14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group.

PURPOSE: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin's lymphoma. PATIENTS AND METHODS: From July 1997 until March 2000, 94 patients with Hodgkin's lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. RESULTS: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin's lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. CONCLUSION: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin's Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.

Abnormalities of cutaneous microcirculation in atopic eczematics.

There are signs of abnormal microcirculation in atopics, yet reliable methods for its non-invasive measurement are scarce so far. Since the phenomenon of dermographism (D) elicited by blunt stroking of the skin reflects the functional response of cutaneous vessels to pressure, we studied the haemodynamics of D using laser-Doppler microfluxometry (LDF) and infrared thermography (IR-TH) in patients with atopic eczema (n = 23) and in healthy controls (n = 21) under standardized investigative conditions. Only in-patients not treated with corticoids were selected. LDF values showed a marked reduction in the intensity of hyperaemia in the patients as compared with the controls, according to the visual degree of the dermographic blanching effect (white, delayed white, indifferent; pink). A reduction of the radiating skin temperature vis-à-vis the controls was measured by IR-TH. These results yield evidence that dermographic pallor of atopic skin depends on the strength of local vasoconstriction, possibly including altered blood flow in cutaneous shunt vessels.

Non-invasive measurement of the vascular dynamics of dermographism--comparative study in atopic and non-atopic subjects.

There is no dissent about the vascular origin of dermographism (D); however, the microcirculatory events underlying this phenomenon are not yet elucidated sufficiently. In particular, the vascular mechanisms producing the white D pattern in atopics are a matter of divergent hypotheses. In order to quantify the D phenomenon reproducibly, we constructed an easily usable device called "Dermographometer" which enables us to apply constant stretching pressure to the skin. We were able to investigate several parameters of microvascular cutaneous reaction to defined skin stretching pressure by laser-Doppler-microfluxmetry and infrared-thermography. These measurements were performed on 23 patients with atopic eczema (AE) and 21 healthy controls under standardized investigative conditions. Only patients under similar therapeutic regimens (no corticosteroids) with dry or lichenified skin inflammation (lumbar area) were included in the study. The basic values of laser-Doppler-fluxmetry (LDF) showed a significant reduction in the intensity of hyperemia in the patients from those in the normal controls; this reaction depended on the visual degree of the dermographic blanching effect (white, delayed white, indifferent, pale-red). Patients with white or indifferent D had the lowest rises in blood flux; those with delayed white or pale-red D had more elevated blood fluxes, but these were still clearly below the mean levels of normal red D. Infrared-thermography showed a significant diminution of both the rise and plateau phase of the radiating temperature in comparison to the controls. Our results support the hypothesis that white D (including different subtypes of its pallor) depends on the degree of local vasoconstriction, possibly in combination with altered blood flow in cutaneous shunt vessels.

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.