Search

Evaluates the efficacy and toxicity of a drug regimen combined with involved-nodal-field radiotherapy in advanced Hodgkin's disease not treated by chemotherapy. Complete remission rate of 94%; Complications associated with the therapy.

Twenty-six patients with relapsed or refractory Hodgkin's disease (HD) were treated with an intensive salvage regimen combining ifosfamide (3000 mg/m2/d, days 1–4 through continuous intravenous infusion) and vinorelbine (25 mg/m2, i.v. days 1 and 5) with mesna uroprotection and G-CSF support. Courses were given at 3-week intervals. Ten patients achieved a complete and 10 patients a partial response, yielding an overall response rate of 77%. The main toxic effect was neutropenia and the combination was well tolerated. [ABSTRACT FROM AUTHOR]

Unlabelled: The majority of patients with Hodgkin's disease can be cured by combination of polychemotherapy and radiotherapy (RT) that can produce late toxic pulmonary and cardiac effects which often remain at a subclinical level. The aim of the present investigation was to compare the late pulmonary and cardiac toxicity of three chemotherapeutic regimens combined with RT and particularly doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), vincristine, epirubicin, cyclophosphamide, etoposide and prednisone (VEBEP) and ABVD with mechloretamine, vincristine, procarbazine and prednisone (MOPP)., Patients and Methods: We investigated 147 patients suffering from Hodgkin's disease after a follow-up of at least 5 years from the completion of CT-RT. Seventy-eight patients were submitted to ABVD-RT, 36 to VEBEP-RT and 33 to MOPP-ABVD-RT. Patients underwent spirometry, 2D-doppler echocardiography at rest, cardiopulmonary exercise test on cycloergometer and determination of cardiac output by a non invasive method., Results: Patients of the three different treatment groups showed tolerance to exercise, and oxygen consumption significantly lower than the predicted values but there were no statistically significant difference between the three groups. Nevertheless, patients treated with VEBEP and with MOPP-ABVD showed an ejection fraction at rest lower than those observed in the ABVD group and patients treated with VEBEP showed a cardiac output for oxygen uptake lower than those observed in the ABVD and MOPP-ABVD treatment groups., Conclusion: These data confirm that the combination of mediastinal RT with the more commonly used polychemotherapy regimens produce late toxic effects. The lower exercise capacity seems to be due to a combination of decreased cardiac performance and impairment of ventilation. The VEBEP regimens could be potentially more toxic for the heart, probably because of the higher cumulative dose of anthracyclines.

Purpose: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome., Experimental Design: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry., Results: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone., Conclusions: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.

The aim of the present investigation was to evaluate lung function and the time course of serum concentration of selected cytokines known to be involved in pulmonary fibrosis, in 39 patients with stages IIB, III and IV Hodgkin's disease submitted to intermediate-high dose chemotherapy, (epirubicin, vincristine, cyclophosphamide, etoposide, prednisone) followed by radiotherapy. Lung function tests were performed before, at the end of treatment and after a follow-up of more than 12 months from the end of the combined therapy. Tumor necrosis factor alpha, fibronectin and Interleukins 4, 6 and 8 were determined on serum samples collected at the same time intervals. In the patients, spirometric parameters apparently improved whereas diffusing capacity for CO (DLCO) decreased, TNF-alpha concentrations constantly decreased, fibronectin and IL-8 showed a tendency to increase, but Interleukins 4 and 6 did not show significant modifications. No significant correlations were observed between the changes of lung function tests and serum cytokine concentrations, probably because cytokine serum levels were not able to reflect events occurring in the alveolar phase.

Purpose: BAX, a proapoptotic member of the BCL-2 family of proteins, has been detected in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD), but its clinical significance is unknown. Therefore, we correlated BAX expression with presenting features and clinical outcome in untreated patients with HD., Design: Patients with biopsy-proven HD were eligible if they were untreated previously and if pretreatment paraffin-embedded tumor tissue was available. BAX was detected by immunohistochemistry without knowledge of clinical features or outcome. A tumor was considered as positive if any number of HRS cells expressed BAX, but other cutoffs of BAX expression were examined for analysis of clinical outcome., Results: We identified 260 patients with HD. The median age was 31 years, and 55% were male. HRS cells expressed BAX in 181 of 195 (93%) nodular sclerosis, 47 of 48 (98%) mixed cellularity, 1 case of lymphocyte depletion, all 6 unclassified classical HD, and all 10 lymphocyte predominance tumors. Using a cutoff of 50% positive HRS cells for BAX expression, the 5-year failure-free survival (FFS) for patients with high versus low BAX expression was 83 versus 93%, respectively (P = 0.19 by Log-rank) for 116 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens; it was 78 versus 79%, respectively, for 79 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P = 0.45 by Log-rank); it was 71 versus 81%, respectively, for 26 patients treated with nitrogen mustard, vincristine, prednisone, and procarbazine (P = 0.6 by Log-rank); and it was 72 versus 82% for 29 patients treated only with radiotherapy (P = 0.57 by Log-rank). The 5-year FFS was not statistically different when we used cutoffs of 20, 30, and 75% for BAX expression., Conclusion: BAX is often expressed by HRS cells in HD and does not correlate with FFS.