a dismal prognosis, but pediatric-inspired chemotherapy and allogeneic stem cell transplantation (allo HCT) are used reluctantly due to limited data and historical reports of high treatment-related mortality in EP. We analyzed 130 adult ALL patients treated at our center between 2009 and 2019, of which 26 were EP (range 60–76 years). Induction with pediatric-inspired protocols was feasible in 65.2% of EP and resulted in complete remission in 86.7% compared to 88.0% in younger patients (YP) of less than 60 years. Early death occurred in 6.7% of EP. Three-year overall survival (OS) for Ph − B-ALL was significantly worse for EP (n = 16) than YP (n = 64) with 30.0% vs 78.1% (p ≤ 0.001). Forty-nine patients received allo HCT including 8 EP, for which improved 3-year OS of 87.5% was observed, whereas EP without allo HCT died after a median of 9.5 months. In Ph + B-ALL, 3-year OS did not differ between EP (60.0%, n = 7) and YP (70.8%, n = 19). Non-relapse mortality and infection rate were low in EP (14.3% and 12.5%, respectively). Our data indicate that selected EP can be treated effectively and safely with pediatric regimens and might benefit from intensified therapy including allo HCT.
Highlights
In acute lymphoblastic leukemia (ALL), cure rates as high as 90% are reported in pediatric patients [1]
T-ALL was less common in elderly patients (EP) than younger patients (YP) (3/26, 11.5% vs 21/104, 20.2%; p = 0.308), whereas incidence of Philadelphia chromosome (Ph)-positive ALL was higher compared to YP (7/26, 26.9% in EP vs 19/104, 18.3% in YP, p = 0.374)
General risk stratification showed no significant difference between the age groups, but the overall comorbidity rate in EP was high with 84.6% and significantly more cardiovascular (69.2% vs 14.4%, p = 0.007) and metabolic (50.0% vs 16.3%, p ≤ 0.001) comorbidities as well as prior malignancies (42.3% vs 15.4%, p = 0.002) compared to YP
Summary
In acute lymphoblastic leukemia (ALL), cure rates as high as 90% are reported in pediatric patients [1]. With the adoption of pediatric-inspired treatment regimens into adult ALL therapy and a better understanding of the oncogenic landscape with refined risk classification, improved response rates and outcomes especially in Philadelphia chromosome (Ph)-positive ALL have been achieved in recent decades. High-risk genetic alterations, which can contribute to resistance to conventional chemotherapies, are more frequent with increasing age. Treatmentrelated toxicity of pediatric-inspired chemotherapies with historically reported mortality rates of up to 42% in older patients has led to a conservative use of pediatric-inspired treatments in this patient group [4, 6,7,8,9,10,11]. Allo HCT was restricted to younger patients (YP) because of concerns about high transplant-related mortality (TRM) in patients older than 60 years. It could be shown that outcome can be improved in EP with survival rates of 18 to 48% and TRM rates of 21 to 41% when reduced-intensity conditioning
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