Outpatient Administration Of Hyper-CVAD Chemotherapy For Acute Lymphoblastic Leukaemia / Lymphoma Is Safe and Associated With Similar Toxicity Compared To Inpatient Delivery
Authors: Abro Emad Uddin , Morris Kirk , Hodges Georgina , Butler Jason P , Curley Cameron , Pillai Elango Subramonia , Kennedy Glen A 
Published: October 2019

Abstract

Background / Aims
Increasing bed pressure in health care systems is driving delivery of chemotherapy for acute leukaemia into ambulatory care settings. In our institution patients with acute lymphoblastic leukaemia/ lymphoma (ALL) are admitted to hospital for initial induction but based on social circumstance and medical co-morbidities, subsequently receive consolidation cycles on an outpatient basis whenever possible. We aimed to examine the safety of outpatient delivery of Hyper-CVAD based chemotherapy in adult ALL patients treated at our institution.

Methods
All patients >14yrs diagnosed with B- and T- ALL between 1999 and 2011 and treated with Hyper-CVAD based induction were identified from an institutional database. During this period Hyper-CVAD was the standard chemotherapy used to treat ALL at our institution. Chemotherapy outcomes including ≥ grade 3 hepatic, renal, neurological and infectious toxicity as well as hospital length of stay for chemotherapy cycles delivered as inpatient vs. outpatient were then retrospectively determined by review of individual medical records. As the initial cycle of Hyper-CVAD (cycle 1A) was delivered on an inpatient basis in all patients, analysis of inpatient vs. outpatient chemotherapy toxicity was restricted from the 2nd Hyper-CVAD cycle and beyond. Toxicity was graded according to standard CTCAE v4.0.

Results
In total 44 patients had been treated with > 1 cycle of Hyper-CVAD for newly diagnosed ALL during the time period under review. Median age was 36 (range 14-73 yrs); 28 (64%) were male. In total 270 individual cycles of Hyper-CVAD were administered in these 44 patients, with a median of 6 cycles per patient (range 2-8). Excluding cycle 1, a total of 98 A cycles and 128 B cycles were administered, with 78 cycles (35%) delivered on an inpatient basis and 148 (65%) on an outpatient basis. A significantly greater proportion of B cycles were delivered in an inpatient setting compared to A cycles (43% vs 23%; p=0.003). Overall incidence of ≥ grade 3 toxicity was similar for inpatient vs. outpatient delivery for both A (21% vs. 21%; p=1.0) and B cycles (78% vs. 75%; p=0.8). For hepatic toxicity incidence was similar for inpatient vs. outpatient treatment for A cycles (5% vs. 5%; p=1.0), but of borderline difference for B cycles (31% vs. 15%; p=0.051), likely reflecting appropriate selection of patients with co-morbidity for inpatient treatment. Overall incidence of ≥ grade 3 renal and neurological toxicity was low (<3%) and similar in all chemotherapy subgroups. Episodes of febrile neutropenia were also similar regardless of inpatient or outpatient treatment (58% vs. 68%; p = 0.27). Despite need for admission of patients for management of infection / toxicity, commencement of chemotherapy in the outpatient setting was associated with a significantly lower inpatient length of stay per cycle compared to inpatient delivery (mean 5.5 vs.15.6 days respectively; p < 0.0001).

Conclusion
Our experience of delivery of Hyper-CVAD chemotherapy in an outpatient setting in adult ALL suggests that ambulatory-based chemotherapy is both safe and not associated with increased toxicity compared to inpatient delivery. The associated reduction in requirement for inpatient hospitalisation is likely to result in meaningful reductions in cost and resource utilisation.

Disclosures:
No relevant conflicts of interest to declare.