[What is actually Hodgkin disease?]. / Hva er egentlig Hodgkins sykdom?

For long, there has been controversy over the very nature of Hodgkin's disease: Is it a true neoplasm, an inflammatory, even infectious disease, an unusual immunologic reaction, or a combination of these pathogeneses? New information has been obtained during the last few years from immunohistology, immunohistochemistry, and molecular genetics. Epidemiologic, serologic and and direct detection studies all independently point to Epstein-Barr-virus as a potential aetiologic cofactor. Clonality studies show that viral infection precedes clonal expansion of tumour cells. Single cell analysis of rearrangement of immunoglobulin genes published 1996-98 proves the B cell nature of Reed-Sternberg and Hodgkin cells, and indicates their origin from a single transformed B cell and subsequent monoclonal expansion. Hodgkin's disease is a tumour of cytokine-producing and cytokine-responding cells. Different quantities of a series of cytokines may explain differences in prognosis, clinical symptoms and histopathological features.

[Acute myelogenous leukemia and myelodysplastic syndrome after treatment with cytostatic agents]. / Akutt myelogen leukemi og myelodysplastisk syndrom etter cytostatikabehandling.

INTRODUCTION: The introduction of high dose chemotherapy of cancer has been followed by an increased incidence of therapy-related acute myeloid leukaemia and myelodysplastic syndrome. MATERIAL AND METHODS: A survey of the literature has shown that these complications have been attributed to a high accumulated dose of alkylating agents, antracyclins and epipodophyllotoxins. The incidence increases after additional irradiation. RESULTS: After standard doses of leukaemogenic drugs the incidence of acute myeloid leukaemia and myelodysplastic syndrome is reported to be 0-4%, increasing to 8-10% after high dose therapy. At diagnosis of acute myeloid leukaemia and myelodysplastic syndrome, most of the patients have chromosomal abnormalities. INTERPRETATION: The prognosis of therapy-related acute myeloid leukaemia and myelodysplastic syndrome is poor compared to that in primary acute myeloid leukaemia and myelodysplastic syndrome.

[Cancer and religiosity--a follow up of patients with Hodgkin's disease]. / Kreft og religiøsitet--en etterundersøkelse av pasienter med Hodgkins sykdom.

In this study of religiosity among cancer patients and the relationship between religiosity and illness, a questionnaire was sent to 183 survivors of Hodgkin's disease in November 1995, all of them patients treated at the Norwegian Radium Hospital between 1988 and 1994. 107 patients (58%) gave replies to 45 questions relating to religion and belief, view of life, quality of life, and the relationship between religiosity and illness. The patients' attitude to religion differed little from that of the Norwegian population at large. 15% of the patients defined themselves as atheists, 14% as agnostics, 23% believed in God as an impersonal supreme power, and 48% in a personal God. 40 patients (38%) had changed their religious belief, 33 of them becoming more religious. 58% had prayed to God (or a supreme power) for cure. Half of the respondents felt that their religious belief had been a support during their illness. 52 (49%) were not satisfied with the pastoral services during hospitalisation. The study indicates that cancer disease activates religiosity, and that religiosity may help patients cope with their disease.

Fatigue and psychiatric morbidity among Hodgkin's disease survivors.

Fatigue is prevalent among cancer patients, including Hodgkin's disease survivors (HDS). Fatigue is poorly understood, and the clinical management is consequently difficult. This cross-sectional study examined how fatigue related to psychiatric morbidity among 457 HDS (aged 19-74 years, 56% males) treated during the period 1971-1991. The subjects were mailed a questionnaire including the Fatigue Questionnaire, the Hospital Anxiety and Depression Scale, and measures of previous psychiatric problems. Fatigue correlated moderately with anxiety and depression (r = 0.44 and 0.41 respectively). Twenty-six percent of the HDS had substantial fatigue for 6 months or longer (=cases). They had higher levels of anxiety (mean 7.3, 95% CI 6.4-8.1) and depression (mean 4.5, 95% CI 3.8-5.2) than the non-cases (anxiety: mean 4.3, 95% CI 3.9-4.7; depression: mean 2.1, 95% CI 1.8-2.5). Past psychiatric problems were not reported more commonly among the fatigue cases than among the non-cases. A multiple logistic regression analysis identified age (OR 1.04, 95% CI 1.02-1.06), anxiety (OR 1.2, 95% CI 1.2-1.3), and no self-reported psychiatric symptoms during treatment (OR 2.3, 95% CI 1.3-4.2) as predictors of fatigue caseness. One-half of the fatigue cases among HDS have psychological distress that might respond to treatment. Chronic fatigue among HDS is not predicted by previous psychiatric problems.

Hodgkin's disease survivors more fatigued than the general population.

PURPOSE: To estimate the level of fatigue and frequency of fatigue cases among Hodgkin's disease survivors (HDS) and compare them with normative data from the general population. PATIENTS AND METHODS: A cross-sectional follow-up study was done of 557 HDS (age range, 19 to 74 years) treated at the Norwegian Radium Hospital from 1971 to 1991. The sample was approached by mail, and their data were compared with normative data from 2,214 controls (age range, 19 to 74 years) representative of the general Norwegian population. Of the 557 HDS, 459 (82%) responded. The mean age (+/- SD) at the time of study was 44+/-12 years, and the mean observation time was 12+/-6 years. The Fatigue Questionnaire (11 items) measures physical and mental fatigue. Two systems of scoring were used, dichotomized (0, 0, 1, and 1) and Likert (0, 1, 2, and 3). Total fatigue (TF) constitutes the sum of all the Likert scores. Caseness was defined as a total dichotomized score of > or =4 and fatigue that lasted 6 months or longer. RESULTS: The HDS had significantly higher levels of TF than the controls (14.3 v 12.2) (P < .001). Fatigue among the HDS equaled that of the controls in poorest health. More HDS (61%) than controls (31%) reported fatigue symptoms lasting 6 months or longer (P < .001). Fatigue cases were more frequent among HDS (men, 24%; women, 27%) than among the controls (men, 9%; women, 12%) (P < .001). Disease stage/substage IB/IIB predicted fatigue caseness (P = .03). No significant associations were found between treatment characteristics and fatigue. CONCLUSION: Hodgkin's disease survivors are considerably more fatigued than the general population and report fatigue of a substantially longer duration.

Late medical sequelae after therapy for supradiaphragmatic Hodgkin's disease.

A total of 221 consecutive early stage Hodgkin's disease (HD) patients were given mantle field irradiation only or in combination with chemotherapy in 1971-1991. In 1994 these patients responded to a mailed self-report questionnaire covering items on late medical symptoms. Of 200 patients (91%) who reported that their thyroid function had been tested, 110 patients (55% of those tested) had thyroid hypofunction at follow-up in 1994. Ninety-five patients (86% of patients with biochemical hypothyreosis) had started hormonal substitution. In 1993 and 1994, 101 of these patients who had received mantle field irradiation in 1980-1988 were called in for interview, clinical examination and thyroid function tests. Eighteen patients (18%) had started hormonal substitution treatment earlier, but 58 (70%) of the other 83 patients were found to have biochemical hypothyreosis. Of the 221 patients who completed the questionnaire, 66 patients (30%) reported dyspnoea on exertion for more than 3 years after treatment, 8 patients (4%) reported a history of myocardial infarction, 6 patients (3%) reported pericardial disease and 25 patients (11%) heart valve disease. Increased expenses incurred for dental care were reported by 106 patients (48%), increasing to 55% when Waldeyer's ring had been irradiated. The consequences of late sequelae after mantle field irradiation for future treatment are discussed.

[Late complications after treatment of Hodgkin's disease]. / Senkomplikasjoner etter behandling for Hodgkins sykdom.

Treatment of Hodgkin's disease involves chemotherapy and radiation. Both modalities may cause cardiac, pulmonary and thyroid side-effects. In a cross-sectional study, we aimed to assess the occurrence and severity of such complications. From 1980 to 1989, 129 Norwegian patients (< 50 years old) had curative treatment for Hodgkin's disease 116 (90%) of them participated in the study (follow-up period 5-13 years). Methods included lung function tests, chest X-rays, bicycle exercise tests, echocardiography and thyroid function tests. Nearly 30% of the patients reported dyspnoea on exertion and had associated reductions in lung function. Evidence of fibrosis occurred in 68%, but was associated with reduced lung function in only 12%. Pathological left-sided heart valve regurgitations were detected in 24% of the patients, pericardial thickening in 15%, and coronary artery disease in 5%. Biochemical hypothyreosis was found in 67% of the patients. We conclude that cardiac, pulmonary and thyroid dysfunctions are frequent long-term side-effects after treatment for Hodgkin's disease. We recommend annual screening of thyroid function and echocardiographic examination in patients who have received standard mantle field radiotherapy without cardiac shielding. Lung function testing should be done in individuals who require further radiation, chemotherapy or thoracic surgery.

Reduced health-related quality of life among Hodgkin's disease survivors: a comparative study with general population norms.

BACKGROUND: Late complications after curative treatment of Hodgkin's disease are of special relevance because most of the cured are young adults. The aims of the present study were: (1) to compare health-related quality of life (HRQOL) in Hodgkin's disease (HD) survivors with normative data from the general Norwegian population and (2) to examine the relations between disease/treatment characteristics and HRQOL in the HD survivors. PATIENTS AND METHODS: 459 HD survivors aged 19-74 years (mean 44.0, SD 11.8) treated at the Norwegian Radium Hospital 1971-1991 were approached in 1994 and compared to norms from 2214 subjects approached in 1996. The norms are representative of the general Norwegian population. HRQOL was assessed by the Short Form 36 (SF-36), which measures HRQOL in eight separate scales (0 = worst health state, 100 = best health state). RESULTS: The HD survivors had lower scores than the normal controls on all scales after adjustment for age, gender and educational levels. Statistically significant differences (P < 0.01) were found in general health (10.4), physical functioning (6.1), role limitations (physical, 9.3), physical functioning (3.6) and in vitality (4.7). Patients with disease stage IB-IIB had the lowest scores on all scales. The differences in relation to stage/substage reached statistical significance (P < 0.01) in physical functioning and in role limitations (physical). Time since diagnosis, types of primary treatment or having relapsed were not associated with statistically significant differences in HRQOL. CONCLUSION: Long-term HD survivors have poorer HRQOL, primarily in physical health, than the general Norwegian population.

Socio-medical situation for long-term survivors of Hodgkin's disease: a survey of 459 patients treated at one institution.

We present the socio-medical situation for 459 adult disease-free long-term survivors of Hodgkin's disease (HD) 3-23 years after first line curative treatment. In 1994, 557 patients were sent a self-report questionnaire relating to their social status and 459 patients (82%) replied. Educational or professional plans were changed due to HD in 142 patients (32%). After 6, 12 and 18 months from start of treatment, 52, 82 and 95% of the patients, respectively, had returned to their job or education. The sum of full-time and part-time employment was in men 78% at diagnosis and 85% at follow-up, and in women 57% at diagnosis and 64% at follow-up. Only 2% of men and 3% of women did not have a job at follow-up in 1994. At diagnosis 2% of the patients were permanently disabled versus 19% at follow-up in 1994. Age > 40 years at diagnosis, increased the total score of psychological distress and fatigue and long-term disablement after first line treatment were predictors for permanent disablement. Transient or permanent sexual problems were reported in 16% and 13%, respectively. MVPP (mustine, vinblastine, procarbazine and prednisone) or LVPP (chlorambucil, vinblastine, procarbazine and prednisone) chemotherapy was responsible for most cases of early menopause in women older than 30 years, and of infertility in both men and women. In summary, most long-term HD survivors had adapted well to their socio-medical situation except a high number of permanently disabled patients. By focusing more on factors predisposing for permanent disablement and early treatment for these, more patients may be helped to return to their job.

Psychological distress after cancer cure: a survey of 459 Hodgkin's disease survivors.

To assess the levels of psychological distress and identify predictors of anxiety/depression caseness after cancer cure, a national population of 557 Hodgkin's disease (HD) survivors was surveyed. The respondents [204 women, 255 men, mean age 44 years (SD = 12)] returned a mailed questionnaire including The Hospital Anxiety and Depression Scale (HADS). Disease and treatment variables were based on the hospital records. A total of 27% had caseness scores (anxiety, 14.5%; depression, 4%; anxiety and depression, 8.5%). In a multiple logistic regression analysis, anxiety caseness was predicted by low educational status [OR (odds ratio) = 2.07, 95% CI = 1.02-4.22], observational period 7 years or longer (7-10 years: OR = 3.07, 95% CI = 1.26-7.47), combined irradiation and chemotherapy treatment (OR = 2.77, 95% CI = 1.17-6.54) and psychiatric symptoms before HD (OR = 2.55, 95% CI = 1.40-4.65) or during treatment (OR = 3.51, 95% CI = 2.08-5.90). Depression caseness was predicted by age (OR = 1.03, 95% CI = 1.00-1.06) and psychiatric symptoms before HD (OR = 5.1, 95% CI = 2.55-10.31) Anxiety cases are more prevalent than in the general Norwegian population, and were found to be most common 7-10 years after treatment. The most intensive treatment was associated with increased risk for anxiety caseness. The subjects experienced distress during treatment precedes difficulties in long-term adjustment. Focusing on these predictors during treatment and follow-up controls may improve long-term outcome.

Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin's disease: an echocardiographic study.

OBJECTIVE: To assess by echocardiography the occurrence and degree of late cardiac sequelae after treatment for Hodgkin's disease by radiation and chemotherapy. PATIENTS AND METHODS: In Norway from 1980 to 1988, 129 patients < 50 years old with Hodgkin's disease had curative treatment with mediastinal radiation, with or without chemotherapy. 116 (90%) of these patients (mean (SD) age 37 (7) years, 67 males) were examined by echocardiography 5-13 years after treatment. 40 healthy individuals (mean (SD) age 40 (11), 20 males) were examined as controls. All those examined were in regular sinus rhythm. RESULTS: Grade > 1 (scale 0-3) aortic and/or mitral valvar regurgitation was found in 24% of the patients (15% aortic, 7% mitral, and 2% aortic+mitral), affecting 46% of the females v 16% of the males (P < 0.001). Female gender was a significant risk factor for aortic and mitral regurgitation (odds ratio 4.7, 95% confidence interval 2.0 to 11.2), whereas age, period of follow up, radiation dose, and chemotherapy were not. Thickened pericardium was diagnosed in 15% of the patients. No risk factors were identified. No cases of pericardial thickening or valvar regurgitation grade > 1 were recorded in the control group. Mean values for measured and calculated indices of systolic and diastolic function were within the normal range for patients and controls. The patients had reduced E/A ratio compared with the healthy controls (E/A 1.1 v 2.0, P < 0.001). CONCLUSIONS: Abnormal left sided valvar regurgitation was detected in one fourth of the patients, affecting the aortic valve in more than half of the cases. Females had an increased risk of valvar regurgitation. Echocardiographic screening after high-dose mediastinal radiation is recommended.

Cardiopulmonary sequelae after treatment for Hodgkin's disease: increased risk in females?

BACKGROUND: The treatment of Hodgkin's disease (HD) involves irradiation and chemotherapy. Both modalities may cause heart and lung injury. We aimed to assess 1) the occurrence of such injury, 2) the extent to which combined versus single-organ-affection resulted in disability, and 3) whether determinants for cardiopulmonary injury could be identified. PATIENTS AND METHODS: A national cohort (n = 116) of HD patients (mean age 37 +/- 7 (SD) years, 67 males) was examined by interview, echocardiography, bicycle exercise test and lung function tests, 5-13 years after mediastinal irradiation with or without chemotherapy. RESULTS: Cardiac, pulmonary or combined sequelae occurred, respectively, in 21%, 15% and 19% of the patients affecting 75% of the females versus 41% of the males (P < 0.001). Of the patients with combined sequelae, 27% were disabled versus 4% of the rest (P < 0.05). Combined sequelae was associated with dyspnoea (P < 0.001) and reduced maximal exercise heart rate (P < 0.05). Compared to males, females had an increased risk of heart valve regurgitation (46% versus 16%, P < 0.001), pericardial thickening (22% versus 10%, P = 0.07) and reduced gas transfer (41% versus 22%, P = 0.03). Female gender was a significant risk factor for cardiac and/or pulmonary sequelae (OR 6.1, 95% CI 2.4-15.7), whereas age, follow-up period, smoking habits, histology, bulky mediastinal disease, radiation dose and chemotherapy were not. Mean exercise work capacity and O2-saturation were within normal limits. CONCLUSIONS: Although cardiac and/or pulmonary sequelae were detected in more than half of the patients, only combined injury was associated with disability, dyspnoea and reduced performance. Females had an increased risk of cardiopulmonary sequelae, which could not be explained by treatment-related differences between the genders.

Clinical stage I and II Hodgkin's disease: long-term results of therapy without laparotomy. Experience at one institution.

BACKGROUND: We concluded a program in which we administered radiotherapy only to clinical stages I and II Hodgkin's disease patients at standard risk, with the addition of 4 cycles of combination chemotherapy before radiotherapy for high-risk patients. PATIENTS AND METHODS: From 1980 to 1991, 313 patients with clinical stages I or II Hodgkin's disease underwent treatment in our hospital. Fifty percent of the patients in groups previously identified as being at high risk for relapse received 4 cycles of combination chemotherapy before radiotherapy. The remaining half of the patients received radiotherapy only. RESULTS: Low- and high-risk patients aged 15-59 years had, respectively, complete remission (CR) rates of 97% and 94%, 5-year survivals of 95% and 91%, and 5-year freedom from relapse (FFR) rates of 78% and 89%. Older low- and high-risk groups had CR rates of 97% and 93%, 5-year survivals of 60% and 56% and 5-year FFR of 77% and 93%, respectively. CONCLUSION: Here we present our favorable results after treating standard-risk patients with clinical stages I and II Hodgkin's disease with radiotherapy only. With the addition of chemotherapy, the rate of relapse in the high-risk patients was reduced below that of the standard-risk patients. Overall survival was the same for the high- and standard-risk patients.

Prognostic variables and results of salvage treatment in Hodgkin's disease.

Treatment results and prognostic variables were studied in 549 adult patients with Hodgkin's disease after first-line and salvage treatment. After first-line treatment, 479 out of 549 patients (87%) achieved complete remission (CR). During a mean observation time of 74 months, 99 patients (21%) relapsed. Sixty-nine patients (70% of relapsed patients) achieved a second CR. Variables predicting poor response (< CR) and shortened survival after first-line treatment were advanced disease, B-symptoms and age >60 years. In relapsing patients, age >60 years, relapse within 12 months and non-CR after relapse treatment predicted a poor prognosis, and none of these patients were alive after 10 years. Localized disease at diagnosis and relapse, and relapse later than 24 months predicted a good prognosis with 10-year survival after relapse of 68% and 57%, respectively. Patients with a second relapse had 5-year survival of 28% and 10-year survival of 14%. Based on the prognostic variables at first-line treatment and at relapse, selection of patients to more intensive treatment is discussed.

ChlVPP is as effective as alternating ChlVPP/ABOD in advanced stage Hodgkin's disease.

The purpose of the study was to evaluate and compare the efficacy and tolerability of two cytostatic regimens-chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) vs. ChlVPP alternating with doxorubicin, bleomycin, vincristine and dacarbazine (ABOD). One hundred eligible patients with stage IIIA-IVB Hodgkin's disease were randomized to either ChlVPP or ChlVPP alternating with ABOD. The complete response rate (CR) was 80% in both treatment groups. After a median follow-up time of 59 months, 42 (84%) of the patients in the ChlVPP-treated group were in CR compared with 39 (78%) treated with ChlVPP/ABOD. The estimated five-year overall and relapse-free survival rates were 87% and 74%, respectively, for the ChlVPP-treated patients and 76% and 73% for the ChlVPP/ABOD-treated patients. The ChlVPP regimen showed a slightly better subjective tolerance than the ChlVPP/ABOD regimen. The given dose intensity was very close to optimal, and equal for the two regimens.

Lung function impairment in long-term survivors of Hodgkin's disease.

BACKGROUND: Treatment of Hodgkin's disease (HD) involves radiation and chemotherapy, modalities known to cause lung injury. PATIENTS AND METHODS: In Norway, between 1980 and 1988, 129 patients aged less than 50 years at the time of diagnosis, had curative treatment with thoracic radiation alone or combined-modality therapy for supradiaphragmatic HD. We have examined 116 (90%) of these patients by interview, chest X-ray and lung function tests, 5-13 years after treatment. RESULTS: Nearly 30% of the patients had dyspnoea on exertion and associated reductions in total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and gas transfer (TLCO) (p < 0.05). Radiographic evidence of no, slight or moderate fibrosis occurred in 32%, 54% and 14% of the patients, respectively. Moderate fibrosis was associated with reductions in FVC, FEV1 and TLCO (p < 0.05). Radiation plus chemotherapy containing bleomycin-anthracyclines (median cumulative bleomycin dose 120 mg) was associated with decreases in FVC and TLCO (p < 0.05). In the multivariate analysis, chemotherapy with bleomycin-anthracyclines was the only significant predictor for lung function impairment. CONCLUSION: More than five years after therapy, respiratory symptoms and reduction in lung function were diagnosed in nearly one-third of otherwise healthy HD survivors.

Magnetic resonance imaging and 67gallium scan in mediastinal malignant lymphoma: a prospective pilot study.

BACKGROUND: A residual mediastinal mass is common after treatment for bulky mediastinal lymphoma and represents a difficult diagnostic problem. PATIENTS AND METHODS: 19 patients with bulky mediastinal masses due to malignant lymphoma had computed tomography (CT), magnetic resonance imaging (MRI) and 67Gallium scan (67Ga) before treatment, after four cycles of chemotherapy, and two, six and twelve months after end of treatment. RESULTS: MRI and 67Ga showed active tumor in all patients before treatment. Twelve months after treatment full consistency was found between the results of the two techniques. During treatment and the first six months after treatment, the two techniques were not in accord in some patients, partly due to later normalization of MRI compared with 67Ga. CONCLUSION: Both MRI and 67Ga are useful in assessing tumor activity in lymphoma mediastinal masses.

[Hodgkin's disease or lymphogranulomatosis. New views on prognosis, complicating conditions and complications after treatment]. / Hodgkins sykdom eller lymfogranulomatose. Nyere synspunkter på prognose, følgetilstander og komplikasjoner etter behandling.

Between the years 1968-85, 1,177 patients started treatment for Hodgkins disease at the Norwegian Radium Hospital. In this unselected material from Norway the age distribution was bimodal with the highest incidence between 20-40 years of age. Survival is dependent on age, stage and histology, and was better between the years 1980-85 as compared with the period 1974-79. During the last ten years, treatment has been decentralized in Norway, and all centres cooperate by using the same protocol for staging and treatment. The article summarizes the results of the treatment, and related complications.

[New cancer disease after treatment of Hodgkin's disease]. / Ny kreftsykdom etter behandling for Hodgkins sykdom.

The risk of a second cancer was assessed in 1,152 patients with Hodgkins disease who were treated at the Norwegian Radium Hospital from 1968-85. 68 patients developed a second cancer more than one year after the diagnosis of Hodgkins disease. These included nine acute non-lymphocytic leukemias, eight non-Hodgkins lymphomas and 51 solid tumours, including 11 lung cancers. The overall relative risk (observed/expected ratios) of developing a second cancer was 1.86. After 18 years the cumulative risk of developing a second cancer was 14.4% +/- 2.9%, of which 11.2% +/- 2.6% referred to solid tumours. The cumulative risk of leukemia appeared to reach a plateau level of 1.5% after 12 years while the risk of non-Hodgkins lymphomas and lung cancer continued to rise with time to 2.1% and 3.3% respectively after 18 years. The risk of developing leukemia increased after treatment with alkylating agents and Procarbazine. The risk of non-Hodgkins lymphoma was not related to any specific type of therapy. Excess lung cancer risk was noted in patients treated with radiotherapy, and the cancers appeared within the treated areas.