Abstract
Introduction: Outcomes for adults with acute lymphoblastic leukemia (ALL) have improved with the development of multiple regimens, including pediatric protocols. While intensive chemotherapy may achieve high remission rates, 5-yr overall survival ranges from 5% to 55%, and is influenced by age, cytogenetics, and other factors. The primary objective of the study is to assess the survival of a unique cohort of adults with ALL treated at a safety-net public hospital. Secondary objectives are to describe demographic and clinical characteristics of this population, to assess remission rates based on the treatment regimens, and to determine the referral rate to centers for hematopoietic cell transplant (HCT).
Methods: We retrospectively analyzed adult (> 18 years) patients diagnosed with ALL who presented to Harbor-UCLA between 2000 and 2017. Patients with Burkitt lymphoma, chronic myelogenous leukemia in lymphoid blast phase, and biphenotypic leukemia were excluded. Baseline characteristics, including age, sex, race, ALL subtype, number of hospitalizations, and type of induction regimens were collected. Incidences of positive bacterial blood and urine cultures were recorded. Rates of complete remission (CR) and relapse were calculated. The number of referrals for HCT and number of patients who received HCT were noted. Kaplan-Meier survival analysis was performed for overall survival (OS) from the time of diagnosis. Univariate and multivariate subgroup survival analyses were performed based on different age groups, induction regimens, and consolidation treatment with HCT.
Results: A total of 83 patients with ALL presented to Harbor-UCLA from 2000 to 2017 and were included in this analysis. Median age at time of diagnosis was 35 years (range: 18-63); the majority of patients were male (58%) and Hispanic (71%). Of patients whose Ph status was assessed (n=48), 15 (31%) were Ph+; 33 (69%) were Ph-. Induction regimens included pediatric protocols (n=14), HyperCVAD (n=31), Linker's regimen (n=34), and others (n=2). Two (2%) patients did not receive induction chemotherapy. The median number of hospitalizations per patient was 6 (range 1-29). Of the 81 patients who received induction chemotherapy, 63 (78%) achieved CR with induction. Median time to CR was 30 days (range 0-140 days). When stratified by induction regimens, remission rates were 92% for pediatric protocols, 68% for HyperCVAD, and 79% for Linker regimens. 36 patients (44%) had relapsed or refractory disease. 32 (39%) had positive blood cultures; 23 (28%) had positive urine cultures. 25/83 patients were referred for HCT. Out of those referred, 11 (44%) underwent HCT.
We divided the study into 3 time periods: 2000-2005, 2006-2011 and 2012-2017. Over the 3 periods there was significant (p=0.04) increase 12% (n=2), 26% (n=9) and 45% (n=9) in HCT referral rates. At the time of study conclusion there were 44 deaths with a median OS of 21.9 months (95% CI, 14.4-43.4 months) and median leukemia-free survival of 23.3 months (n=59, 95% CI, 12.6-NR). 2 and 5-year survival were 46.7% (95% CI, 35.8%-60.9%) and 27.2% (95% CI, 16.8%-43.8%), respectively.
We compared outcomes in different cohorts based on age, induction chemotherapy, and HCT vs no HCT. By log-rank test, median OS was significantly improved for the age group 18-40 compared with age group ≥ 40 years (34.8 months (95% CI, 24.3 months-NR) vs 9.5 months (95% CI, 4.7-21.9)), respectively (p=0.0035). OS was not correlated with the induction regimen: pediatric protocols (43.4 months), HyperCVAD (17.4 months), Linker's (21.9 months), and others (8.2 months), with p=0.69. There was a trend for improvement in OS with a pediatric protocol, albeit with a wide confidence interval given the small numbers. The 5-year OS in the HCT group compared to non-HCT group was 55.6% (n=11) vs 25.8% (n=64), p=0.17 respectively. On multivariate analysis, only younger age was significantly associated with better OS (HR=0.43 [95% CI, 0.21-0.88], p=0.0214).
Conclusion: The 5-year OS of ALL patients treated at public safety-net hospital providing care to a medically underserved; predominantly Hispanic population was comparable to prior national estimates of OS. Age was the only predictor of OS in the multivariate model. HCT referral rates to tertiary centers in the past 5 years increased, with a trend towards improved survival with HCT. Improved collaboration with tertiary centers may improve outcomes.
No relevant conflicts of interest to declare.
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