[Relapse in Hodgkin's disease. Incidence of relapse in a group of 374 patients from 1 June 1968 to 31 March 1995]. / Relaps Hodgkinovy choroby. Incidence relapsu v souboru 374 nemocných v období od 1. 6. 1968 do 31. 3. 1995.

From a group of 366 patients with complete data complete remission was achieved by 290. Fifty-five patients relapsed, 39 men and 16 women, mostly with an initial finding of advanced disease (KS III + IV 64%), with affection of the mediastinum (73%) aged under 40 years. 42% of the relapses were detected within one year after termination of primary treatment and 33% during the subsequent 2 years, the longest interval before a relapse being 20 years. During primary treatment in 63% of the patients chemotherapy was reduced to 75-25% of the total dose of cytostatics with protraction of the interval between cycles in 58% and radiotherapy in another 34% of the patients. 76% of the patients with a first relapse achieved a second complete remission and 29 of them survive without signs of the disease, 12 died from generalized lymphoma. Sixteen patients developed repeated relapses (nine two relapses, four three relapses, another two four relapses and one patient five relapses). After treatment of the relapse a total of 22 patients died, incl. 19 who died from Hodgkin's disease, two from secondary carcinoma and one from myocardial infarction. The longest survival period after treatment of a relapse was 26 years.

[The significance of mediastinal involvement and other risk factors for survival in patients with Hodgkin's disease]. / Význam postizení mediastina a dalsích rizikových faktoru pro prezití nemocných s Hodgkinovou chorobou.

The impact of prognostic factors for survival was analyzed in a group of 337 patients with Hodgkin's disease. The analysis of survival of patients comprised a total of 13 indicators: histological types LP, NS, MC, LD, clinical stages I, II, III, IV, E lesions, symptomatology A, B, size of the mediastinal tumour (index), age at onset of disease and sex. Cumulative survival of 5, 10, and 20 years in the whole group is 83%, 80% and 72% resp. A first complete remission was achieved by 284 patients, cumulative survival without the disease is 79% after 5 and 73% after 10 years since completion of primary treatment. A significantly adverse effect on the prognosis of survival is exerted by symptomatology B, a large mediastinal tumour, advanced age, clinical stage IV and III. Most important are the first two factors mentioned. An adverse prognostic factor for survival without disease is male sex. The therapeutic protocol was repeatedly modified in the course of 25 years with regard to prognostic patient groups.

[Pulmonary complications and their prevention in the treatment of Hodgkin's disease]. / Plicní komplikace lécby u Hodgkinovy choroby a jejich prevence.

Pulmonary ventilation was monitored in a group of 102 patients with Hodgkin's disease. In the initial finding a tendency of a restrictive disorder is apparent (43% of the patients) with the increasing size of the mediastinal tumour (79% mediastinal patients with a bulky finding in 40%), without statistical significance. After treatment a restrictive disorder was recorded in 35% of the patients with a normal initial finding and conversely normalization of results occurred in 12% patients with a pathological result of the spirometric examination. After a one-year interval the finding deteriorated in 12 % of the patients without post-treatment disorders of pulmonary ventilation and in 15% the assessed disorder receded. Statistical analysis did not reveal a significant relationship between the results of spirometry and bleomycin treatment. 77 patients were examined after an interval of 2, 3, 4 and more years following termination of primary treatment without a significant correlation of the development of the a restrictive disorder and bleomycin administration. Pulmonary ventilation after treatment was examined in a total of 228 patients with the finding of restrictive changes in 94 (41%). Pulmonary fibrosis was diagnosed in 21 patients (9%) with a rising incidence two years after terminated treatment.

[Children of parents treated for Hodgkin's disease using irradiation and chemotherapy]. / Deti rodicu lécených zárením a chemoterapií pro morbus Hodgkin.

The authors describe data on the course of pregnancy, delivery and subsequent development of 20 children born to parents treated for Hodgkin's disease. Thirteen women in the clinical stage II and III were delivered of 16 infants (10 daughters and 6 sons) and three men (II A and III A) had four daughters. The parents were in one case treated by irradiation only, twice by chemotherapy only and thirteen times by a combination of irradiation and chemotherapy (COPP/ABVD). The gestation period, parameters of the infants at delivery and the subsequent physical and mental development are normal. In one instance (a girl, now ten and a half years old) the child was born with malformations of the extremities; according to the geneticist this is not related to the previous treatment of the mother. The second child (a son) of this mother is normal. The authors are of the opinion and apply it in the therapeutic protocol in patients of fertile age and do not irradiate nodes in the pelvic region. In treated patients they allow pregnancy only after three or preferably five years following terminated treatment. Survival of patients in the whole group (269 subjects) regardless of age and clinical stage is 75%. The authors are processing a data base of Hodgkin patients since 1968.

[What is Hodgkin's disease?]. / Co je Hodgkinova choroba?

The article summarizes contemporary views on the aetiology, pathogenesis, therapy and prognosis of Hodgkin's disease. The author emphasizes the necessity of intensive search for the origin of malignant cells. From the therapeutic aspect the necessity of team work and the use of a data base is emphasized which facilitates adaptation of treatment to individual patients, depending on prognostic factors.

[Prognostic factors and their importance in the modification of therapeutic approaches in patients with Hodgkin's disease]. / Prognostické faktory a jejich význam pro modifikaci lécebného postupu u nemocných s Hodgkinovou chorobou.

A prognostic study was performed in a group of 236 long-term followed patients. Eleven factors in total were included into a multivariate analysis--they were global, clinical and therapeutical factors. For complete remission, clinical stage, age at the time of diagnosis and size of affliction of mediastinum are important. Signs of poor prognosis for complete remission are "bulky" mediastinal disease, male sex and absence or reduction of chemotherapy in primary treatment. Prognostic factors as to the total survival are age at the time of diagnosis, clinical stage, total number and size of afflicted lymphatic areas and absence or reduction of chemotherapy in primary treatment. Emphasis is laid upon evaluation of the amount of individual risk to adjust therapeutic procedures to every individual patient.

[Causes of death in patients with Hodgkin's disease]. / Príciny úmrtí nemocných s morbus Hodgkin.

The authors analyze the causes of death of 52 patients from a group comprising 236 patients with Hodgkin's disease. From 51 patients 16 died within one year, with a single exception. All were in clinical stage III-IV (at the time of diagnosis). Within 5 years 40 patients died incl. 4 who the time of diagnosis belonged to clinical stage II. After more than 5 years following establishment of the diagnosis 12 patients died. Of these at the time of the diagnosis 8 were in clinical stage II, 3 in clinical stage III and one patient in clinical stage IV. In the first clinical stage and according to histological classification 10 patients survive, in clinical stage II 93 patients, in clinical stage III 105 patients and 28 patients in clinical stage IV. The mortality rate increases with the advancing clinical stage. Causes of death: progression of the basic disease in 63%, intercurrent infectious diseases in 25%, inhibition of bone marrow in 6%, same percentage for development of secondary neoplasms. The lowest mortality rate was recorded in patients treated by a combination of actino- and chemotherapy (11%), as compared with 23% treated by actinotherapy only and 41% treated by chemotherapy only.

[Relation of HLA antigens to prognosis in Hodgkin's disease]. / Vztah HLA antigenu k prognóze Hodgkinovy choroby.

The prognostic value of HLA antigens in Hodgkin's disease was assessed by multivariate regression analyses. A significantly adverse prognostic impact for achieving complete remission by primary treatment and for its persistence was proved in four antigens locus B (B18, B5, B27 and B15). Five-year survival without signs of the disease, i.e. survival without relapse is significantly lower in subjects with antigen B5, as compared with the group of patients where the antigen was not detected (42% vs. 58%, p = 0.05). An independent prognostic impact of the selected HLA antigens was confirmed in models incl. also formerly tested risk factors for the relapse of Hodgkin's disease.

[BCG immunotherapy in malignant lymphogranuloma]. / BCG imunoterapie u maligniho lymfogranulomu.

The authors investigate within the framework of a multicentre, randomized and stratified investigation the influence of non-specific BCG immunotherapy in adult patients with Hodgkin's disease. The thus created data base was processed according to the Protocol of a prospective study. Supplementary BCG treatment was compared in a group of 112 patients with the fate of 114 patients in a control group without immunotherapy. Although the mean period of complete remission in the group of vaccinated patients regardless of the clinical stage of the disease was 94 months and in the control group 74 months, the difference was not statistically significant. The five-year survival was 93% in vaccinated patients and 91% in the control group. The probability of 10-year survival does not differ substantially in vaccinated patients (88%) and in non-vaccinated patients (85%). There was no difference in the work capacity of patients in the two groups. Immunotherapy was not selected, when testing prognostic factors by Cox' regression analysis, into any of the prognostically favourable models.

[Prognostic significance of mediastinal involvement and post-therapeutic radiographic changes in the intrathoracic area in Hodgkin's disease]. / Prognostický význam postizení mediastina a rtg-polécebné zmeny v nitrohrudní oblasti u Hodgkinovy choroby.

The prognostic importance of mediastinal affection and its extent was analyzed in a group of 220 patients with Hodgkin's disease in all clinical stages. The results of the total survival period in mediastinal patients are significantly worse, as compared with patients without primary affection of the mediastinum at all evaluated time intervals: in the 5th year after onset of treatment 79% vs. 95% in the 10th, 15th and 20th year 67% vs 86%, 63% vs. 86% and 56% vs. 86%. The survival of patients without a mediastinal tumour does not change after a 10-year period of follow-up, in case of a tumour mass up to 1/3 of the transverse chest diameter it declines from 81% in the 5th year to 59 and to 49% in the 10th and 15th year. In case of extensive mediastinal affection only 61% survive 5 years and 42% survive after 10 years. The differences in survival without signs of the disease are not statistically significant, obviously due to primary radiochemotherapy with alternation of cytostatic combinations. There are no significant differences in the frequency of posttherapeutic X-ray changes in the mediastinal area after primary X-ray therapy alone and after chemotherapy alone, as compared with combined radio-chemotherapy with the incidence of postirradiation changes in 30% of the patients: the incidence of post-irradiation changes is potentiated by the administration of bleomycin, depending on the dose. For evaluation of posttherapeutic X-ray changes in the area of the chest it is essential to monitor the patients by X-ray check-ups with concurrent functional examination of the lungs.

[Familial occurrence of Hodgkin's disease]. / Rodinný výskyt Hodgkinovy choroby.

Of a series of 300 patients with histologically verified Hodgkin's lymphoma, six cases of familial occurrence of the disease involving three families were reported from two clinical centers. In two families the affected patients were next of kin (daughter and father in the first family and two brothers in the third one). The interval between the onset of the disease was 6 years in the first and 4 months in the third family. In the second family an aunt and her niece were affected with an 18 year interval in the onset of the disease. The histological type was identical within the families involved (1 x LP and 2 x NS). Deficiency of cellular immunity was established in all the members of the two Prague families and the expression of HLA-A and B antigens of the MHC was determined in the first family. The involvement of environmental and genetic factors in familial Hodgkin's disease was analyzed also in the light of findings reported in the literature.

Study of HLA antigens in patients with Hodgkin's disease.

This paper studies relations of 21 HLA antigens of the A and B loci to selected characteristics in a group of patients with Hodgkin's disease. The investigated characteristics are age, sex, histological patterns, clinical stage and symptomatology. The considered group consists of 68 patients, 37 males and 31 females aged from 19 to 66 years and from 26 to 63 yr, respectively. A comparison between antigen frequencies for patients and controls (301 unrelated blood donors) is carried out. The results confirm that there is no relation between HLA antigens and Hodgkin's disease. A significant increase of A11 is found for females under 40 yr. Certain HLA antigens show significant correlation neither with the patient age nor with clinical or histological stages. A significant increase of B5 is observed for 16 relapsed patients. For them, significant test characteristics are found in the presence of cross-reacting HLA-B5, B35.

A multivariate analysis of prognostic factors in adult Hodgkin's disease.

A multivariate analysis of the prognostic factors was carried out with a Cox model on 167 patients with Stage I-IV Hodgkin's disease. The following indicators were prospectively registered: Sex, age, clinical stage, systemic symptoms, histological type, number of involved areas, nodal size, mediastinal thoracic ratio (MTR), localization of mediastinal involvement according to the aortic arcus, hilar involvement, extent of radiotherapy, and extent and mode of chemotherapy. A linear logistic analysis showed that most of the indicators were interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The three main prognostic indicators for complete remission achievement were age, clinical stage and involvement of lung hili. The three main prognostic indicators for disease-free survival were sex, size of mediastinal involvement (MTR) and use of alternating chemotherapy COPP/ABVD in the initial treatment strategy. The most important prognostic factor for survival was clinical stage followed by hilar involvement, age, and nodal size. The coefficients estimated by Cox regression analysis can be used to combine the important prognostic factors into a single index for each patient at presentation. The prognostic index for each patient would allow the identification of cases with poor prognosis who might benefit from additional initial treatment.

[The effect of radiation on thyroid gland function]. / Vliv záreni na funkci stitné zlázy.

In the submitted review the authors discuss briefly the sequelae of irradiation of the thyroid gland. The most frequent postirradiation affection is usually latent hypothyroidism. The risk of the development of carcinoma in the irradiated gland is cca 200-700 cases per 1 million subjects per year per 1 Gy. The latent period is most frequently 15-30 years. Women and children are roughly twice as sensitive. The authors outline also the problem of 131I and its role in disasters of nuclear reactors. It is considered a 10 times weaker cancerogen than external radiation. In the conclusion the authors discuss possibilities of prevention with a more detailed account of the pharmacological block of the thyroid gland. The authors give also recommended doses to be used in the prophylactic administration of potassium iodide.

Some immunological parameters in Hodgkin's disease.

Mononuclear cells in the peripheral blood of 69 previously untreated patients with Hodgkin's disease were investigated and their changes were followed up in the course of the disease. Before the initiation of the treatment, the total number of lymphocytes, cells with ring-shaped nucleolus, E-rosette forming cells and lymphocytes with dot-like ANAE positivity were decreased and ferritin-bearing lymphocytes significantly highly increased (p less than 0.01) when compared with healthy persons. In cells of the monocyte-macrophage lineage, only the total number of cells in initial state of transformation to macrophages (active nucleolus) was significantly highly increased (p less than 0.05). In comparison with early stages, only the changes of quiet, resting cells were significantly more pronounced in advanced disease (p less than 0.01 and p less than 0.05). An excessive depression of ring-shaped nucleolus-bearing cells was associated with B symptoms. Using a discriminant analysis method, the independent influence of these cells upon the immunocompetence of the patients has been proved. After the completion of primary treatment the changes of cells were more profoundly expressed. No complete restauration of immunocompetence has been found within 1-2 years in patients responding satisfactorily to therapy. Verified by the discriminant analysis, persistent imbalance of T-lymphocyte subpopulations plays the most important role in the immune defect of patients in the second year after the therapy and later.

The clinical contribution of a uniform diagnostic and therapeutic protocol in Hodgkin's disease.

In the period between 5 July, 1968 and 31 December, 1986, a total of 138 patients with Hodgkin's disease were treated at the Institute of Biophysics and Nuclear Medicine of the -- School of General Medicine of Charles University in Prague. In the initial period between 5 July, 1968 and 31 December, 1977 a 10-year survival of 28% and a disease-free survival of 64% were achieved in 29 selected patients. In the next period, the patients were diagnosed and treated according to the uniform protocol used by all centres in the Czech Socialist Republic concentrated in the Lymphoma Cooperative Group. In the whole follow-up period, 5-year and 10-year survival rates of 78% and 75%, respectively, were achieved in 112 surviving persons. The corresponding survival rates in complete remission are 65.5% and 62.5%, respectively. When compared to survival of our patients treated up to 1974, the 5-year survival increased from 40% to 70% in 1986. Improvement of therapeutic outcome is due to more effective treatment. Increased diagnostic accuracy and, thus, also improved disease classification, enables the choice of optimal treatment. The treatment efficacy is documented by restoration of the working capacity in more than a half (51.17%) of patients in our group.