Impact of Venous Thromboembolism during High Intensity Chemotherapy for Acute Leukemia Patients on Duration of Hospital Stay
Authors: Waldron Madeline , Siebenaller Caitlin , Earl Marc , Jia Xuefei , Carraway Hetty E. , Advani Anjali S. , Nazha Aziz , Gerds Aaron T. , Hamilton Betty K. , Sobecks Ronald , Kalaycio Matt , Tripp Barb , Hobbs Brian P. , Sekeres Mikkael A. , Mukherjee Sudipto 
Published: October 2019

Abstract
Background: Patients (pts) with hematologic malignancies have an increased risk of venous thromboembolism (VTE) events, driven by both the underlying cancer and cancer treatment. This risk exists even in acute leukemia (AL) in the setting of profound thrombocytopenia and coagulopathies, which can delay VTE diagnosis and complicate management. We evaluated the incidence of VTE in AL pts during an admission for chemotherapy and determined its effect on the duration of hospital stay and likelihood of intensive care unit (ICU) admission.
Methods: All pts admitted to the Cleveland Clinic inpatient leukemia service with a diagnosis of acute myeloid (AML), lymphoblastic (ALL), or promyelocytic leukemia (APL) between January 1, 2013 and March 31, 2018 and treated with high-intensity chemotherapy were included. High intensity regimens for AML and APL included infusional cytarabine and an anthracycline with the addition of ATRA for latter and for ALL included Hyper-CVAD and CALBG regimens. Pts were excluded if they were admitted directly to the ICU or were transferred after initiating chemotherapy from another institution. Cases with VTE were defined using specific ICD-9-CM codes [451.1x, 451.2; 451.81, 453.1, 453.2, 453.8, 453.9, 415.1x; and, in addition, 997.2 or 997.3 when coupled with a secondary diagnosis of VTE]. All VTE cases identified through this strategy via an electronic medical record query were additionally validated on subsequent chart review. Pts with a diagnosis of VTE were matched 1:3 based on age, sex, race, and leukemia subtype to pts who did not experience VTE during the incident admission. Pts were also assessed for administration of prothrombotic agents, including: PEG-asparaginase, oral contraceptives, and tyrosine kinase inhibitors. The length of stay for the incident hospitalization and incidence of ICU admission were compared between pts who did and who did not experience VTE.
Results: Of the 400 AL pts admitted to the inpatient leukemia service during the study period to receive high-intensity chemotherapy, 10 (2.5%) had a documented VTE during the admission. Baseline characteristics of the 1:3 matched cohorts (AL with and without VTE) are shown in Table 3. The median age of the AL pts who developed VTE was 54.5 years (range, 20-78 yrs), 60% were females, median platelet count at the time of VTE diagnosis was 117,900/mL [(range, 29-476,000/mL); 4 pts had platelet (plt) counts below 50,000/mL, 8 pts had plt below 100,000/mL; 2 pts had normal plt counts], and four pts had bloodstream infections within 7 days of VTE occurrence. By disease breakdown, four had AML, 3 had APL and 3 had ALL. By treatment course, 9 pts were receiving initial chemotherapy 1 pt was receiving salvage therapy. By VTE site, 8 patients had line associated VTE and 2 patients had pulmonary embolism. Five VTE pts were treated with either unfractionated or low molecular weight heparin, 2 underwent IVC filter placement and 3 were untreated.
Pts in the VTE group experienced a longer duration of hospitalization compared to those who did not have a VTE event (29.81 vs 23.13 days, respectively, P=.027), and were more likely to be admitted to the ICU compared to those who did not experience VTE (66.7% vs 14.8%, respectively, P=.010). VTE risk was not associated with use of prothrombotic agents (p=.430).
Summary and Conclusion: While the incidence of VTE in our patient population was lower than what has been previously reported, it was associated with a prolonged hospitalization and increased risk of ICU admission. The incidence of VTE was not associated with use of thrombotic agents and VTE events occurred in patients with normal plt counts and even in the setting of moderate or severe thrombocytopenia. While it is unclear if early intervention after the diagnosis of VTE affects clinical outcome, the association with increased length of stay and ICU admission can increase healthcare-associated costs in the current environment with increasing focus on value. Further studies are warranted to characterize the risk factors for VTE in AL population.

Disclosures
Carraway: Novartis: Speakers Bureau; FibroGen: Consultancy; Jazz: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; Balaxa: 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, Research Funding, Speakers Bureau. Advani:Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy; Pfizer: Honoraria, Research Funding. Nazha:MEI: Consultancy. Gerds:Incyte: Consultancy; CTI Biopharma: Consultancy; Apexx Oncology: Consultancy; Celgene: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.