The prognostic impact of clinical and molecular features in hairy cell leukaemia variant and splenic marginal zone lymphoma

Hairy cell leukaemia variant (HCL-variant) and splenic marginal zone lymphoma (SMZL) are disorders with overlapping features. We investigated the prognostic impact in these disorders of clinical and molecular features including IGH VDJ rearrangements, IGHV gene usage and TP 53 mutations. Clinical and laboratory data were collected before therapy from 35 HCL-variant and 68 SMZL cases. End-points were the need for treatment and overall survival. 97% of HCL-variant and 77% of SMZL cases required treatment (P = 0.009). Survival at 5 years was significantly worse in HCL-variant [57% (95% confidence interval 3873%)] compared with SMZL [84% (7191%); Hazard Ratio 2.25 (1.204.25), P = 0.01]. In HCL-variant, adverse prognostic factors for survival were older age (P = 0.04), anaemia (P = 0.01) and TP 53 mutations (P = 0.02). In SMZL, splenomegaly, anaemia and IGHV genes with >98% homology to the germline predicted the need for treatment; older age, anaemia and IGHV unmutated genes (100% homology) predicted shorter survival. IGHV gene usage had no impact on clinical outcome in either disease. The combination of unfavourable factors allowed patients to be stratified into risk groups with significant differences in survival. Although HCL-variant and SMZL share some features, they have different outcomes, influenced by clinical and biological factors.