Successful mobilization of peripheral blood stem cells with the DHAP regimen (dexamethasone, cytarabine, cisplatinum) plus granulocyte colony-stimulating factor in patients with relapsed Hodgkin's disease.

High-dose chemotherapy followed by autologous stem cell transplantation can improve the outcome of relapsed and refractory Hodgkin's disease (HD) patients. The objective of the trial was to determine the mobilizing potential of the DHAP salvage regimen (dexamethasone, cytarabine, cisplatin) for the collection of peripheral blood stem cells (PBSC) in patients with relapsed HD. The target yield of harvesting CD34 + cells was > or =2 x 10(6)/kg in order to support the subsequent myeloablative chemotherapy. Most of the 105 patients included were intensively pre-treated with different combination chemotherapy regimens prior to mobilization. The use of DHAP followed by granulocyte colony-stimulating factor (G-CSF; 10 microg/kg) resulted in the successful collection of adequate numbers of PBSC in 97.1% of patients (102 of 105) with a median harvest of CD34+ cells of 13 x 10(6)/kg (range 2.6 - 85.1). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 65 of 103 (63%) patients after 1 apheresis, the maximum number of aphereses for all patients was 3. It was found that the optimal time of PBSC harvest was at days 13 - 16 after initiating the mobilization regimen. These results demonstrate that the salvage chemotherapy regimen, such as DHAP combined with G-CSF, can be successfully used to mobilize PBSC in HD patients.

Can factors influencing in-patient treatment in Hodgkin's disease be identified?--Retrospective analysis of HD6 patients of the GHSG.

Patients receiving chemotherapy for Hodgkin's disease can potentially be treated in the out-patient department. In spite of this the proportion of patients receiving the chemotherapy on in-patient departments is 54% per chemotherapy cycle in average in the HD6 trial for advanced Hodgkin's disease of the German Hodgkin Study Group (GHSG). The aim of this retrospective analysis is to identify the set of parameters which influence the decision of in- or out-patient treatment for the patients in the HD6 trial. Parameters tested in the univariate analysis are the patient characteristics, the type of chemotherapy, toxicity and the type of treatment institution. The significant parameters are included in a logistic regression model. From this multivariate analysis the type of treatment institution turned out to be the most important factor in the decision of treatment setting. Restricting the analysis to university clinics, the treatment setting of the first two cycles is more influencial than patient dependent parameters.

Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group.

BACKGROUND: The optimal treatment of elderly patients with Hodgkin's lymphoma (HL) is still a matter of debate. Since many of these patients receive combined modality treatment, we evaluated the impact of different radiation field sizes, that is extended-field (EF) or involved-field (IF) technique when given after four cycles of chemotherapy. PATIENTS AND METHODS: In the multicenter HD8 study of the German Hodgkin Study Group, 1204 patients with early-stage unfavorable HL were randomized to receive four cycles of chemotherapy followed by either radiotherapy (RT) of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). A total of 1064 patients were assessable for the analysis. Of these, 89 patients (8.4%) were 60 years or older. RESULTS: Elderly patients had a poorer risk profile. Acute toxicity from RT was more pronounced in elderly patients receiving EF-RT compared with IF-RT [World Health Organization (WHO) grade 3/4: 26.5% versus 8.6%)]. Freedom from treatment failure (FFTF, 64% versus 87%) and overall survival (OS, 70% versus 94%) after 5 years was lower in elderly patients compared with younger patients. Importantly, elderly patients had poorer outcome when treated with EF-RT compared with IF-RT in terms of FFTF (58% versus 70%; P = 0.034) and OS (59% versus 81%; P = 0.008). CONCLUSION: Elderly patients with early-stage unfavorable HL generally have a poorer risk profile and outcome when compared with younger patients. Treatment with EF-RT instead of IF-RT after chemotherapy has a negative impact on survival of elderly patients and should be avoided.

International harmonization of trial parameters in malignant lymphoma.

Despite the publication of standardized response criteria for non-Hodgkin's lymphomas by Cheson et al., an examination of current trial parameters in nine international lymphoma study groups by the working group for quality management (WG-QM) of the Competence Network Malignant Lymphoma found differences or even missing definitions. This finding led V. Diehl, B. Cheson, and B. Pfistner to found an international project to harmonize trial parameters for malignant lymphoma. Committees of international experts on various aspects of clinical trials design and execution were formed with the charge of summarizing the current status of each aspect of trial conduct, developing a consensus as to the most current definitions, and publishing the report of those deliberations.

A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly).

In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.

[Quality standards and their assurance for study centers in the competence network malignant lymphoma]. / Qualitätsstandards und ihre Sicherung für Studienzentralen im Kompetenznetz Maligne Lymphome.

BACKGROUND: The aim of most of the trials of the Competence Network Malignant Lymphoma is to optimize the standard treatment of lymphoma using only registered drugs in the case of medicinal therapies (quality assurance protocols). In contrast to regulatory trials, special regulations for quality assurance protocols are not given by the legislature. However, there is agreement that also for this type of studies the declaration of Helsinki and the Guidelines of the International Conference on Harmonisation (ICH) are relevant. The ICH Guidelines must be formulated to take into account the specific situation of quality assurance protocols and to ensure at the same time efficiency and transparency of these studies. This is the aim of the quality management of the study groups in the Competence Network Malignant Lymphoma. METHOD: The quality assurance measures already established in the study groups are being expanded to a comprehensive quality management concept in agreement with the ICH Guidelines and allowing for the situation of quality assurance protocols. To this end, a working group for quality management (AG-QM) has been set up to define and establish general quality standards for all aspects of planning, executing and evaluating quality assurance protocols in study centers. RESULTS: The AG-QM has developed a system of Standard Operating Procedures (SOPs) reflecting all working procedures of the study centers. Furthermore, evaluation parameters for the quality of trial execution have been identified and the harmonisation of documentation parameters has been initiated. Term definitions are collected and their harmonisation coordinated. CONCLUSIONS: Development of quality standards is the first step of quality management. To ensure the realisation of these standards in practice, the AG-QM will establish quality assurance measures including continuous reevaluation of quality criteria and actualization of quality standards if necessary.

Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.