Time from Hospital Admission to Induction Chemotherapy Adversely Affects Outcomes in Patients with Acute Myeloid Leukemia

Abstract

Background: The duration of time from the diagnosis of acute myeloid leukemia (AML) to the initiation of chemotherapy is dependent on multiple factors. Previous studies suggest that delays in the time from diagnosis to treatment do not impact overall survival (OS) and complete remission (CR). As a result, awaiting laboratory analysis of molecular targets for therapy, specifically FLT3, has become more commonly adopted by clinicians. However, this strategy can lead to significant delays in initiation of chemotherapy. The aim of this study is to analyze the impact of delaying chemotherapy on OS and CR in AML patients. Methods: We performed a retrospective analysis on adult patients with AML who were treated with induction chemotherapy at The University of Oklahoma Health Sciences Center from January 2000 to June 2012. Time from admission to treatment (TAT) was calculated from the date of admission to the date of initiation of chemotherapy. In addition, we analyzed the admission day of the week and its association with TAT (days). Association between CR and TAT was assessed using ANOVA and Chi-Square tests. Kaplan-Meier estimates of median OS were calculated for groups defined by categorical variables. A Cox Proportional Hazards model on OS was implemented using TAT, age, risk status (favorable, intermediate and unfavorable risks), day of admission, distance to hospital, and white blood cell (WBC) count. Interaction was assessed and a backward selection procedure was used to find the covariates associated with OS. Statistical analysis was performed using SAS 9.3 software. Results: A total of 160 patients with AML received induction chemotherapy at our institution during the defined time, with 137 meeting inclusion criteria. The median age at diagnosis was 51 years with 63.7% being male and 36.3% being female. Of these patients, 77.0% were white, 10.6% African American, 6.2% Native American and 3.7% Hispanic. The median TAT for all patients was 3.0 days. There were 116 (84.7%) patients treated within 0-4 days (Group 1) and 21 (15.3%) patients treated beyond 4 days (Group 2). Patients in Group 1 had a median survival of 252.5 days compared to those in Group 2 of 188.5 days (p = 0.0958) when analyzed univariately. Multivariable analysis demonstrated TAT of 0-4 days was independently related to OS with a hazard ratio of .604 (95% CI 0.369-0.990, p = 0.0451). The CR rate for Group 1 was 69.8% compared to Group 2 of 54.6% (p = 0.0692). In addition, patients admitted on a weekday (Monday-Friday) were more likely to initiate chemotherapy within 0-4 days as compared to patients admitted on the weekend (Saturday-Sunday) with a p = 0.0102. Conclusion: AML patients treated more than 4 days following admission have decreased OS and a trend toward decreased rate of CR as compared to patients treated within 0-4 days. This finding is independent of age, risk status, WBC count, and distance to hospital. Also, patients admitted on the weekend were more likely to experience delays in initiating chemotherapy compared to those admitted on the weekday. Although a larger sample size and testing in other clinic settings needs to be done to confirm this relationship, this study suggests treating AML patients within 4 days of hospital admission may be associated with improved outcomes. Disclosures No relevant conflicts of interest to declare.

Systematic review and meta‐analysis: Prognostic impact of time from diagnosis to treatment in patients with acute myeloid leukemia

“…Six studies were included in the meta-analysis. 3,[5][6][7][8][9] The logarithmic transformed (log) OR of CRs and the standard error (SE) of log ORs were considered as the effect size. The extracted data for each study included the study author, year, TDT range in days, and total number of subjects and total number of CRs at each TDT level.…”

“…Six studies were included in the meta‐analysis 3,5–9 . The logarithmic transformed (log) OR of CRs and the standard error (SE) of log ORs were considered as the effect size.…”

“…Kamoda et al -2981 five of the six studies included in the meta-analysis, although only two of these studies reached statistical significance. 3,5,[7][8][9] Metaanalysis revealed that the pooled OR of CR based on all unadjusted ORs was 0.974 (95% CI, 0.958-0.990; p = .0016), which means that each 1-day increase in TDT was significantly associated with a 2.6% decrease in the risk of CR. Additionally, there was significant heterogeneity between studies (I 2 = 59.68%; Q = 11.7684; p = .0381).…”

“…Conversely, two studies found that a delay in treatment of >4 days was associated with worse OS, regardless of age. 8,19 Juliusson et al 7 found that a TDT of >5 days was associated with significantly decreased 2-year survival. However, after stratification by age, results no longer met statistical significance in either age cohort.…”

“…7 The remaining six studies did not find a significant association between TDT and CR rate. 5,6,8,9,17,19 See Table 7.…”