Hematopoietic Cell Transplantation in First Remission Amongst Adolescent and Young Adult Acute Lymphoblastic Leukemia: A Population-Level Analysis across the United States
Authors: Muffly Lori S , Li Qian , Alvarez Elysia , Kahn Justine M. , Winestone Lena E. , Cress Rosemary , Penn Dolly , Keegan Theresa H.M. 
Published: October 2019

Abstract
Background:
The optimal role of allogeneic hematopoietic cell transplantation (HCT) for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) is an area of clinical debate. In this population-based evaluation of AYA ALL patients across the United States (US), we sought to describe recent patterns of care and outcomes regarding HCT in first complete remission (CR1) amongst AYAs with ALL.
Methods:
Data were abstracted from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Patterns of Care (POC) study focused on AYA cancers. AYAs (15-39 years) with ALL newly diagnosed between January 1, 2012 through December 31, 2013 and registered in the SEER program were included. Allogeneic HCT in CR1 was defined as occurrence of HCT without relapse/progression prior to the HCT date; HCT was considered a time-dependent variable in survival models. Multivariable logistic regression was used to evaluate associations with HCT in CR1; cox proportional hazards regression was used to evaluate associations with survival.
Results:
Three-hundred and ninety-nine AYAs (15-39 years) with newly diagnosed ALL between 2012-2013 were included; median follow-up for survival was 19 months (range, 0-35 months). The median age was 24 years; 85% had B-cell ALL, 27% had high risk ALL cytogenetics. One-third of AYA ALL patients received care from pediatric oncologists while two-thirds were treated by adult hematologist/oncologists; a majority (86%) received care at a teaching hospital. Fifty-eight percent received an asparaginase-containing ALL front-line regimen, 32% received hyperCVAD; 5.9% and 4.5% received another/unknown regimens, respectively. One-hundred and two (29%) AYAs underwent allogeneic HCT in CR1. Excluding patients with relapse/progression or death within three months of diagnosis (n=32), older age, high-risk ALL cytogenetics, treatment by an adult hematologist/oncologist, and front-line therapy with hyperCVAD were variables significantly associated (all P< 0.05) with increased odds of HCT in CR1 in univariate analysis, while Hispanic ethnicity and public or no/other insurance were associated with significantly lower odds of HCT in CR1. In multivariate adjusted analysis, only high-risk cytogenetics (odds ratio (OR) 4.84, 95% confidence interval (CI) 2.99-7.83) and receipt of hyperCVAD (OR 1.84, 95% CI 1.07-3.16) retained significant associations with HCT in CR1. The two-year cumulative incidence of relapse, relapse-free survival (RFS), and overall survival (OS) of the entire cohort were 28.3% (95% CI 23.4%-33.4%), 69.3% (95% CI, 63.6%-74.3%), and 84.1% (95% CI 79.7%-87.5%), respectively. Two-year cumulative incidence of relapse was significantly lower in patients receiving HCT in CR1 as opposed to those not receiving HCT in CR1 (15.1%, 95% CI 8.1%-24.1% vs 32.8%, 95% CI 26.9%-38.9%). This translated into a significant improvement in 2-year RFS (83.6%, 95% CI 72.6%-90.5% vs 64.3%, 95% CI 57.5%-70.3%), but no statistically significant differences in 2-year OS (88.9%, 95% CI 80.8%-93.7% vs 82.5%, 95% CI 77.2%-86.7%). Among all patients, receipt of care at a non-teaching hospital (hazard ratio (HR) 2.14, 95% CI 1.22-3.75) and use of another/unknown regimen (HR 9.08, 95% CI, 4.83-17.06) were significantly associated with inferior OS.
Conclusions:
In the US, allogeneic HCT in CR1 is most commonly administered to AYA ALL with high risk cytogenetics and as consolidation therapy for those who receive front-line hyperCVAD, as opposed to asparaginase-containing ALL regimens. Consistent with prior studies, AYA ALL patients treated at non-teaching hospitals have inferior survival. Although the landscape of ALL therapy is changing, these data provide an important snapshot of the modern state of HCT in CR1 for AYA ALL.

Disclosures
Muffly: Shire Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding.