ALBERT

Description: Young adult Hodgkin lymphoma (YAHL) is associated clinically with altered immunity, including a systemic defect in cell-mediated responses. There is strong evidence of a genetic contribution to risk, so we hypothesized that heritable alterations in cytokine production associated with Th1 function may contribute to susceptibility. We identified twin pairs in whom at least one member had YAHL and measured interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-γ (IFN-γ) levels in PHA-stimulated peripheral blood mononuclear cell supernatant in 90 case-twins, 84 of their disease-free twins (unaffected cotwins), and 90 matched controls. Mean difference and mean percentage difference in cytokine levels between case-twins and controls, and unaffected cotwins and controls were determined using analysis of covariance. YAHL case-twins and their unaffected cotwins had IL-12 levels that were 60.6% (P = .002) and 49% (P = .04) lower than those of their matched controls, respectively. IL-2 levels were significantly higher in case-twins (P = .049), but not unaffected cotwins (P = .57), compared with controls. Differences in IFN-γ levels were not statistically significant in either comparison. An IL-12 polymorphism known to regulate expression was associated with a 2.8-fold (P = .03) increase in YAHL risk. Thus, both case-twins and their unaffected cotwins had a decreased ability to produce IL-12, which may contribute to YAHL susceptibility.

Description: Abstract 3069 Poster Board III-6 Background Acute lymphoblastic leukemia (ALL) is an aggressive malignancy whose incidence declines through adolescence and then increases steadily with age. Prognosis appears to be inversely related to age among adults. We sought to explore the impact of race/ethnicity on incidence and survival among adults with ALL in the United States (US). Methods We examined trends in incidence and survival among adults with ALL in the US using the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program which includes data from 17 SEER registries. We calculated the incidence rates for the most recent time period (2001-2005) because the classification for ALL subtypes was more complete during this time. For the survival analysis we used the data collected between 1975 and 2005. We categorized race/ethnicity into 5 mutually exclusive categories: non-Hispanic whites (NHW), Hispanic whites (HW), African Americans (AA), Asian/Pacific Islanders (API) and American Indians/Native Alaskans (AI/NA). Hispanic ethnicity was defined using SEER's Hispanic-origin variable which is based on the NAACCR Hispanic Identification Algorithm (NHIA); 11 patients dually coded as black and Hispanic were included in the AA group for our analyses. Few ALL cases were identified among AI/NA, so that group is not represented in the final analyses. We included ALL cases coded in the SEER registry using the International Classification of Disease for Oncology (ICD-0-3) as 9827-9829 and 9835-9837. We excluded cases of Burkitt's leukemia (n=228), cases that were not confirmed by microscopic or cytologic tests (n=132), cases that were reported only based on autopsy data (n=3) and cases whose race/ethnicity were unknown (n=20). The average annual incidence rates per 100,000 for 2001-2005, age-adjusted to the 2000 US standard population were calculated using SEER*Stat Version 6.4.4 statistical software. We used multivariate Cox hazard models stratified by SEER registry and age category to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for relative survival of adult ALL cases across race/ethnicity, sex and cell of origin (B- or T-cell). All models were adjusted for the diagnosis era, and use of non-CNS radiation. The model also included an interaction term for age and diagnosis era. We performed a separate stratified analysis of the impact of race/ethnicity on survival within age subgroups (20-29, 30-39, 40-59, 60-69, 70+). Results The highest incidence rate (IR) of ALL was observed for HW (IR: 1.60; 95% CI: 1.43-1.79). HW had a significantly higher IR across all age categories as compared to the other racial/ethnic groups, while AA had the lowest IR. In particular, the observed rate of B-cell ALL among HW (IR 0.77; 95% CI 0.69-0.87) was more than twice that of NHW (IR: 0.29; 95% CI: 0.27-0.32) and more than three times the rate observed among AA (IR: 0.20; 95% CI: 0.15-0.26). In contrast, we did not observe statistically significant variability in the rates of T-cell ALL across race/ethnic groups (overall IR: 0.12; 95% CI: 0.11-0.14). Survival was significantly poorer among AA (HR: 1.26; 95% CI: 1.09-1.46), HW (HR: 1.21; 95% CI: 1.09-1.46), and API (HR: 1.18; 95% CI: 1.06-1.32) compared to NHW with all subtypes of ALL. Among adults younger than 40 with B-cell ALL, survival was significantly poorer among AA (HR: 1.60; 95% CI:1.021-2.429) and HW (HR: 1.53; 95% CI:1.204-1.943) with a non-signficant trend among API (HR: 1.22; 95% 0.834-1.755) compared to NHW. Survival differences between the different racial/ethnic groups were no longer statistically significant among adults with B-cell ALL over the age of 40. For T-cell ALL, survival was significantly poorer among AA (HR: 1.61; 95% CI: 1.22-2.10), HW (HR: 1.49; 95% CI: 1.14-1.93) and API (HR: 1.57; 95% CI: 1.13-2.13), as compared to NHW. A similar survival pattern by age (adults above and below age 40 years) was observed for T-cell as described for B-cell, with AA under 40 having a particularly dismal prognosis (HR: 2.89; 95% CI 1.96-4.17) compared to NHW. Conclusions The incidence rate of B-cell ALL among adults in the US is higher among HW than other ethnic groups. Survival is significantly poorer among AA and HW than among NHW under the age of 40 with B-cell ALL. Survival is also significantly poorer among AA, HW and API than among NHW with T-cell ALL in adults under 40. Survival trends appear to converge after the age of 40 among all racial/ethnic groups. Disclosures No relevant conflicts of interest to declare.