Outpatient Intensive Induction Chemotherapy for Acute Myeloid Leukemia and Advanced Myelodysplastic Syndrome

Introduction:

To improve patients' quality of life and reduce healthcare costs many conditions formerly thought to require inpatient care are now treated in an outpatient setting. With respect to the treatment of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we believe that outpatient induction chemotherapy may confer similar benefits, but, thus far, there has been a paucity of studies exploring the safety and feasibility of this option. The feasibility of outpatient consolidation has been established (Saini L et al Am J Hematol 2012), and we have shown that early discharge after completion of induction does not increase treatment related mortality provided patients are doing well at discharge, live near the treatment center, and have support at home (Vaughn JE et al JAMA Oncol 2015). Here we extend our findings by examining whether intensive inductionchemotherapy for AML and MDS can be safely administered exclusively in an outpatient setting.

Methods:

We conducted a pilot feasibility study. Eligible patients were ≥ age 18, met inclusion criteria for inpatient induction regimens, were without active infection, and had the following: normal chest x-ray, adequate cardiac function, expected death rate of < 5-10% within 28 days of beginning intensive therapy (Walter RB et al J Clin Oncol 2011), peripheral blast count <10 X 10^9/L, and fibrinogen level >100 mg/dL. Logistical requirements included residence near the treatment center, caregiver support, trained nursing staff, infusion room capacity, and participation in follow-up. Patients received prophylactic antimicrobials such as oral levofloxacin, fluconazole and acyclovir and were admitted to the hospital for predetermined complications of therapy (e.g. temperature > 101F, significant bleeding, severe organ toxicity). Criteria for feasibility for future study were: >50% of patients completed chemotherapy without requiring admission and <5% of treated patients died within 14 days of starting induction.

Results:

Eighteen patients were consented and 15 patients were treated with a median age 52 (range 19-72) and median TRM score 1.1711 (mean 2.5718, range 0-8.001): 7 received initial induction chemotherapy and 8 received salvage induction chemotherapy. Of those not treated, 2 were limited by scheduling constraints and 1 was found to have bilateral paraspinous extramedullary disease prompting admission. All regimens contained cytarabine at 1.5-2g/m² per dose. 12 patients completed induction chemotherapy in the outpatient setting (80%; exact 95% CI 51-95%) while 3 patients required inpatient admission: 2 for neutropenic fever and 1 for grade 3 mucositis. All 3 of these patients completed chemotherapy as inpatients without complication. No patients died within 14 days of the initiation of induction chemotherapy (exact 95% CI 0-25%). The logistical issues that arose were largely related to scheduling multiple infusions, hydration, and transfusions at our outpatient infusion center. In addition to chemotherapy, 7 patients received RBC transfusions, 5 patients received platelet transfusions, and 2 patients received IV antibiotics. Significant systems changes had to be implemented to facilitate close clinical follow up and to ensure that the AML patients received education for care of central venous lines, effects of chemotherapy including risk of infection and bleeding, and medication management. Psychosocial support was also essential for the patients and families coping with AML.

Conclusions:

Our pilot study suggests it is feasible to complete outpatient induction chemotherapy in select AML and high-risk MDS patients. An inter-professional team approach including nurses, social workers, medical providers and pharmacists was key to the successful implementation of outpatient induction. We plan to formally compare resource utilization, quality of life measures, and charges for outpatient vs. inpatient induction therapy.