Long-term survival of patients treated for Hodgkin's disease in 1971-1996 depending on the clinical stage of the disease, patient's fertility after therapy and cause of death analysis.

The long-term survival in a group of 370 patients treated for Hodgkin's disease in the years 1971-1996 was retrospectively analyzed. Up to now 191 patients live. 179 patients have died. Since the year 1978 the uniform diagnostic and therapy protocol has been used. The therapy consisted in the combination of a radiation therapy (usual dose 40 Gy) with the COPP chemotherapy (6 cycles). Since the year 1988 the alternation of the ABVD and COPP chemotherapy has been used. According to the stage of the Hodgkin's disease and the patient's age the modification of the therapy was introduced. One chemotherapy cycle was removed for each 10 years above the 50 year age of the patient. The radiation therapy was not applied to the areas of the reproductive organs in young patients to preserve their fertility. The percentage of surviving patients for thirty years was 58.8% for Stage I and IIA,B and for Stage IIIA was 60.72%. In the group of surviving patients, we have registered 11 fathers and 34 females with up to 3 children. All together 75 children without health problems are monitored.

[Results of the monitoring the group of patients treated for the Hodgkin disease in the period of 1971 to 1996. Part 1: long-time survival in dependence of the clinical stage of the disease]. / Výsledky sledování souboru pacientu lécených pro Hodgkinovu nemoc v létech 1971 az 1996. I. cást: Dlouhodobé prezití pacientu v záivislosti na klinickém stádiu onemocnení.

BACKGROUND: This authors team has been dealing with the Hodgkin disease problems since 1971. The MORHO study started at eight working places in 1978 according to unified diagnostic and medical protocol. PATIENTS AND METHODS: 370 patients were treated. The treatment consisted in the combination of radiation and chemotherapy COPP and since 1988 in alternance of COPP and ABVD. Therapy was modificated with accordance to clinical stages and patient's histological type and age. Treatment of the patients over 50 was reduced in decades of one chemotherapy cycle less. RESULTS: Results from the clinical study are--patients with the stage IIA, IIB and IIIA survive 30 years in 59.29%, 57.86% and 60.72%. Patients diagnosed as stage IIIB survive after 30 years 36.78%, while patients in stages IVA and IVB survived 10 years 24.51% and 23.32% and 20 years 8.61% in stage IVB. Women survived longer than men. Histological types had no influence to the lenght of survival. The total number of relapses in the group was 55. There were 39 men and 16 women from that. 64% was in stage III and IV and in 73% mediastinal nodules were affected. 42% of relapses was till 1 year after the treatment. After the treatment 75 children were born to the patients from the group. 60 children from that were born to the women under treatment. CONCLUSION: The success of therapy of Hodgkin's disease according to protocol created by expert group of study MORHO is comparable with results of similar studies in the world. The most important contribution of this study was unification of treatment protocol in Czechoslovakia. This study changed the formerly paliative therapy to real curative treatment.

[Results of the monitoring the group of patients treated for the Hodgkin disease in the period of 1971 to 1996. Part 2: fertility after therapy]. / Výsledky sledování souboru pacientu lécených pro hodgkinovu nemoc v letech 1971-1996. II: fertilita po terapii.

BACKGROUND: This authors team has been dealing with the Hodgkin disease problems since 1971. The MORHO study started at eight working places in 1978 according to unified diagnostic and medical protocol. The aim of this study is evaluation of influence of Hodgkin disease therapy on the fertility in young patients. PATIENTS AND METHODS: Group of patients treated for Hodgkin disease in years 1971-1996 at workplaces using the same treatment protocol has been analyzed and the results have been compared with results of other medical centers in the world. Some of the young patients in fertile age became parents after the treatment. RESULTS: Information of number of pregnancies and of children born, long term surveillance and complications of treatment has been collected and discussed. Many patients stayed fertile also after therapy of numerous relapses. There was 75 children born to 34 women and 11 men previously treated for Hodgkin disease. CONCLUSION: The results of our study are comparable with results of statistial evaluation of similar studies in the world cancer research centers.

[Clinical study of Hodgkin's disease after 25 years]. / Klinická studie MORbus HOdgkin po 25 letech.

BACKGROUND: On the 25th anniversary of the unified protocol of 1978, the authors report the results of the first clinical study in the Czech Republic performed in patients with Hodgkin's lymphoma. 290 patients were treated with both chemotherapy (Cyklophosphamide, Natulan, Prednison, Vinblastin) and radiotherapy according to this widely used protocol. The dosage of cytotoxic therapy was reduced based on age, in patients over 50 years of age. METHODS AND RESULTS: In the year 2003, the survival rate was 77.3% (194/290 patients) and of these, 85% (165/194 patients) have lived more than 10 years with complete remission. Of the 194 surviving patients, 24 were successfully treated for relapses. Of the 66 (22.8%) patients that died, the cause of death in 33 patients was Hodgkin's lymphoma. 33 women of the studied group gave birth to 43 children. In one case, phocomelia was diagnosed post-partum. In this instance, no causal relationship to the cytotoxic treatment (which had been given three years before the birth) could be established. The second child of the same mother was born healthy. In one case, a possible genetic relationship was noted--both the father and the daughter suffered from Hodgkin lymphoma and the granddaughter from non-Hodgkin lymphoma. CONCLUSIONS: The success of this treatment depends on complex diagnostic procedures, and on an experienced team of physicians.

[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.

[Risks of malignant neoplasms in workers in Czechoslovak uranium mines]. / Riziko zhoubného bujení u pracovníku cs. uranových dolu.

The authors present a historical account on the findings which made it possible to define the most serious occupational disease in miners in uranium mines--bronchogenic carcinoma. In 1952-61 44 cases of lung cancer were reported in conjunction with radioactive substances, in 1962-85 already 1511 patients were recompensated. Z. Vích found in a prospective epidemiological survey that of 4803 workers who left for preventive reasons work places involving risk in 1968-75 20.5% died by 1985. The mortality rate from lung tumors was 3.5 times higher than in the male population of the Czech Republic. The authors analyze occupational risk indicators important for the prevention of this occupational disease. From the medical aspect the restriction of mining in uranium mines is welcome, as the work involves a high risk.

[Radioimmunoscintigraphy in experimental and clinical tumors]. / Radioimunoscintigrafie v experimentu a klinice nádorových onemocnení.

Radioimmunoscintigraphy is a diagnostic method which uses labelled monoclonal antibodies for the visualization of tumourous foci. It is a nuclear medical method which is developing rapidly. The author mentions basic investigations on the bio-distribution of antibodies in animal models as well as review of contemporary clinical studies with the diagnostic use of commercial monoclonal antibodies.

[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.

Distribution, kinetics and immunoscintigraphy of 131-I labelled intact antifibrinogen-fibrin antibody (AbFbg) and its F(ab')2 fragment.

131-I-labelled anti fibrin-fibrinogen antibody (AbFbg) was compared with its F(ab')2 fragment in distribution studies and by immunoscintigraphy with a view to tumour visualization in tumour bearing rats. The distribution studies indicated that the intact antibody is more concentrated in tumour tissue than the F(ab')2 fragment. By 168h after injection, when tumour-to-tissue ratios were highest in the majority of tissues, the tumour concentration of intact antibody was 3 to 4 times that of the F(ab')2 fragment. The intact antibody is more suitable than the F(ab')2 fragment for tumour imaging especially in the abdominal region where the highest tumour-to tissue ratios were obtained with intact antibody in liver, spleen, intestines and kidneys.

[Clinical applications of factor analysis in nuclear medicine]. / Klinické aplikace faktorové analýzy v nukleární medicíne.

Factor analysis allows to break up dynamic radionuclide studies into constituent parts corresponding to individual compartments of the distribution space of the radiopharmaceutical in the body. Compartment structure is reflected by factor image and its dynamics is shown by factor time activity curves. The method overcomes the drawbacks of other data processing methods in dynamic scintigraphy by its objectiveness and by distinguishing the projection overlap of tissues with different dynamics. The demands on both the patient and personnel are the same as in standard procedures, yet this method extracts more information from the results of the examination. Higher diagnostic accuracy was reported especially in nuclear cardiology and nephrology. A short survey of clinical applications of factor analysis reported over the years 1982-1988 is presented.

[Immunoscintigraphy in experiments and clinical practice: its possibilities, advantages and limitations]. / Imunoscintigrafie v experimentu, klinice, její moznosti, výhody a omezení.

The authors present their experience gained in preparing, isolating and labeling antibodies with radionuclides for the purpose of using them in immunoscintigraphy. The experimental part includes results obtained with different labeled antibodies and their F/ab/2 fragments in distribution studies, involving also immunoscintigraphic imaging of tumors. The clinical part presents results of immunoscintigraphy obtained with the commercial antibody kits Iodomab and Imacis in patients with tumors of the digestive tract.