Zsófia Miltényi

Hypothyroidism and thyroiditis after therapy for Hodgkin's disease

During the follow-up of thyroid function of 151 patients with Hodgkin’s disease in complete remission for at least 1 year, 26 cases of subclinical, 12 cases of manifest clinical hypothyroidism and 2 cases of hyperthyroidism (Graves-Basedow disease) were confirmed. Thyroid dysfunction was more frequent in patients who had undergone mantle or neck radiotherapy. Hypothyroidism was most often revealed from the 6th year on following radiotherapy. Thyroid autoantibody positivity was found to be more frequent in patients with thyroid dysfunction, and conversely, thyroid dysfunction was more frequent among the 28 patients with autoantibody positivity. Ultrasound examination and fine needle aspiration cytology of the thyroid confirmed thyroiditis in 96% of the patients with antibody positivity. No relationship was found between thyroiditis and the form of treatment for Hodgkin’s disease. We have found that both neck irradiation and thyroiditis may play a role in the increased number of thyroid dysfunction in patients treated for Hodgkin’s disease. Thyroiditis is not caused by neck radiotherapy but may be the result of immune regulation disorders in Hodgkin’s disease. For substitution or isohormone therapy, levothyroxine is suggested for use. We suggest that examination of the thyroid should be performed at least once a year during the follow-up of Hodgkin’s disease patients.

Epidural malignant lymphomas of the spine: collected experiences with epidural malignant lymphomas of the spinal canal and their treatment.

Study design:Retrospective study of 13 patients treated by the authors.Objective:To examine the course of the disease of malignant lymphoma (ML) presenting in the epidural area of the spine.Setting:Department of Neurosurgery, Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.Subjects and methods:The epidural presentation in eight patients was heralded by motor signs (paraparesis and plegia), in one by a lesion of the posterior columns of the spinal cord (ataxia), and in three by pain. One patient was free of complaints and symptoms. The affected epidural area was diagnosed previously by myelography and computerized tomography (CT), and later by magnetic resonance (MR), over the course of which the location was verified as thoracic in eight patients, cervical in one, and lumbar in four. The authors recommended surgical intervention in 9 out of 13 cases, in seven cases of Hodgkins and six cases of non-Hodgkins lymphoma. Seven patients were treated for recognized manifestations of malignant lymphoma while six were diagnosed by intraoperative-histological examination.Results and conclusion:The decompression operations for tumors resulted in limited improvement in seven patients (reduction in pain and return of ability to walk). Four patients were not operated on, two of which had significant improvement in their neurological symptoms. Paraparesis remained unchanged in one patient. One patient remained symptom-free. The authors emphasize the importance of interdisciplinary consultation and weighing individual priorities in the indications for operation on epidural ML.

Mediastinal Bulky Tumour in Hodgkin’s Disease and Prognostic Value of Positron Emission Tomography in the Evaluation of Post-Treatment Residual Masses

Among the 193 patients (82 female, 111 male) treated primarily for Hodgkin’s disease at our clinic between 1990 and 2001 and followed up until 2003, 42 (22%) had mediastinal bulky tumours (MBTs) by the Cotswolds criteria. The rate of MBT diagnosis was significantly greater in the early stage of the disease, these patients were younger and – in contrast to the other group – they all received combined therapy. No significant differences were found in the overall and relapse-free survival rate in the two groups, but relapse and death rates were lower in the patients with bulky tumours. Of the total number of patients, 27 underwent a total of 31 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) examinations, mainly for the evaluation of post-treatment residual mass viability. In the 12 positive cases, the majority of patients received further therapy. During the mean follow-up time of 58 months (range 5–98 months) after obtaining negative results, progression of the disease was found in 2 cases 14 and 23 months later, respectively. Based on our results, we conclude that FDG-PET examinations show a good correlation with clinical follow-up results.

Quality of life and fatigue in Hodgkin's lymphoma patients.

Aims and background Quality of life and survival of patients with malignant diseases are improving thanks to the development in diagnostics and therapy. Methods We determined the quality of life and frequency and severity of fatigue with an EORTC QLQ-C30 questionnaire in 168 Hodgkins lymphoma patients (85 women, 83 men). We scored all functional and symptom scales in cured patients (who were in complete remission for at least 10 years; mean period of survival after the treatment(s) was 16.61 years) and in those who suffered from late complications. Results The global health status score (QL2) was significantly lower in patients who had late complications (mean QL2, 45.53) than in patients with no complications (mean QL2, 67.57, P <0.001) and in cured patients (mean QL2, 52.5) than in those who were not disease free 10 years after the treatment or who were treated actively (mean QL2, 67.48, P <0.001). We found that fatigue level (FA) was significantly higher in patients who had been treated more than 20 years before (FA score, 53.37) than in those who were undergoing treatment (FA score, 29.35, P = 0.03). A significantly higher FA score (FA, 48.72) was observed in patients who suffered from late complications of the treatment than in those who had no complications (FA, 31.88; P = 0.001). More co-morbidity can cause higher fatigue scores than observed in these groups of Hodgkins lymphoma patients. Conclusions Fatigue is more frequent than we think, and it has a strong effect on quality of life, so its early recognition and treatment is important and needs multidisciplinary cooperation.

Association between the epstein-barr virus and hodgkin's lymphoma in the north-eastern part of Hungary : Effects on therapy and survival

This retrospective study included 109 patients with Hodgkin’s lymphoma (HL; 45 females, 64 males). In 47 of the 109 HL patients (43%), immunohistochemical analysis of their formalin-fixed, paraffin-embedded histologic samples revealed Epstein-Barr virus (EBV) by latent membrane protein (LMP) 1. The highest virus association (50%) was found with the mixed cellularity histologic subtype, especially in patients aged 11–20 and >50 years. Virus positivity in nodular sclerosis was 35% (negative cases accumulated in patients aged 15–30 years). Regarding clinical stages, histologic subtypes, general symptoms, treatments employed and response to treatment, the EBV-positive group was not significantly different from the virus-negative group. During the mean follow-up time of 83 months (9–300 months), the overall or event-free survival of EBV-negative patients was more favorable than that of EBV-positive patients, although the difference was not significant (p = 0.16 and p = 0.24, respectively). EBV infection may be involved in the pathogenesis of HL in our Hungarian study cohort, but it does not significantly affect clinical symptoms, therapeutic results or complete and event-free survival of HL patients.

HCV and HGV infection in Hodgkin's disease.

Numerous observations imply that the pathogenesis of malignant lymphomas is multifactorial and that viruses probably play an important etiologic role. Besides Epstein-Barr virus, there might be other viruses among the causes of Hodgkin’s disease. A total of 111 randomly selected patients with Hodgkin’s disease were included in this study, and hepatitis C and G viruses were tested with polymerase chain reaction. The results were compared to hepatitis C and G virus infection ratios assessed by polymerase chain reaction in the Hungarian blood bank. Hepatitis C virus was diagnosed in 10 (9%) patients, and hepatitis G virus in 9 (8,1%), which is a 12-fold and a 1,5-fold infection rate as compared to that of the Hungarian blood bank, respectively. There was no significant difference between hepatitis positive and negative patients concerning mean age at the time of diagnosis, sex, disease stage, histology type, treatment applied, risk factors in the history of the infection and liver enzymes. Hepatitis C virus positivity in patients with Hodgkin’s disease differs significantly from that in blood donors. Based on these results and data in the literature, no definite statement can be made on the etiological role of viruses, but further studies are needed.

Brentuximab vedotin for treating Hodgkin’s lymphoma: an analysis of pharmacology and clinical efficacy

Introduction: Hodgkin’s lymphoma (HL) is a highly curable lymphoma with a 70 – 90% long-term survival; however, patients with relapsed or refractory disease may need additonal therapies and have significantly worse prognosis. Brentuximab vedotin (BV) is an anti-CD-30 antibody-drug conjugate, which was approved for treating classical HL patients following autologous stem cell transplantation or failure of at least two prior multi-agent chemotherapies within a year. Areas covered: Current clinical trials are investigating the role of BV in frontline, salvage and adjuvant setting of treatment. Safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues of BV are also discussed. Expert opinion: BV is a targeted therapeutic option for treating HL, which is a significant improvement compared to conventional multiagent chemotherapy. It may represent a valid option for heavily pretreated patients. Currently running clinical trials are seeking a role for BV in the first-line setting, as well as treating autologous stem cell transplant candidate patients, relapsing after autologous stem cell transplant, bridging to allogenic stem cell transplant and treating elderly patients. Indication of drug may change, expand and an exact role may be established in the upcoming 5 years based on the results of currently running trials.

Rare association of Hodgkin lymphoma, Graves’ disease and myasthenia gravis complicated by post-radiation neurofibrosarcoma: coincidence or genetic susceptibility?

With Hodgkin lymphoma (HL), other (autoimmune) diseases may occasionally occur or associate, whereas as a late treatment-complication, second tumour may develop. In our patient HL was diagnosed in 1996 and consequently received COPP/ABV and mantle irradiation. Due to the residual mediastinal tumour CRu was declared but later on no progression/relapse could be proved by PET. In 2000 Graves’s disease, in 2001 myasthenia gravis was diagnosed, which showed resistance for immunosuppressant drugs, thus plasmapheresis, intravenous immunoglobulin treatments were applied. In 2005, the residual mediastinal tumour started progressive growth, which leads to thoracotomy in which the tumour was removed, it was malignant peripheral nerve sheath tumour. The disease showed progression despite the chemotherapy applied and the patient died in 2007 due to respiratory failure. Not even the postmortem histopathologic examination revealed the relapse of HL. Association of Hodgkin lymphoma, and two antibody-mediated autoimmune diseases, Graves’ disease and myasthenia gravis, is rare and has not yet been reported in the literature. The etiologic role of genetic predisposition and immune regulatory disorder must definitely be thought of, as the possibility of mere coincidence is extremely small. Malignant peripheral nerve sheath tumour is a rare complication of irradiation, which underlines the importance of the risk or/and response adapted therapy of HL.

Epidural involvement in Hodgkin's disease

Epidural involvement is analyzed retrospectively in 512 patients with primary treatment and follow up for Hodgkins disease (HD) between 1970 and 1999. In one case (0.2%) epidural manifestation was the first symptom and in six cases (1.2%) it occurred later, at a disseminated, advanced stage. All seven patients were male: three had mixed cellularity and four nodular sclerosis histological subtype. The thoracic segment was involved in four cases, the lumbar in two and the cervical segment in one case. The most frequent symptoms were back pain, limb weakness, paresis/plegia, incontinence. Computer tomography, magnetic resonance imaging and myelography were used as diagnostic procedures and in planning the treatment. Functional recovery was achieved by laminectomy, loco-regional irradiation and adjuvant polychemotherapy with remission of HD for 6-100 months. Later, however, six patients died due mainly to relapse/progression of HD. We emphasize the importance of an interdisciplinary approach in the treatment of HD with this relatively rare appearance, which requires close co-operation among oncohematologists, neurologists, radiologists, neurosurgeons, radiotherapists and physiotherapists.

Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced toxicity.

Introduction: Survival of Hodgkin lymphoma (HL) patients has significantly improved in recent decades. The current first-line therapy is doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) ± irradiation and may cause pulmonary toxicity. Strategies to reduce late toxicity as well as increase survival rate are of interest. Patients and methods: Pulmonary function of previously treated HL patients was collected over a 12-month period using St. George Respiratory Questionnaire (SGRQ), chest X-ray, dynamic inhalation lung scintigraphy and spirometry. Results: A total of 137 patients’ data were reviewed. Median time elapsed since diagnosis was 11 years (range was 2 – 30 years). Chest irradiation did not significantly worsen pulmonary function. Number of ABVD cycles with consequential bleomycin dose showed significant correlation with SGRQ total score in patients receiving ABVD plus chest irradiation (p = 0.01). Scintigraphy results correlated with bleomycin dose in patients receiving ABVD without chest irradiation (right side: p = 0.099, left side: p = 0.051). Discussion: An additive negative effect of chest irradiation was not confirmed as reflected in the literature; however, increasing cumulative bleomycin dose worsened pulmonary function.