Does the Number of Cycles of Consolidative High Dose Cytarabine for Patients with AML Undergoing Allogeneic HSCT Matter? a Single Center Experience

Introduction High-dose cytarabine (HD-AraC) is an important component of intensive post-remission therapy for acute myeloid leukemia (AML). Its efficacy in core-binding factor (CBF) AML has been well established but it remains controversial whether HD-AraC is effective before allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Herein, we report our experience at Allegheny Health Network (AHN) regarding the number of cycles of HD-AraC used before Allo-HSCT and its effect on survival. Methods We retrospectively analyzed 49 patients with AML who received HD-AraC after achieving complete remission and underwent Allo-HSCT at our institution between January 2010 and June 2018. Patients with acute promyelocytic leukemia (APL), CBF-AML, and primary induction failure were excluded. The HD-AraC dosing regimen used at our institution is 3,000 mg/m2 IV every 12 hours on days 1, 3, 5 for a total of 6 doses per 28-day cycle. Fifteen patients received 1 cycle, twenty patients received 2 cycles, and fourteen patients received u003e2 cycles of HD-AraC. The majority of the patients (n=32, 65%) received a myeloablative conditioning (MAC) regimen. The unadjusted probabilities of overall survival (OS) were estimated using Kaplan-Meier method and a multivariate analysis was performed using multiple logistic regression model for odds ratio, 95% confidence interval, and p-value. Number of HD-AraC cycles, age, conditioning regimen, and AML risk stratification per European Leukemia Net (ELN) were used as covariates. Results Median age was 56 years (IQR: 45.1-63.3) and median days to Allo-HSCT was 155 (IQR: 127-202). Our patients received a median of 2 cycles (IQR: 1-3) of HD-AraC before Allo-HSCT. With median follow up of 10 months, the median overall survival for patients who received 1, 2, and u003e2 cycles of HD-AraC was 9.9, not reached, and 33 months, respectively. Patients who received 2 cycles of HD-AraC showed a trend toward lower mortality with odds ratio of 0.22 (95% CI: 0.03-1.79, p-value 0.158). Conclusion Our data shows that patients who received two cycles of HD-AraC had a lower mortality rate with a trend towards significance. However, the majority of these patients also received a MAC regimen (n=18, 90%) which is significantly (p-value 0.005) more than patients who received 1 cycle (MAC n=6, 40%) and u003e2 cycles (MAC n=8, 57.1%) of HD-AraC. In addition to this bias that is related to the retrospective nature of the study, the small sample size as well as this being a single center experience limits definitive conclusions. Larger studies are needed to determine the optimal number of HD-AraC as a bridge to Allo-HSCT.