Healthcare Costs Associated with Adult Philadelphia Chromosome-Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) in the US
Authors: Princic Nicole , Song Xue , Lin Vincent , Cong Ze 
Published: October 2019

Abstract
Background: Ph- ALL in adults is a very rare disease with poor prognosis. Literature on the economic burden of Ph- ALL in adults is sparse. This study quantifies the economic burden by estimating the total healthcare costs of Ph- ALL in adults from initial diagnosis until relapse and from relapse until death from US payer's perspective.
Methods: This is a retrospective, observational study using the MarketScan® Commercial Claims and Encounters (Commercial) database, which contains information on approximately 40 million employees and their dependents. Patients were included if they are newly diagnosed with ALL, defined by absence of ALL ICD-9-CM diagnosis (204.0x) 90 days prior the first ALL diagnosis, and have at least one inpatient claim with ALL diagnosis (204.0x) as the primary discharge diagnosis during the study period (4/1/2009-12/31/2014). Patients with less than 6 months of continuous enrollment prior to the index date were excluded. Patient with Ph+ disease (defined by the use of any prescriptions for tyrosine kinase inhibitors) were also excluded. Relapse ALL cases were defined by patients with records of relapse code (204.02). The admission date of the hospitalization with ALL primary discharge diagnosis was the index date. Patients were followed from the index date until death, loss of follow up, or end of the study period, whichever came first.
Direct medical and pharmacy costs (plan reimbursed amounts) were the primary outcomes in this analysis. All costs were inflated to 2014 dollars based on the Medical Care component of the Consumer Price Index. Costs were evaluated monthly and cumulatively. To account for censoring in cost data, the Kaplan Meier Survival Estimator (KMSE) method (Lin et al Biometrics 1997;53:419-434) was employed to adjust the monthly costs by the Kaplan Meier curves. The total per patient cost from ALL diagnosis to death was calculated by adding the 12-month KMSE adjusted cumulative costs from ALL diagnosis to relapse and from relapse to death.
Results: A total of 362 newly diagnosed patients with Ph- ALL met all the study criteria. The average age was 41.2 (SD 15.1). Mean duration of follow-up was 409.5 days (SD 371.6) and 19% (n=69) of patients relapsed during follow-up. Mean monthly costs were the greatest during the first month following initial ALL diagnosis ($150,969) and during the first month following the relapse diagnosis ($155,321). The KMSE adjusted cumulative costs from initial ALL diagnosis until relapse per patient were estimated to be $412,231 at 6 months, and $595,509 at 12 months. The KMSE adjusted cumulative costs per patient from relapse to death were estimated to be $414,787 at 6 months, and $501,084 at 12 months. When combined, the calculated total cost per patient from newly diagnosed to relapse and from relapse until death was $1,096,593.
Conclusions and Limitations: Ph- ALL in adults is associated with significant economic burden in the US. For an average patient, the total healthcare cost from ALL diagnosis until death is more than $1 million with almost half of the expense incurred after relapse. The primary limitation for this analysis is the small sample size for the relapse ALL patients. However, it is expected given the rarity of the disease.

Disclosures
Princic: Truven Health Analytics: Employment. Song:Truven Health Analytics: Employment; Amgen: Other: This study was funded by Amgen.. Lin:Amgen: Employment. Cong:Amgen: Employment.