Purpose: A systematic analysis of gender-specific factors in Hodgkin’s lymphoma (HL) studies previously revealed a better outcome for female HL patients. Factors contributing to better prognosis among female patients not only included more favorable risk factors at diagnosis, but also more treatment-induced severe leuopenia (WHO grade III/IV). The purpose of the current analysis was to characterize and investigate the protective role of severe leucopenia for both, male and female HL patients.

Patients and Methods: 4626 HL patients including 2050 females (f) and 2576 males (m) of all prognostic risk groups who were enrolled into the multicenter studies HD4-HD9 of the GHSG were evaluated. The median follow-up after treatment was 5.5 years.

Results: Female patients had a significantly better freedom from treatment failure (FFTF) with 81% at 66 months (95% confidence interval 79% – 82%), when compared with male patients (74%; 72% – 76%; p<.0001). This was in part related to the occurrence of more acute chemotherapy-related leucopenia (WHO grade III/IV): 69.9% in female patients and 55.2% in male patients (p<.0001). Furthermore, severe leucopenia during chemotherapy was strongly associated with better FFTF for both, male and female patients. Separate multivariate analyses showed that severe leucopenia remained significant when only male patients were included (0.011).

In addition, patients who developed severe leucopenia within the first two cycles of chemotherapy also had a significantly better FFTF (p=.0002) compared with all other patients (Klimm et al, JCO in press). When considering patients with advanced HL undergoing BEACOPP in baseline or escalated dose, the presence of severe leucopenia during chemotherapy (p=.0074) was associated with a better outcome. This finding was also confirmed when only the first two cycles of treatment were analyzed (p =.0205).

Conclusion: The protective role of severe leucopenia suggests evaluating of a more individualized therapy in future trials, that may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.

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