Hodgkin's Disease Patients Research Articles

Autologous hematopoietic cell transplantation in Hodgkin's disease

The use of HDT and AHCT in Hodgkin's disease patients with early relapsed and refractory disease is supported by historical comparisons. In regard to the late relapsed patient or the newly diagnosed high-risk patient, the role AHCT plays would ideally be answered by well-controlled phase 3 trials. A surrogate approach would be the comparison of AHCT data with well-matched historical controls. It is important, however, to be mindful of the changes that have occur red in the therapy of the newly diagnosed and relapsed HD patient (ABVD replacing MOPP regimens) and the impact these changes may or may not have on nonrelapse mortality in the autografted and nonautografted setting. In addition, the incorporation of consistent prognostic factors in any trial design may identify groups of relapsed or refractory and high-risk HD patients who may or may not gain benefit from HDT. The most effective and efficient route to answering these treatment questions is enrollment of patients in well-controlled and well-designed clinical trials. Biol Blood Marrow Transplant 2000;6(3A):289-300.

Management of relapsed Hodgkin's disease patients with high-dose chemotherapy and marrow stem-cell transplantation

Management of relapsed Hodgkin's disease patients with high-dose chemotherapy and marrow stem-cell transplantation

Cardiac transplantation in survivors of lymphoma: a multi-institutional survey.

Cardiac transplantation has been successfully performed in patients with a history of presumably cured Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Though the risk of recurrence is a major concern, the long-term influence of prior cancer and cancer therapy on posttransplant outcome has not been previously investigated. Questionnaires were sent to 130 cardiac transplant centers in the United States registered with the United Network for Organ Sharing. Data collected included patient demographics; type, stage, and timing of HD/NHL; treatment for HD/NHL; posttransplant immunosuppressive regimen, rejection history, and outcomes; and Epstein-Barr virus status. Thirty-four cardiac transplant recipients with a previous history of HD (n=16) or NHL (n=18) were identified. HD patients averaged 41+/-15 years of age, with a mean disease-free interval of 15+/-9 years at the time of transplantation. NHL patients averaged 42+/-17 years of age with a mean disease-free interval of 10+/-9 years at the time of transplantation. The mean follow-up for the entire group was 50 months (range, 2 days to 136 months), and mean follow-up for the survivors was 67 months (range, 23-136 months). The 1-, 3-, 5-, 7-, and 10-year actuarial survival estimates for the entire group are 77%, 64%, 64%, 64%, and 50%, respectively. Actuarial survival was lower in HD patients (P=0.04) and in patients who had previously undergone splenectomy (P=0.008). Cox regression analysis identified only prior splenectomy (P=0.02) as an independent risk factor for mortality after cardiac transplantation with an adjusted relative risk of 6.2 (1.7-21.9, 95% confidence intervals). Although the numbers are small, these data strongly suggest that there is an increased mortality risk for cardiac transplant recipients with prior HD who have undergone splenectomy.

Restaging with gallium scan identifies chemosensitive patients and predicts survival of poor-prognosis mediastinal Hodgkin's disease patients.

Following treatment of mediastinal Hodgkin's disease (HD), residual masses are frequent and gallium scanning has proven to be of value in the evaluation of their specificity (fibrosis or active disease). This study assessed, for relapse and survival, the predictive value of restaging gallium scan of patients with a residual mass on computed tomography scan after induction chemotherapy. Between 1/89 and 12/97, in 53 newly diagnosed HD patients with a residual mediastinal mass, a gallium scan was performed after chemotherapy (3 or 4 courses) and always before consolidative radiotherapy. Characteristics at diagnosis were: nodular sclerosis histology, 89%; bulky mediastinal disease, 79%; B-symptoms, 51%. gallium scan was positive in 16 patients (30%) and negative in 37 (70%). At median follow-up period of 36 months, freedom-from-progression rate was 86% versus 19% (P<0.0001) for patients with negative vs positive gallium scans, respectively. The 5-year overall survival (OS) rate was 68% and differed significantly (P<0.0001) between negative (91%) and positive (25%) gallium scanning groups. The specificity of gallium scanning was 91% and the sensitivity 72% with a positive predictive value of 81% and a negative predictive value of 86%. Evaluation with gallium scan after induction chemotherapy identifies chemosensitive patients among those with poor-prognosis mediastinal HD. Although relapse may occur in patients with negative gallium scan, a postive gallium scan is highly predictive of failure and poor outcome, and treatment should thus be modified.

Hybrid chemotherapy consisting of cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) as first-line treatment for patients with advanced hodgkin disease

Combination chemotherapy, including hybrid regimens, is the standard treatment for patients with advanced Hodgkin disease (HD). Although a prolonged complete response (CR) is achieved in up to 70-80% of patients, long term complications, such as secondary leukemia, are of concern. Cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) is a hybrid chemotherapy in which cyclophosphamide is substituted for mechlorethamine, an agent that has been implicated as the cause of secondary malignancies. Seventy-three patients (37 males and 36 females; median age, 35 years) diagnosed with Stage III or IV HD or Stage II with bulky disease, B-symptoms, elevated erythrocyte sedimentation rate, or hilar adenopathy were treated with 8 courses of C-MOPP/ABV at a single institution during a 6-year period. Radiotherapy (RT) was administered when bulky disease or residual masses were present. Endpoints of the study were response to therapy, failure free survival (FFS), overall survival (OS), and toxicity. Sixty-five patients (90%) received the 8 planned courses, with 49 of them (70%) receiving the full prescribed doses. After chemotherapy, 57 patients (78%) reached CR. Seven additional patients who achieved partial response (PR) reached CR after complementary radiotherapy, with an overall CR rate of 88%. The median follow-up was 31 months. Twelve patients relapsed; the 4-year FFS was 66% (95% CI, 54-78%). Two patients died during treatment because of sepsis and four due to disease progression. The 4-year OS was 92% (95% CI, 86-98%). Age > 60 years and bone marrow involvement were related to severe infectious complications. No late toxicity was reported. C-MOPP/ABV induces CR with acceptable toxicity in a high proportion of advanced HD patients.

Is the international prognostic score for advanced stage Hodgkin’s disease applicable to early stage patients?

BackgroundThe seven-factor International Prognostic Score (IPS) has been developed and verified for patients with advanced stage Hodgkin’s disease (HD). This report aims to assess the predictive power of the IPS for early stage HD patients. Patients and methodsData on patient characteristics, therapy and follow-up were available for 1424 adult patients in clinical stages I-IIIA treated for primary HD in two German Hodgkin’s Lymphoma Study Group (GHSG) trials (1988–1994). Patients with risk factors or in stage IIIA received chemo-radiotherapy (CMT; trial HD5); others received extended field radiotherapy (RT) alone (HD4). The IPS could be calculated for 712 HD5 and 249 HD4 patients (70%). The prognostic value of the IPS and its component factors was assessed using Cox proportional hazards regression. A search was made for additional factors which could add predictive power to the IPS. ResultsThe IPS identified 40% of the unfavourable early stage patients with an 8% lower disease-free survival at six years (hazard ratio 1.66, P = 0.0018). The factor ’low albumin’ was the only score component giving a significant individual contribution. Allowing for the IPS, extranodal involvement, particularly in stages IIB-IIIA, was associated with worse prognosis, but no further significantly prognostic factors were revealed. The IPS identified a similar hazard ratio in HD4, although here the effect was not significant. ConclusionsThe IPS for advanced HD has modest predictive ability in unfavourable early stage patients. Modification of the IPS for use with early stages may improve its prognostic power.

Treatment of nonlaparotomized (clinical) stage I and II Hodgkin’s disease patients by extended field and splenic irradiation

Purpose: At the New York Presbyterian Hospital–Cornell Medical Center, patients with unequivocal clinical stage I and IIA Hodgkin’s disease (HD) have been treated with mantle, splenic, and extended field radiation therapy (EFRT) (without surgical staging). A 24-year retrospective review was conducted to determine the effectiveness of our patient selection on the outcome of patients treated with this modality. Methods and Materials: During the period 1971 to 1994, 94 patients with clinically staged HD, with favorable prognostic factors, were retrospectively reviewed. Patients with pathological or equivocal staging, “B” symptoms, bulk disease, history of previous chemotherapy, and/or Stage III or IV disease were excluded from our analysis. There were 27 Stage IA and 67 Stage IIA patients. All patients were treated to 3600 cGy with a 400 cGy boost to the involved field. The median follow-up was 52 months, mean of 62.1 months. Results: Ten of 94 patients (10.5%) relapsed. Seven of the relapses were in the pelvis, one submandibularily, one in the tonsil, and one in the axilla. Nine of the relapses had nodular sclerosis histology, one had lymphocyte predominance, and none had mixed cellularity. The median time to relapse was 38 months; mean time 42.3 months. All patients are alive, well and free of disease, including nine who received subsequent chemotherapy and one who underwent autotransplantation. Conclusions: Careful clinical staging of early, asymptomatic HD patients treated with mantle, splenic, and EFRT may obviate the need for exploratory laparotomy.

Conventional salvage chemotherapy vs. high-dose therapy with autografting for recurrent or refractory Hodgkin's disease patients.

Despite progress that has been made in curing Hodgkin's disease (HD), patients whose first remission is brief and those resistant to first-line chemotherapy still have a poor outcome. We retrospectively reviewed data from 29 patients with HD in first relapse or refractory to first-line chemotherapy. Following failure, all patients received three cycles of ifosfomide, epirubicin, and etoposide (IEV); moreover, 11 patients received a conditioning regimen followed by autografting. Of the 18 patients treated with IEV, eight (44%) are alive; nine died of disease progression, and one died of hematologic toxicity. The 24-month overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) are 18%, 44%, and 22%, respectively. Of the 11 patients treated with IEV and autografting, ten are alive (90%) and one patient died of progressive disease. The 29-month OS, RFS, and EFS are 91%, 71%, and 56%, respectively. Our results confirm data showing that patients with relapsed or resistant HD achieve a significantly better OS and EFS if treated with high-dose therapy and autografting.

Long-term survival in Hodgkin's disease patients: a comparison of relative survival in patients in trials and those recorded in population-based cancer registries

The prognosis of Hodgkin's disease (HD) has improved during the last 30 years. This study was planned to analyse long-term survival of HD patients and to compare survival rates estimated from clinical trials and population-based data. Individual data were analysed on 2755 adult HD patients entering randomised clinical trials of the British National Lymphoma Investigation (BNLI) between 1970 and 1987, and 5064 patients with HD incident 1978–1984 recorded in the UK population-based cancer registries participating in the EUROCARE study. Relative survival of Hodgkin's disease patients allowing for mortality expected from general population rates was analysed by a proportional hazards regression model including covariates. Although relative mortality decreased with longer follow-up, it was still significantly positive at 9–10 years after diagnosis in both the clinical trials and the population-based data sets. Relative mortality was worse for late stage than for early stage patients even at 10–15 years after first treatment (BNLI data). Whereas 10-year relative survival was identical in trials and population-based patients at ages under 45 years (>69%), it was much higher in BNLI older patients than in the population-based patients. In the older age group (65–74 years) the BNLI patients had 39% relative survival whilst for the population-based patients it was only 27%. Generalisation of clinical trials results to the general population must be done with caution, especially for older patients.

Hematologic Toxic Reaction to Radiation Therapy Adjuvant to Autologous Peripheral Blood Stem Cell Transplantation for Recurrent or Refractory Hodgkin Disease

To evaluate the hematologic toxic reaction to external-beam radiation therapy after high-dose chemotherapy with peripheral blood stem cell (PBSC) support in patients with Hodgkin disease. A retrospective study of 30 cases of Hodgkin disease in patients who underwent high-dose carmustine, etoposide, and cyclophosphamide chemotherapy with PBSC support was performed. Thirteen patients underwent radiation therapy (28.8-39.0 Gy) a median of 45 days after PBSC repeat infusion. Radiation therapy was delivered as planned, without interruption, in all patients. Five patients developed thrombocytopenia (one with grade 1 thrombocytopenia; two, grade 2; and two, grade 3) and included three with progressive disease prior to radiation therapy and two with a history of prior irradiation. None developed a bleeding complication or required transfusion support. Five patients who underwent irradiation had thrombocytopenia (three with grade 1 and two with grade 2) 100 days after PBSC repeat infusion, compared with three patients (two with grade 1 and one with grade 3) who did not undergo posttransplantation irradiation. At the most recent follow-up, no patient without evidence of disease had a platelet count of less than 100 x 10(9)/L. External-beam radiation therapy was well tolerated in the posttransplantation setting in patients with Hodgkin disease. Thrombocytopenia was common but was not related to clinical complications.

Lymphoma discrimination by computerized triple matrix analysis of list mode data from three-color flow cytometric immunophenotypes of bone marrow aspirates

The goal of this study was to evaluate a self-learning algorithm for the computer classification of information extracted from flow cytometric immunophenotype list mode files from high-grade non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). Materials and Methods Bone marrow aspirates (BMA) were obtained from untreated NHL (n = 51), HD (n = 9), or MM (n = 13) patients. Bone marrow aspirates were not infiltrated in NHL and HD patients as confirmed by thorough histologic and cytologic investigation; however, MM patients showed an infiltration rate >50% by malignant myeloma cells. Peripheral blood leukocyte (PBL) samples were taken from age-matched healthy volunteers (n = 44) as easily available control material. A second control group of 15 healthy volunteers, from whom BMA and PBL samples were available, allowed us to differentiate whether the observed classification results on malignant samples were due to the malignant process or simply to the inherent differences between BMA and PBL. Bone marrow aspirates and PBL were analyzed by the same immunophenotyping antibody panel (CD45/14/20, CD4/8/3, kappa/CD19/5, lambda/CD19/5). The acquired list mode data files were analyzed and classified by the self-learning triple matrix classification algorithms CLASSIF1 following a priori separation of the data into a learning set and unknown test set. After completion of the learning phase, known patient samples were reclassified and unknown samples prospectively classified by the algorithm. Highly discriminatory information was extracted for the various lymphoma entities. The most discriminating information was encountered in antibody binding, antibody binding ratios, and relative antibody surface density parameters of leukocytes rather than in percentage frequencies of discrete leukocyte subpopulations. Samples from healthy controls were classified as normal in 97.2% of the cases, whereas those of NHL, HD, and MM patients were on average correctly classified in 80. 8% of the cases. Although no detectable lymphoma cells were present in BMA of NHL and HD patients, the CLASSIF1 classification of the immunophenotypes of morphologically normal cells provided a surprisingly good disease discrimination equal or better than that obtained by examining pathological lymph nodes according to the respective literature. The results are suggestive for a lymphoma-related and disease-specific antigen expression shift on normal hematopoietic bone marrow cells that can be used to discriminate the underlying disease (specificity of unspecific changes), i.e., in this case NHL from HD. Multiple myeloma patients were discriminated by changes on malignant as well as on normal bone marrow cells.

Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma: is there a chance for cure?

To determine differences in prognosis between primary progressive Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients with progressive lymphoma who were treated with different salvage chemotherapy regimens including high-dose chemotherapy (HDCT) followed by autologous stem-cell support (ASCT). One hundred thirty-one patients with primary progressive lymphoma (HD, n = 67; NHL, n = 64) were enrolled. Primary progressive disease was defined as disease progression during first-line chemotherapy or only transient response (complete or partial response lasting </= 90 days) after induction treatment. Patients 60 years or younger with progressive lymphoma were eligible to receive HDCT with ASCT. The overall response rate after salvage chemotherapy for patients with primary progressive HD and NHL was 33% and 15%, respectively. Twenty-five HD patients (37%) received HDCT. Most patients with NHL had progressive disease under salvage treatment, with only six patients (10%) receiving HDCT. Of those, only two patients were alive and in continuous complete remission 3 and 12 months after HDCT. No patient with NHL survived longer than 26 months after first diagnosis. Actuarial OS after 5 years was 19% for all HD patients; 53% for HD patients receiving HDCT, and 0% for patients who did not receive HDCT. In HD patients, multivariate regression analysis identified chemosensitive disease on salvage treatment (P =.0001) and HDCT (P =.031) as significant prognostic factors for freedom from treatment failure. Significant prognostic factors for OS are chemosensitive disease (P =.0005), HDCT (P =.039), and B symptoms at the time of progress (P =.046). There are striking differences in the prognosis of patients with progressive HD and aggressive NHL. The prognosis of progressive NHL patients is dismal. Most patients have rapidly progressive disease after salvage treatment and are, therefore, excluded from HDCT programs. In contrast, progressive HD patients can achieve long-term survival after HDCT.

Hodgkin's disease: Correlation between causes of death at autopsy and clinical diagnosis

The causes of mortality in Hodgkin's disease patients are insufficiently known. Autopsy study is the fundamental procedure in the investigation of these causes. The present study analyzes the autopsies performed in a series of patients diagnosed as having Hodgkin's disease, determining the cause of death in each case and comparing the premortem clinical data and the postmortem findings. A total of 486 patients diagnosed as having Hodgkin's disease between 1967 and 1996 were assessed. Autopsy was performed in 40 of the 144 deceased patients (28%). We reviewed the pathological findings, effects of treatment, discordance between the clinical diagnosis and the outcome of autopsy, and cause of death in each case. The most common clinical causes of death in those patients with autopsy study were tumor progression (37%) and infections (43%) in those patients with autopsy study. The rate of discordance between the clinical and autopsy diagnoses in this study was 43%. The most frequent location of residual Hodgkin's disease was in the lymph nodes. Autopsy study in Hodgkin's disease confirms a high rate of discrepancy between final clinical diagnosis and postmortem lesions despite advances in diagnostic methods. Autopsy revealed causes of death directly related to the treatment, as well as some lesions directly related to patient death and secondary to treatment. Infectious processes are likely to remain undetected and their symptoms can mimic tumor progression.

Viral latent membrane protein 1 (LMP-1)–induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin's and Reed-Sternberg phenotype

AbstractRecently we reported that the down-regulation of CD99 (Mic2) is a primary requirement for the generation of Hodgkin's and Reed-Sternberg (H-RS) cells seen in Hodgkin's disease. In this study, we provide evidence that the down-regulation of CD99 is induced by high expression of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1), which is highly expressed in H-RS cells of EBV-associated Hodgkin's disease. To investigate the effect of LMP-1 on the expression of CD99 in vitro, we established a stable cell line by transfecting an SV40-early promoter driven-LMP-1 expression construct into a neoplastic lymphoblastoid B cell line, IM9, in which the level of endogenous LMP-1 expression is almost negligible. In this cell line, the overexpression of LMP-1 led to the down-regulation of CD99 and the acquisition of morphological and functional characteristics of H-RS cells indistinguishable from those in lymph nodes of Hodgkin's disease patients and in CD99-deficient B cells. In addition, induced LMP-1 expression in an EBV-negative B cell clone, BJAB, directly caused the down-regulation of surface CD99 expression. Northern and Western analysis data, showing that overexpression of LMP-1 negatively influenced the expression of CD99, were supported by experiments in which a CD99 promoter-driven luciferase promoter reporter construct transfected into 293T cells was down-regulated when LMP-1 was coexpressed. Therefore, our data strongly suggest that the EBV LMP-1 protein plays a pivotal role in the down-regulation of CD99 via transcriptional regulation, which leads to the generation of the H-RS cells. (Blood. 2000;95:294-300)

Viral latent membrane protein 1 (LMP-1)–induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin's and Reed-Sternberg phenotype

Recently we reported that the down-regulation of CD99 (Mic2) is a primary requirement for the generation of Hodgkin's and Reed-Sternberg (H-RS) cells seen in Hodgkin's disease. In this study, we provide evidence that the down-regulation of CD99 is induced by high expression of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1), which is highly expressed in H-RS cells of EBV-associated Hodgkin's disease. To investigate the effect of LMP-1 on the expression of CD99 in vitro, we established a stable cell line by transfecting an SV40-early promoter driven-LMP-1 expression construct into a neoplastic lymphoblastoid B cell line, IM9, in which the level of endogenous LMP-1 expression is almost negligible. In this cell line, the overexpression of LMP-1 led to the down-regulation of CD99 and the acquisition of morphological and functional characteristics of H-RS cells indistinguishable from those in lymph nodes of Hodgkin's disease patients and in CD99-deficient B cells. In addition, induced LMP-1 expression in an EBV-negative B cell clone, BJAB, directly caused the down-regulation of surface CD99 expression. Northern and Western analysis data, showing that overexpression of LMP-1 negatively influenced the expression of CD99, were supported by experiments in which a CD99 promoter-driven luciferase promoter reporter construct transfected into 293T cells was down-regulated when LMP-1 was coexpressed. Therefore, our data strongly suggest that the EBV LMP-1 protein plays a pivotal role in the down-regulation of CD99 via transcriptional regulation, which leads to the generation of the H-RS cells. (Blood. 2000;95:294-300)

Value of Transsternal Core Biopsy in Patients with a Newly Diagnosed Mediastinal Mass

Histopathologic analysis of an anterior mediastinal mass of unknown origin is essential for treatment decision. Mediastinoscopy is the most common procedure performed to obtain biopsies, but general anaesthesia and hospitalization are necessary. The aim of this study was to evaluate whether transsternal core biopsies, an easy outpatient biopsy technique, could be an alternative to mediastinoscopy. A biopsy instrument that makes it possible to reach tumours hidden behind bone was used for transsternal CT-guided core biopsies in 21 patients with a newly diagnosed anterior mediastinal mass. No severe side effects were observed. In 19/21 (90%) patients the biopsies were diagnostic. In 2/21 patients additional biopsy techniques had to be used. In these two patients Hodgkin's disease was suspected in the first biopsy procedures. The diagnosis was confirmed by new core biopsies, from other parts of the tumour, not using a transsternal approach (transclavicular and parasternal, respectively). In addition, one mediastinoscopy was performed in a patient who was diagnosed with a non-Hodgkin's lymphoma but where more material was needed for lymphoma subclassification. It is concluded that CT-guided transsternal core biopsy is a clinically valuable method in patients with a newly diagnosed anterior mediastinal mass.

18-FDG-PET for the assessment of residual masses on CT following treatment of lymphomas

The problem of residual masses on post-treatment CT scans is a continuing dilemma for the oncologist treating malignant lymphomas. These masses may contain active disease or represent only necrotic tumour which continues to shrink without further treatment or post-treatment fibrosis which remains stable on continued follow-up. 18-FDG-PET offers a novel metabolic imaging modality, which can differentiate malignant from benign tissue on the basis of increased glycolytic activity. Thirty-two patients (15 with Hodgkin's disease (HD) and 17 with aggressive histology non-Hodgkin's lymphoma (NHL)) who had residual masses on their post-treatment CT scans underwent 18-FDG-PET. The post-treatment CT and PET scans were compared and the accuracy of the 18-FDG-PET in assessing residual masses was evaluated using clinical and pathological follow-up data. Nine patients had positive post-treatment 18-FDG-PET, eight (89%) of whom have relapsed. Twenty-three patients had negative post-treatment PET with only two relapses in this group. The 2 patients who relapsed had aggressive NHL while none of the 11 HD patients with negative PET relapsed. The median follow-up of patients in continued complete remission is 38 months. 18-FDG-PET can differentiate between residual masses containing viable lymphoma where further treatment will be required to achieve cure and those representing ablated disease, where unnecessary treatment and additional morbidity may be avoided.

Analysis by alkaline comet assay of cancer patients with severe reactions to radiotherapy: defective rejoining of radioinduced DNA strand breaks in lymphocytes of breast cancer patients.

Therapeutic exposure to ionising radiation reveals inter-individual variations in normal tissue responses. To examine whether a defect in DNA repair capacity might be involved in such hypersensitive phenotypes, we analysed, using the alkaline comet assay, the response as a function of time to in vitro irradiation at 5 Gy of lymphocytes from 17 breast cancer and 9 Hodgkin's disease patients who developed severe reactions to radiotherapy in comparison with 22 patients with "average" reactions and 24 healthy donors. A difference between breast cancer over-reactors and both patients with normal reactions and healthy donors was observed 30 and 60 min after exposure. A subgroup of breast cancer over-reactors (7/17) reproducibly demonstrated increased levels of residual damage. When the kinetic analyses were prolonged to 120 min, results were in favour of delayed kinetics of rejoining in these patients. Among Hodgkin's disease over-reactors, only one patient showed defective repair. Interestingly, all patients with the most severe complications (grade 4 RTOG/EORTC), i.e., 5 breast cancer and 1 Hodgkin's disease, showed impaired rejoining. Our results suggest that impairment in DNA strand break processing may be associated, in specific subgroups of breast cancer patients, with an individual risk of major toxicity of radiation therapy. Thus, the alkaline comet assay appears to be useful for documenting the DNA repair phenotype in cancer patients.

Long‐term results of 60 patients with pathologic stage I &amp; IIA Hodgkin's disease treated with exclusive mantle radiation therapy

Between January 1972 and December 1982 60 patients with pathological stage IA and IIA Hodgkin's disease (HD) were submitted to Mantle irradiation only. Twenty-five were in stage I (32.1%) and 35 in stage II (67.9%). All patients were submitted to staging laparotomy. Cases with large mediastinal mass were excluded from this series. Delivered doses were 44 Gy in involved areas, 40 Gy on the mediastinum and 36 Gy on uninvolved sites. Twenty-four patients in stage I (96%) and 33 in stage II (94.2%) obtained complete remission. Actuarial 10- and 20-yr overall (OS) rates were 86% and 79.1%, respectively. Event-free (EFS) and relapse-free (RFS) survival rates at 10 and 20 yr were 67.5% and 62.1%, respectively. The occurrence of disease relapse resulted in the only statistical significant prognostic factor for OS in both univariate and multivariate analysis. Distant and extranodal recurrences were significantly (P<0.01) related to a reduced OS. On multivariate analysis stage was the only determinant factor for increased RFS. Extended field RT proved to be an effective curative modality for stage I HD patients, whereas 15 out of 33 patients in stage II relapsed requiring salvage therapy. Long-term analysis of survival and treatment-related morbidity rates will improve our knowledge and assist the physicians to choose the therapeutic option to offer to HD patients.

Effect of Epstein-Barr Virus Infection on Response to Chemotherapy and Survival in Hodgkin's Disease

AbstractWe have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin's disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P = .05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P = .02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P = .18 andP = .40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.