Outcome of Acute Myeloid Leukemia (AML) Induction Therapy Based on D14 Marrow Biopsy According to European Leukemia Net (ELN) Risk Classification
Authors: Ray David , Koprivnikar Jamie L. , McCloskey James K. , Stanislaus Genique , Howlett Christina , Davidow Amy , Depadova Samantha , Goldberg Stuart L. , Faderl Stefan 
Published: October 2019

Abstract
OBJECTIVE: According to standard protocol, the earliest post treatment marker of response following intensive induction therapy in patients with AML is a D14 marrow biopsy. Some controversy has surrounded this practice. This study aims to evaluate response to induction therapy based on D14 marrow assessment meeting genetic risk classifications as defined by the ELN.
METHODS: In a single center, retrospective chart analysis subjects diagnosed with AML treated with 7+3 therapy were included if they had molecular and cytogenetic testing performed at baseline, day 14, and day 28. Baseline characteristics and treatment results at these time points were extracted. Sample demographics and treatment were described descriptively. Risk ratios were calculated to investigate the likelihood of achieving a chemo-ablated[1] bone marrow biopsy at Day 14 across the ELN risk classifications. All analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC).
RESULTS: One hundred thirty eight pts were included. The median age at diagnosis was 57 years (range 26 to 69). The median white blood cell count at diagnosis was 12,800 (range 0.1 to 122,000 per microliter). 6.5% of the pts had secondary AML and 8.7% had AML arising from an antecedent hematologic disorder. ELN risk classifications at diagnosis were 47.1%, 8.7%, 20.3% and 23.9% for favorable, intermediate-I, intermediate-II and adverse, respectively. Demographic variables and baseline characteristics did not differ across risk groups. The percentage of pts achieving a chemo-ablated marrow biopsy at Day 14 was 88%, 83%, 68% and 67% for the Favorable, Intermediate-I, Intermediate-II and Adverse group, respectively (Table 1, p=0.0385). Similarly, the percentage of patients achieving CR at Day 28 was highest for patients with a favorable ELN risk classification (92%) compared to intermediate-I (83%), intermediate-II (71%) and adverse (79%) (Table 2, p=0.0440). Re-induction rate was significantly different when stratified across ELN risk groups (p=0.0487). Risk ratio analysis showed a 26% increased likelihood of achieving a chemo-ablated marrow biopsy when comparing Favorable ELN risk pts to those to those in the non-favorable ELN risk group (RR:1.2552; 95% CI: 1.0526-1.468). A test of discordance comparing hypocellular/hypercellular results based on the Day 14 marrow biopsy with having CR/non CR at end of cycle 1 were not significant across the ELN risk classifications.
CONCLUSION: With the advent of personalized therapy comes the potential to customize treatment and hope to optimize pt outcomes. Our results indicate that karyotype and a range of genetic mutations predict marrow morphology at Day 14. How these results predict long-term outcome needs to be further explored.
[1] (defined as cellularity <10% and residual blasts <5%)

Disclosures
Ray: Ipsen Biopharmaceuticals: Employment. Koprivnikar:Alexion: Consultancy, Speakers Bureau. McCloskey:Amgen: Speakers Bureau; Ariad: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Incyte: Consultancy. Stanislaus:Novartis: Consultancy, Speakers Bureau. Howlett:Pfizer: Honoraria; Sandoz: Honoraria; Teva: Speakers Bureau; Amgen: Honoraria; Eisai: Honoraria. Depadova:Amgen: Speakers Bureau. Goldberg:Novartis: Consultancy; Pfizer: Honoraria; Bristol Myers Squibb, Novartis: Speakers Bureau; Neostem: Equity Ownership; COTA Inc: Employment.