Mortality during Treatment of Patients with Advanced Hodgkin’s Lymphoma Undergoing Dose Escalated BEACOPP Chemotherapy: An Analysis of the German Hodgkin Study Group (GHSG).

Introduction: Due to substantial clinical progress over the past decades, the outcome of patients with Hodgkin’s Lymphoma (HL) has improved with a long-term disease free survival of nearly 80%. Even patients with advanced-stage HL show a five year freedom from treatment failure (FFTF) of 87% and overall survival (OS) of 91% when treated with 8 cycles of BEACOPP_escalated (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbacine, prednisone). However, BEACOPP_escalated has been associated with some acute and long-term treatment related mortality (TRM). We thus analysed the incidence, clinical features and risk factors for TRM of patients treated with BEACOPP_escalated in the HD12 multicenter trial of the GHSG performed between 1998 and 2002. The HD12 was conducted for advanced HL patients (Stage IIB with large mediastinal mass and/or extranodal involvement, stage III/IV). All patients received 8 cycles of chemotherapy either 8x BEACOPP_escalated (Arm A/B) or 4xBEACOPP_escalated + 4xBEACOPP_baseline (Arm C/D) +/− 30Gy radiation on bulk and residual tumor.

Results: In this study, 43 patients (3.1%) from a total of 1392 included died from TRM. 5 patients were excluded from this analysis because of various reasons (change of fist-line therapy due to toxicity, TRM in BEACOPP_baseline) 38 patients were eligible for this analysis. 30 patients (79%) had infectious complications, 6 (16%) cardiac events such as arrhythmia or heart failure, 1 patient died due to bleomycin-related toxicity and 1 case remained unclear. 25 patients (66%) were older than 50 years in contrast to the whole HD12 study population with only 17% of patients being older than 50. There was no statistical difference between those cases with treatment related mortality and the whole study population in terms of other clinical risk factors such as gender, B-symptoms, extranodal involvement, stage of disease, large mediastinal mass or elevated ESR. There was also no difference between the 4 study arms. Most events occurred during the first 4 courses of BEACOPP_escalated (79%) with the majority during the first cycle (n = 12; 32%). 23/26 (89%) of patients who died during cycles 2 – 8 had prior WHO grade III/IV leucopenia or infection.

Conclusion: Patient age and toxicity in previous cycles are the most obvious risk factors for TRM in patients with advanced HL undergoing BEACOPP_escalated chemotherapy. In the HD12 study, the use of G-CSF was mandatory and most patients received their treatment on an outpatient basis. Thus, possible measures to reduce toxicity with this treatment include the prophylactic use of antibiotics as well as treating those with risk factors at least for the first course as inpatients.