Feasibility of Outpatient High Dose Cytarabine in Patients with Acute Myeloid Leukemia

Background: High dose cytarabine (HiDAC) consolidation in AML is conventionally given in the inpatient setting over approximately 6-7 days. Patients usually tolerate this treatment uneventfully, with occasional cytarabine-related fever or rash. As the demand for limited inpatient healthcare continues to escalate, there is an urgent need to consider transitioning appropriate elective inpatient chemotherapy regimens to the outpatient setting to avoid unnecessary admission and save cost.

The aim of our project was to examine the feasibility, safety and efficacy of outpatient administration of HiDAC in our institutional setting.

Methods: Consecutive adult patients (>18 years old) with AML who fulfilled the inclusion criteria were recruited from our cancer center. All patients received daily HiDAC for 6 consecutive days (Based on ELN 2017 guideline), prophylactic steroid eyedrops and oral anti-emetic for 7 days. A nursing workflow for inpatient and outpatient to facilitate the transition of care. A patient information sheet was also produced to educate the patient and caregiver. Prior to implementation, outpatient training of nursing staff was conducted to ensure familiarity with administration, blood monitoring and common toxicities for the regimen. Prospective outcomes collected included chemotherapy-related toxicities (graded according to CTCAEv4.0), efficacy (continuous complete remission) of outpatient administration, logistics (including cancellations, delays) and number of admission days saved.

Results: Over the period between September 2018 to July 2019, 15 patients were screened for suitability of outpatient HiDAC. 10 were eligible. Of the five ineligible patients, 2 were due to lack of caregiver and the other 3 patients had poor performance status (ECOG 3). 9 patients had at least 1 cycle of outpatient HiDAC. The other patient with single cycle had dose interrupted due to fever and hypotension and was admitted for presumed sepsis. A total of 16 cycles outpatient HiDAC were administered. All except one cycles were completed successfully in the outpatient setting. The adverse events observed during the 6 days treatment were three episodes of cytarabine-related fever, two patients had grade 1 cytarabine-related rash which resolved completely with antihistamine within a week, two patients had Grade 2 vomiting which resolved with additional oral anti-emetics and one with presumed sepsis that require admission. There was no cerebellar toxicity observed during treatment phase. All adverse events were managed in outpatient setting except one case with fever and hypotension resulting in admission. No treatment related mortality associated with the 16 cycles of HiDAC. Median time to neutrophil recovery was 25 days (range: 22-30 days), while median time to platelet count recovery was 32 days (range:21-63 days). All patients remained in complete remission at a median follow-up of 5 months (range: 1-7.5 months). Median time of delay administration was 50 minutes (range: 0-120 mins). 42% of the cycles had delay of <30 minutes. The main causes of delay were due to delay preparation by pharmacist (70%), nursing related (15%) and doctor-related (15%). With an average length of stay of 7 days for inpatient administration of HiDAC, we have saved 112 bed days from this 16 cycles of outpatient HiDAC administration. This would translate into 54% cost saving when compared to inpatient cost.

Conclusions: Our results show outpatient administration of HiDAC is feasible and safe. Importantly this results in a significant number of admission days saved with consequent cost savings for the patient while freeing up bed capacity for necessary admissions. Other intangible benefits would include reduced risk of hospital-acquired infection as well as improved psychosocial well-being of patients and their care-givers. On-going challenges include reducing time of delay, outpatient chemotherapy chair availability and transitioning to fully ambulatory chemotherapy infusion pumps.