Evaluation of Prognostic Factors after Induction Chemotherapy for Acute Myeloid Leukemia

Purpose: Recent studies have shown that dose escalation of daunorubicin from 45mg/m2 to 90mg/m2 during acute myeloid leukemia (AML) induction showed response benefit and overall survival in patients <=65 years. Yet, the further management of patients with persistent disease based on the evaluation of D14 bone marrow has often been questioned due to lack of data. The primary purpose of this study is to evaluate the overall remission rates of patients with a positive D14 bone marrow compared with those who had a negative D14 results, and to determine if blast % on the D14 bone marrow aspirate is a prognostic indicator for remission and survival in acute leukemia patients who underwent induction chemotherapy. We aim to investigate the relevance of the D14 bone marrow result by dividing the result into blast percent categories and investigate if the there is a correlation between D14 blast % and CR.

Patients/Methods: This was an IRB approved retrospective chart review conducted at North Shore University Hospital. Adult patients with AML who received standard induction 7 + 3 Daunorubicin and Cytarabine from 2010 to 2015 were included. 150 patients were reviewed and those that were eligible were evaluated for various factors (D14 blast %, initial marrow blast %, gender, age, cytogenetic risk profile, initial WBC, initial hemoglobin, initial platelets and initial LDH levels, along with those lab values at D14) for tests of association with CR. These patients' D14 blast % biopsies were divided into blast percent categories as followed: (Chemotherapeutic/<1%, 1-10%, 10-30%, 30-60% and > 60%). Complete remission (CR) was defined as patients having <5% blasts on their day 28 bone marrow or day 63 and corresponding neutrophil count >1,000 and platelet count >100 k. Fisher's exact test was used to compare the proportion of patients who reached CR among the D14 blast % categories, and on other categorical data. The Wilcoxon test was utilized to compare CR on continuous variables. Results were considered statistically significant if p < 0.05.

Results: 115 patients were analyzed and we found no significant association between D14 blast % and CR status. However, initial blast % was found to be significantly associated with CR status (p=0.009), specifically, those with >60% initially had the greatest CR rate. D14 hemoglobin, D14 platelets or D14 LDH levels were not significantly associated with CR status (p=0.67, p=0.33, and p=0.13, respectively). Similarly, initial WBC, hemoglobin, platelets and LDH levels were each not significantly associated with CR (p=0.99, p=0.51, p=0.47 and p=0.36, respectively). Results did provide evidence to suggest that D14 WBC was significantly associated with CR (p=0.02), but when both D14 WBC and initial blasts % were included in a multiple logistic model, WBC was no longer a significant predictor of outcome. As such, only initial blast percent (at time of diagnosis or initial visit) was deemed predictive of CR response day at D63 (p=0.0142); patients with initial blast >60% had the greatest rate of CR compared with <20% blasts initially.

Conclusion: The data suggests that there is no statistical difference between the blast % on the D14 bone marrow and the achievement of CR during induction chemotherapy for AML. Secondary outcomes showed that the initial blast % was associated with CR especially in patients with an initial blast % >60%. Also, D14 WBC might be associated with remission. Prospective studies are required to confirm these findings.