The Superior Prognosis of Female Patients with Hodgkin’s Lymphoma Is Related to More Treatment-Induced Leucopenia and Warrants a More Individualized Therapy.

Purpose: Several scores have described gender as an important prognostic factor in patients with Hodgkin’s lymphoma (HL), particularly in advanced-stages. However, so far there is no larger analysis to systematically evaluate possible gender-specific factors. The purpose of this analysis was to investigate sex differences with regard to pre-treatment and therapy-related variables and to evaluate their influence on the outcome of HL patients.

Patients and Methods: From 1988 to 1998 the GSHG conducted two generations of clinical trials for early, intermediate and advanced HL (HD4 - HD9). The present analysis comprises 4626 patients of all stages, aged 15 to 75 years, who were enrolled into these multicenter studies and treated according to the GHSG-study protocols.

Results: At a median observation time of 5.5 years, 2050 female and 2576 male patients were suitable for this retrospective analysis. Patients in each group had very similar profiles in terms of age, performance status, stage, histological subtype, clinical risk factors and prognostic factors. Slightly more nodular sclerosis subtypes and mediastinal masses were observed in women. In contrast, more men had a mixed cellularity subtype, older age, advanced stage of disease, and B-symptoms at diagnosis. Acute chemotherapy-related toxicity was distributed almost equally. However, there was more hematotoxicity in females. This difference was most obvious for leucopenia [WHO grade III/IV: 69.9 % versus 55.2 %]. Importantly, there was no higher risk of infections in female patients. Response rates being similar in both groups, however, a lower rate of relapse and death was observed in females.

Univariate analyses revealed significant better outcome in terms of FFTF and OS for females. In multivariate analyses, sex was not identified as an independent prognostic factor, however, lower stages of disease (p<.0001), less B-symptoms (p<.0001), younger age (p<.0001), and leucopenia grade III/IV (p<.0001) were significant variables to which better outcome in females can be related. Particularly, the high prevalence of leucopenia grade III/IV during chemotherapy has a clear impact on better FFTF in females. The smaller proportion of males expressing severe leucopenia also had better outcomes. In addition, when only those patients were included who developed leucopenia grade III/IV within the first two cycles of chemotherapy, the factor maintains its protective role.

Conclusion: In this large retrospective analysis of the GHSG database, a better outcome is observed for female patients compared to male patients with HL. The protective role of severe leucopenia supports the rationale for a more individualized therapy, that may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.