A Single Institution Analysis of Incidence of Recurrent Chromosomal Abnormalities in Adult ALL Patients According to Race, Gender, and Age

Despite advances in treatment, adult patients with ALL (acute lymphocytic leukemia) have lower cure rates and decreased survival compared to children. These differences in outcome are partially attributed to unfavorable cytogenetic mutations that are more prevalent in adults than children, including the Philadelphia chromosome (Ph+). Some studies of pediatric ALL patients indicate the presence of racial disparities in outcomes and response to therapy which may be associated with genotypic variance across racial groups. There is limited published data of prevalence of cytogenetic abnormalities in adult ALL patients according to race, gender, and age. In our study, we evaluated the association of the incidence of recurrent cytogenetic abnormalities with race, gender, and age in adult patients with ALL.

275 patients (aged 17–95yo) diagnosed with ALL at Wake Forest University within the past 25 yrs were identified by reviewing the Cancer Registry database. Cytogenetics from patients' initial diagnostic bone marrow were reviewed and grouped by prognostic significance. Genotypes were sorted into normal (no abnormalities), Philadelphia chromosome t(9;22), hyperdiploid (>50), hypodiploid (30-39), t(4;11), t(8;14), and other (including tetrasomy 13 and multiple rearrangements). Genotypes were further grouped into normal, favorable (hyperdiploidy), or unfavorable (Ph+, hypodiploidy, t(4;11), t(8;14), other). Associations of prevalence of cytogenetic groups with race, age and gender were analyzed with Chi- squared tests.

This study included 275 patients, sorted by gender (114 women, 161 men); by race (233 white, 31 black, 11 other non-black minorities); and by age (33 patients <30 yo, 87 patients 30–55 yo, and 155 patients >55 yo). There was a statistically significant difference in age distribution across genders, with a higher percentage of women in older age groups than men, p=0.039. Overall, cytogenetics were distributed as follows: 41.5% (114) normal; 18.5% (51) Ph+, 6.2% (17) hyperdiploid, 2.2%(6) with t(4;11), 1.8% (5) Ph+ and hyperdiploid, 1.5%(4) hypodiploid, and 1.1%(3) with t(8;14). These genotypes are more broadly categorized as 41.5 % normal, 6.2% favorable, and 52.4% unfavorable.

Between racial groups, there was no statistically significant difference in the distribution of Ph+ and hyperdiploidy or normal, favorable, or unfavorable cytogenetic groups. However, between genders, there was a statistically significant difference in the distribution of incidence of normal, favorable, and unfavorable cytogenetic groups, p=0.015. There was a greater incidence of favorable hyperdiploidy in men, 9.3% (15), compared to women, 1.8% (2), p=0.010. There was a greater incidence of unfavorable Ph+ in women, 26.3% (30), compared to men, 16.1% (26), p=0.039. Furthermore, between age groups, there was a statistically significant difference in the distribution of incidence of normal, favorable, and unfavorable cytogenetic groups, p=0.020. There was a higher incidence of Ph+ in patients age 30–55yo, p=0.010, with 12.1% (4) patients age<30 yo, 31% (27) patients age 30–55yo, and 16.1% (25) patients age > 55 yo. Also, there was a trend toward higher incidence of favorable hyperdiploid mutation in older patients, p=0.082, with 9.0% (14) patients age>55 yo.

Our data indicate statistically significant differences in incidence of cytogenetic abnormalities across gender and age groups, but not across racial groups. By prognostic significance, there were increased incidences of unfavorable Ph+ mutations in both women and older patients, and favorable hyperdiploidy in men. Women were more prevalent in older age cohorts, which may partially account for an increased incidence of Ph+ in older patients in this study. Between racial groups, there was no difference in incidences of normal, favorable hyperdiploidy, unfavorable Ph+ and other unfavorable cytogenetics. While our ability to detect differences is limited by the relatively few minorities within the dataset, our findings suggest that differences in outcome between races may not be driven by cytogenetic risk. Disparities in response to therapy and outcomes in adult ALL patients may be related to age and gender, in addition to other factors. Further validation with a larger, more diverse patient population may enable us to identify risk factors of prognostic significance and target therapy.

No relevant conflicts of interest to declare.