Transition of Intensive Chemotherapy for Acute Lymphoblastic Leukemia (ALL) to the Outpatient Setting: Analysis of Safety and Cost Savings
Authors: Kubal Timothy E. , Salamanca Christopher Rodriguez , Chavez Julio C , Shah Bijal D. , Komrokji Rami S. , Ho Viet Q. , Lancet Jeffrey E 
Published: October 2019

Abstract
Background: ALL is an aggressive hematologic malignancy traditionally treated with intensive inpatient-based chemotherapy, which can require prolonged hospitalizations both for the delivery of chemotherapy and subsequent side effects including infectious complications and cytopenias. In addition, chemotherapeutic CNS prophylaxis further intensifies the regimen and the logistical challenges associated with its delivery. While inpatient delivery of chemotherapy may mitigate some of the logistical and clinical challenges, as healthcare moves towards a value oriented approach, delivery of these services in an outpatient setting that could lower the cost of care may offer significant value to the patient and institution. We report on our institutional experience of shifting the commonly used Hyper-CVAD regimen ("Arm-A") into the outpatient setting.
Methods: Hyper-CVAD consists of an "A" Arm (Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone) and a "B" Arm (Methotrexate and Cytarabine). From 5/2014-6/2015, 24 patients received Hyper-CVAD Arm-A for ALL (18 patients) or high-grade lymphoma (6 patients) in the outpatient setting. Median age was 35.7 years (range of 20-67). A total of 50 cycles of HyperCVAD Arm-A were delivered to these 24 patients: an average of 2.1 cycles per patient. The majority of patients (n=21, 88%) received the first cycle of Hyper-CVAD as inpatient. Doses and schedule of chemotherapy as follows: Cyclophosphamide 300mg/m2/dose IV over 3 hours Q12 hours x 6 on days 1-3, Vincristine 2mg IV over 10 minutes x 1 on day 4, Doxorubicin 50mg/m2 IV over 15 minutes x1 on day 4, Dexamethasone 40mg PO daily on days 1-4 and 11-14. Modifications to the regimen to facilitate outpatient administration included the delivery of cyclophosphamide over 1 hour in the morning and evening doses (reduced from three hours) with evening cyclophosphamide delivered approximately 10 hours after morning dosing. Additionally, on days 1-3, each patient received mesna via a 24 hour ambulatory pump with pump change each day during morning chemotherapy sessions. Daily urinalyses were performed. Cost of regimen delivery was estimated through work with our financial analysis group and includes expected gross charges for chemotherapy and any hospitalization associated with the delivery of chemotherapy.
Results: None of the 24 patients died during the period of outpatient administration of Hyper-CVAD. In addition, there were no occurrences of hemorrhagic cystitis. While there were predictable complications, including infections that required hospitalization, these occurred after completion of chemotherapy, during the period of neutropenia. Only 1 patient (4%) required admission for chemotherapy mid-cycle due to concerns for compliance with outpatient therapy. Overall, we estimated that 200 hospital days were saved over the examined time period. Administration of a cycle of Hyper-CVAD, Arm-A in the outpatient setting was accompanied by an approximate 13% reduction in gross charges ($2541). Thus, over the course of this 13 month time period, administration of outpatient Arm-A of HyperCVAD was accompanied by an estimated reduction in the cost of care of $127,050 amongst 24 patients.
Conclusion: Outpatient administration of Arm A of Hyper-CVAD was feasible, safe and well tolerated, while significantly reducing the overall cost of care associated with its delivery. Future efforts and larger studies to transition traditional inpatient chemotherapy regimens to the outpatient setting appear warranted.

Disclosures
Shah: Acetylon: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Speakers Bureau; Spectrum: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PLexus Communications: Honoraria; Bayer: Honoraria; Rosetta Genomics: Research Funding; Seattle Genetics: Research Funding. Komrokji:Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau; Incyte: Consultancy; Celgene: Consultancy, Research Funding. Lancet:Amgen: Consultancy; Kalo-Bios: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding; Boehringer-Ingelheim: Consultancy; Pfizer: Research Funding.