Safety, Feasibility, and Cost-Effectiveness with Outpatient Administration of High-Dose Cytarabine Consolidation in Acute Myeloid Leukemia

Introduction: High-dose cytarabine (HiDAC) consolidation chemotherapy is frequently used in acute myeloid leukemia (AML) patients less than 60 years of age. Traditionally, the potential risk for neurotoxicity, which has been reported to occur in 8–26% of patients, has limited its administration to the inpatient setting with a median length of stay of 5 days. Institutional retrospective data revealed the incidence to be much lower than previously reported with grade III/IV neurotoxicity in only 0.7% of cycles (N=267). As a result, we developed a comprehensive outpatient (OP) approach for the administration of HiDAC utilizing a pre-printed order and monitoring forms, pre-defined eligibility criteria/risk factors, administration/screening checklist, standard ancillary medications, designated scheduling, patient counseling, and written instructions for follow up. The benefits of OP administration may include improved patient satisfaction and decreased institutional costs and constraints on inpatient resources. However, there does not appear to be any published literature to date describing the OP administration of HiDAC. We report herein on the safety, feasibility, and outcomes of 43 patients receiving HiDAC consolidation therapy (n=88 cycles) between September 2006 and July 2008.

Methods: Patients < 60 yo received 3 g/m² over 1 hour every 12 hours on days 1, 3, and 5 and the dose was reduced to 1.5 g/m² for pts ≥ 60 yo. All cycles of HiDAC were dosed based on age, renal, and hepatic function. There were no empiric dosage adjustments based on renal function alone. Post-treatment, patients received antibiotic prophylaxis and growth-factor support. Patients returned twice weekly for blood work until neutrophil and count recovery.

Results: Forty-three patients received 88 cycles of HiDAC as an OP. The median patient age was 49 yrs (23–74) with 16% being over 60. Patient baseline characteristics of the OP group were similar to the inpatient group from our institutional review with respect to age, body surface area, gender, and race. Diagnosis, history of CNS radiation/disease, intrathecal chemotherapy, alcohol abuse, cumulative cytarabine dosage, and concurrent medications were also similar between the two groups. Only 1 patient was ineligible to receive OP therapy which was the result of both renal (estCL < 60mL/min) and hepatic (alk phos > 3X ULN) risk factors. Two patients with moderate renal insufficiency (est CL 30–60 mL/min) received full dose HiDAC without adverse event. All 43 patients successfully completed their full course of therapy. During the 88 cycles, there were no cases of clinically significant neurotoxicity (≥ grade III). There were 3 instances of grade I nystagmus. In all cases, therapy was completed without interruption. Rates of admission to the hospital post HiDAC OP consolidation for neutropenic fever (NF) was comparable to the inpatient group from our institutional review, occurring in 26% and 37% (p=0.07), respectively. All admissions post HiDAC OP was secondary to NF with the exception of one patient who was admitted for mucosal bleeding.

Conclusions: In the present analysis, we confirm the safety and feasibility of OP-based HiDAC chemotherapy for the management of AML patients in remission. If patients are dosed and monitored properly, HiDAC can be successfully transitioned to the OP setting. With the implementation of this approach, we have improved patient convenience and satisfaction, decreased pressure on inpatient resources (nearly 450 days of hospital bed use), while maintaining similar rates of hospital re-admission. With proper patient selection, dosing, and education of both providers and patients, HiDAC can be safely administered in the OP setting and has become our standard of care.