Sociodemographic Disparities in Chemotherapy and Hematopoietic Cell Transplantation Utilization Among Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia Patients

Introduction:Chemotherapy and hematopoietic cell transplantation (HCT) are cornerstones of therapy for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Identifying sociodemographic factors affecting utilization of chemotherapy and HCT may help improve outcomes for more patients with acute leukemia.

Methods: Using the California Cancer Registry, we performed a retrospective population-based study of treatment administration in patients ≥15 years of age diagnosed with ALL (n=3,221) or AML (n=10,029) between 1/2003 and 12/2012. The effect of age, sex, race/ethnicity, marital status, neighborhood socioeconomic status (nSES), and distance from nearest transplant center on the receipt of no treatment, chemotherapy alone, or chemotherapy followed by HCT was assessed. Chemotherapy and HCT were common events ensuring that odds ratios for treatment would overestimate relative risk (RR). Log-binomial and negative binomial regression models did not converge so Poisson regression with robust confidence intervals was used to estimate crude and adjusted RR with 95 percent confidence interval limits (CIs). Model fitness assumption using Pearson's chi-squared tests did not reveal over dispersion. Testing for multicollinearity showed no highly correlated covariates. Influence analysis did not identify influential observations or critical outliers. The Cochran-Armitage test for trend was used to assess changes in treatment utilization over time. Predictors were selected a priori based on published studies. Google maps API was used to compute the shortest driving distance between place of residence and nearest transplant centers. All statistical tests were 2-sided and conducted at a significance level of 0.05.

Results: Patients <60 years of age comprised 75.5% of ALL and 31.5% of AML patients. Females represented 43% of ALL and 45% of AML patients. ALL represented 47.3% of acute leukemia cases in Hispanics versus 20.5%, 19.0% and 15.6% in Asian/other, non-Hispanic blacks, and non-Hispanic whites, respectively. Among ALL patients, 11%, 75% and 14% received no treatment, chemotherapy, or chemotherapy followed by HCT, respectively. For AML patients, 36% received no treatment while 53% and 11% were treated with chemotherapy or chemotherapy followed by HCT, respectively. HCT rates were highest in 40-59 year-old (yo) ALL patients (21.3%) and 15-39 yo AML patients (31.3%). Only 3.4% of ALL patients and 3.6% of AML patients over ≥60 yo underwent HCT. Covariate-adjusted findings showed a decreasing RR of chemotherapy with increasing age for ALL (trend p <0.001) and AML (trend p <0.001). Compared to 40-59 yos, those ≥60 years of age had reduced utilization of chemotherapy and HCT [ALL, RR 0.20 (95% CI=0.14-0.29); AML, RR 0.23 (95% CI=0.20-0.26)]. Overall, older acute leukemia patients showed increasing utilization of chemotherapy and HCT over the study period. For ALL patients ≥60 yo, chemotherapy utilization was stable (p=0.38) while HCT utilization increased from 5% in 2005 to 9% in 2012 (p=0.03). Among AML patients ≥60 yo, chemotherapy utilization increased from 39% in 2003 to 58% in 2012 (p<0.001) and HCT utilization from 5% in 2003 to 9% in 2012 (p<0.001). Relative to non-Hispanic whites, lower HCT utilization was observed in Hispanic white [ALL, RR=0.80 (95% CI =0.65-0.98); AML, RR=0.86 (95% CI =0.75-0.99)] and non-Hispanic black patients [ALL, RR=0.40 (95% CI =0.18-0.89); AML, RR=0.60 (95% CI =0.44-0.83)]. Compared to married patients, never married patients had a lower RR of receiving chemotherapy [ALL, RR=0.96 (95% CI=0.92-0.99); AML, RR=0.94 (95% CI=0.90-0.98)] or HCT [ALL, RR=0.58 (95% CI=0.47-0.71); AML, RR=0.80 (95% CI=0.70-0.90)]. Lower nSES quintiles predicted lower chemotherapy and HCT utilization for ALL and AML (Trend p <0.001).For ALL and AML, the lowest SES quintile had a lower RR of chemotherapy [ALL, RR= 0.95 (95% CI 0.90-0.99); AML, RR=0.89 (95% CI 0.84-0.94)] and HCT [ALL, RR=0.63 (95% CI 0.47-0.84); AML, RR=0.52 (95% CI 0.43-0.64)] compared to the highest nSES quintile. Distance from a transplant center had no impact on the receipt of chemotherapy or HCT.

Conclusions: Older age, lower neighborhood SES, and being unmarried predicted lower utilization of both chemotherapy and HCT among ALL and AML patients. Addressing these disparities may increase utilization of known curative therapies and improve survival in underserved acute leukemia patients.