Does Time Matter from Diagnosis to Induction in Acute Myeloid Leukemia?

Introduction:

Acute myeloid leukemia (AML) is considered an aggressive hematological malignancy. While molecular and cytogenetic testing may change prognosis and guide treatment intensity, timing from diagnosis to treatment (TDT) on the other hand may impact treatment outcomes and survival in AML patients. These considerations are sometimes at odds with each other given that molecular results can take up to two weeks to result. We performed a retrospective analysis to assess outcomes in relation to the timing of treatment initiation and in relation to ELN risk stratification.

Methods:

A retrospective analysis was performed on a cohort of AML patients treated at Upstate Medical University Hospital between January 2010 to June 2024. The subjects were at least 18 years old and diagnosed with AML. Patients with APML and those who did not receive any treatment were excluded from the study. We examined the effect of TDT on complete remission (CR) and overall survival (OS). TDT was divided into 3 categories: chemotherapy induction within days 1-5, 6-10, and 11+. Based on European LeukemiaNet (ELN) risk stratification system, patients were classified into 3 risk categories: favorable, intermediate, or adverse. Statistical analysis system (SAS) software, version 9.4 was used for data analysis. Kaplan Meier curves with a chi-square for statistical significance was utilized.

Results:

198 patients were included. 33% (n=66) were younger than age 60, 51% (n=102) were males and 83% (n=166) were white. Patients were classified as 18% (n=36) favorable, 35% (n=69) intermediate, and 42% (n=84) adverse risk. 68% (n=136) had de novo AML. Intensive chemotherapy was administered to 57% (n=112), and non-intensive chemotherapy to 43% (n=86). Chemotherapy induction began for 62% (n=124) on days 1-5, 14% (n=28) between days 6-10, and 11% (n=22) on day 11 or after. Predicted remission status using time to induction on a logistic regression model showed statistical significance [Χ²(2) = 6.440; p = .040]. The probability of achieving complete remission decreases for those who had induction 11+ days from diagnosis compared to those who had induction 1 to 5 days from diagnosis. This relationship is statistically significant (OR=0.32, 95% CI, 0.125 – 0.796; p=.003). In addition, an induction time of 1 to 5 days decreased the risk of death compared to an induction time of 11 days or more, which was also statistically significant (HR=0.567, 95% CI 0.325 – 0.989). When stratifying for age <60 and ≥60, chemotherapy intensity, and ELN risk stratification, there was no significant difference in CR or OS between TDT groups, except for ELN within TDT 1-5 days our model suggests that patients with favorable risk have a decreased risk of death compared to patients with intermediate risk (HR=0.257, 95% CI 0.088 – 0.751), and patients with adverse risk (HR=0.130, 95% CI 0.045 – 0.374). In addition, patients with intermediate risk have a decreased risk of death compared to those with adverse risk (HR=0.505, 95% CI 0.291 – 0.875).

Conclusion:

Our study results showed improved CR and OS in AML patients who were treated within 1-5 days, compared to 11+ days regardless of age or chemotherapy intensity. When stratified by ELN risk groups, statistical significance for OS was found with TDT 1-5 days in all risk groups. These results suggest that initiating treatment within 5 days of diagnosis correlates with better remission and survival. With the availability of newer therapies, AML treatment recommendations are increasingly based on molecular profiling, highlighting the importance of having these results within a week of diagnosis.