Males have a worse prognosis than females in chronic lymphocytic leukemia and this may be related to IgVH gene usage and mutational status.

2211 It has been suggested that women have a better prognosis than men in chronic lymphocytic leukemia (CLL) and this could be related to hormonal or cellular differences. To assess the sex differences in CLL we have carried out a population-based study in Manitoba (pop. 1.2 million) in which we have identified all patients diagnosed with CLL or small lymphocytic lymphoma (SLL) from 01/01/1998 to 12/31/2003. Patients were identified through the Manitoba Cancer Registry with ICD codes 9 and 10 for CLL or SLL and by our centralized flow cytometry facility. 636 pts were identified (incidence, 88 pts/million/annum); the median age at diagnosis was 71 yrs with a male:female ratio of 1.3:1. There was a predominance of men to women until the age of 70 yrs and a predominace of females thereafter. The median age at diagnosis was higher for women than for men (73 vs 70 yrs, P=0.04). Moreover, women had a better prognosis than men, with the 5 year relative survival being 90% compared with 70% for men. The difference in survival increased with age being most marked in patients u003e75 yrs old. To examine the cause for this difference, we evaluated cellular prognostic indicators in males and females. Poor prognostic markers include unmutated IgVH, use of certain IgVH genes, eg. VH1-69 and VH3-21, ZAP-70 positivity, CD38 positivity and del 17p13 (p53 mutation). Of u003e300 pts followed in the CancerCare Manitoba CLL clinic 101 have to date been studied (66 male, 35 female). Overall, there was a predominance of IgVH mutated cases with the mutated:unmutated ratio being 1.6:1. There was a predominance of mutated cases in female patients with the mutated: unmutated ratio being 2.2:1, compared with 1.4:1 in males. Of the twelve VH1-69 cases, 9 were male and 3 female, and of the five VH3-21 cases, all were male. In addition, there was a predominance of ZAP-70 positivity in males compared to females, but no difference was noted in CD38 status, in vitro sensitivity to chlorambucil or fludarabine (as measured by MTT assay) or in the incidence of del 17p13 (as measured by FISH). To determine whether there was a difference in plasma to explain the sex differences, male or female CLL cells were incubated in male or female plasma and spontaneous or drug-induced apoptosis measured by acridine orange staining. To date, no consistent difference has been observed between male and female plasma.u2028 Thus, the worse prognosis for males with CLL may be related to a bias in IgVH gene usage by men and an increased likelihood of being unmutated. Further patients are being studied to confirm these findings.