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Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease.A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings.0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions.Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

PURPOSE OF THE STUDY Outcome analysis of penetrating cardiac and great vessels injury within the 15-year existence of the cardiac surgery service as a part of the major trauma centre of the University Hospital Olomouc MATERIAL AND METHODS Retrospective analysis of a group of a total of 16 patients who underwent a surgery for penetrating cardiac and great vessels injury since II/2002 to XI/2016. The dominant causes of penetrating trauma were stab injuries (15 patients, 94%), in one patient only (6%) it was a gunshot injury. The mean age of the patients included in the group was 42.9 ± 16.1 years, with men significantly prevailing (13 patients, 81%). A total of 7 injured persons (44%) were haemodynamically stable when admitted, 9 injured persons (56%) were unstable or in critical condition. The average transfer distance was 48.8 ± 34.5 km; the injured were admitted on average 115.9 ± 154.8 minutes after being injured. Preoperatively, all the injured suffered from pericardial effusion (5 mm) confirmed by TTE (81%) or CTA (19%). In 4 patients (25%) pericardial drainage for cardiac tamponade was performed before surgery. RESULTS All the penetrating cardiac and great vessels injuries were repaired by cardiac surgeon, in one case only (6%) the extracorporeal circulation support was used. The injury of coronary arteries was in one case managed by CABG and in the other case by ligation of the peripheral part of the coronary artery. In 4 patients (25%) also a penetrating injury of other organs was simultaneously managed. The mean ICU stay reached 85.8 ± 91.9 hours, on average 5.6 ± 9.3 units of red blood cells were administered during the in-hospital stay which lasted on average 7.1 ± 2.4 days. In the group a nonsignificant increase of left ventricular ejection fraction (44.1 ± 4.7 vs. 49.3 ± 3.2, p = 0.882) was reported at discharge of the injured patients. One patient died on the 78 th day of hypoxic brain damage (6% three-month mortality). The long-term survival analysis showed 94% one-year and 88% five-year cumulative survival in the group. DISCUSSION The incidence of the penetrating cardiac and great vessels injury is directly dependent on the crime level in the respective countries and regions. A cardiac arrest, severe hemodynamic instability, unconsciousness, serious concomitant injury, gunshot injury, multiple or atrial injury represent independent predictors of death in these injuries. The total three-month mortality in penetrating cardiac and great vessels injury ranges from 18 to 42%, the presence of vital signs at the time of hospital admission is associated with 78-92% probability of survival. The surviving patients show excellent long-term results with the exception of those who suffered a severe damage to valve apparatus or with significantly depressed left ventricular function. CONCLUSIONS Our experience proves a high survival rate of patients with penetrating cardiac and great vessels injury. The centralisation of the care into the major trauma centre with a cardiac surgery background, a unified treatment algorithm, and a vital interdisciplinary cooperation are the key goal of successful management of these injuries. Key words:penetrating injury, cardiac injury, great vessel injury, outcome. Práce byla podpořena programem institucionální podpor.

Multiple myeloma is the second most common hematological disease caused by clonal proliferation of B cells. Evaluation of number of plasmocytes in the bone marrow is still one of the basic diagnostic criteria. The aim of this study was to verify if this evaluation has prognostic value even in the era of new drugs.Two groups of MM patients were enrolled in this study. The group T - 45 newly diagnosed MM patients who underwent treatment with thalidomide. Group B - 86 patients in first relapse of MM without autologous transplantation of bone marrow that were treated with thalidomide and bortezomib in various combinations. Percentage of subtypes of plasmocytes in the bone marrow was evaluated based on progressive analysis of nucleus, chromatin and nucleo-cellular ratio (N/C).Mature plasma cells were found in 53.3% (group T) and 53.5% (group B) of patients; proplasmocytes I were found in 22.2% (group T) and 24.4% (group B) of patients; proplasmocytes II were found in 22.2% (group T) and 22.1% (group B) of patients and plasmablasts in 1% (group T) and 0% (group B). Patients who reached treatment response after first treatment had statistically significant number of proplasmocytes II when compared to group without treatment response (median 37% vs. 11%, p = 0.033). Group B patients with mature plasmocytes below 10% had significantly shorter overall survival than other patients when comparison of quartiles was performed. Group B patients with higher infiltration of proplasmocytes I than median of 15% had lower overall survival (median 50.3 months vs. 74.9 months, p = 0,024); the same was true for evaluation of proplasmocytes II (median OS 41.3 months vs. 74.9 months, p = 0,011).Numerical evaluations of plasma cells in the bone marrow remain basic diagnostic criteria of MM even in the era of new genomics analyses. More precise morphological evaluation of 8 subtypes of plasma cells brings important prognostic information that is necessary for new protocols for immunomodulatory drugs and proteasome inhibitors.

Recently, the term biomarker has become, especially in connection with the term clinical proteomics, one of the most frequent terms in the field of biomedical research. The aim of this work was to select an appropriate pre-fractionation method of blood plasma prior to a subsequent proteomic analysis of low-abundant fraction of proteins by two dimensional gel electrophoresis (2-DE) and mass spectrometry to improve the resolution of 2-DE maps and protein identification.First, we compared two prefractionation methods (MARS versus ProteoMiner) preceding 2-DE analysis using 10 blood plasma samples. Based on the results of the comparative experiments, low-abundant plasma protein fractions from 18 multiple myeloma patients treated with bortezomib were analyzed. Patients were divided into two groups: a group resistant to chemotherapy (9 patients--disease progression, stable disease) and a group with positive clinical response (9 patients--complete and partial remission).Samples prefractioned by ProteoMiner method yielded 2-DE maps with a significantly increased number of detected protein spots, as compared to immunodepletion method MARS (Multiple Affinity Removal System). Between groups of chemoresistant and sensitive patients treated with bortezomib, 15 differently intense spots were revealed by image analysis. These spots were found to correspond to 10 proteins, as confirmed by mass spectrometry. Seven proteins had significantly lower protein level in the group of chemosensitive patients (serum amyloid P, fibrinogen--gamma chain, retinol-binding protein 4, complement factor C4-A, apolipoprotein E, carboxypeptidase N and complement factor H-related protein 1) and 3 proteins showed significantly higher levels of protein (or were only detected) in the group of chemosensitive patients (serum paraoxonase 1, alpha-1-antitrypsin and complement factor B).

Multiple angiomatosis is a rare disease causing angiomatous lesions in multiple organs and tissues with a risk of life-threatening haemorrhage.A young man was diagnosed with multiple angiomatosis at the age of 28 after two years of back and abdominal pain. Laparotomy revealed multiple spongy lesions mostly within the retroperitoneal space. Also, an involvement of the gut wall, bones and mediastinum was evident. After 6 years of treatment, the disease has been stabilized. Bone pain ceased with a significant contribution of zoledronate. Using CT and MR imaging, the effectiveness of antiangiogenic drugs was evaluated. Furthermore, treatment response was evaluated using laboratory values for coagulation and blood count, as angiomatous proliferation is known to be associated with disseminated intravascular coagulation and anaemia.Baseline laboratory examination revealed elevated D-dimer (more than 20 µg/mL), low fibrinogen (1.4 g/L), and the presence of fibrin monomers. After treatment with 6 mil. IU of interferon-alpha thrice weekly, there was only partial improvement in D-dimer (17.2 µg/mL) and fibrinogen (1.5 g/L) concentrations but fibrin monomers remained positive. After thalidomide (100 mg daily), D-dimer decreased to 6.1 µg/mL and fibrinogen levels increased to 1.9 g/L with the disappearance of fibrin monomers. CT scanning showed significant regression of angiomatous lesions. Progressive neuropathy was the reason to lower the dose of thalidomide by half and this caused D-dimer to rise again. Switching to lenalidomide 10 mg daily led to an increase in D-dimer to 10.8 µg/mL and decrease in haemoglobin concentration to 124 g/L. Fibrin monomers became positive again. Combined therapy with thalidomide (50 mg/day) and lenalidomide (10 mg days 1-21 in 28-day cycles) has led to stabilisation of the disease. Median concentration of haemoglobin increased to 131 (84-141) g/l. The median of D-dimer decreased to 9.3 (8.0-17) µg/mL.Thalidomide in the dose of 100 mg daily led to better stabilisation of the disease than interferon-alpha. However, lowering the dose because of adverse effects failed to be effective sufficiently. Lenalidomide 10 mg daily was well-tolerated but insufficient to improve D-dimer and haemoglobin concentrations. Therefore, for further treatment we have decided to use the combination of lenalidomide and thalidomide in doses of 10 mg and 50 mg, respectively because both drugs have desirable antiangiogenic activities with different adverse effect profiles. On this therapy, the patients disease has been stable for 9 months.

Erdheim-Chester disease is a very rare syndrome affecting adult population. It typically causes hyperostosis of long bones, retroperitoneal fibrosis and widening of the aortic wall. Patients frequently suffer from disease-associated fevers and pain in the lower limbs. No guidelines are available for the treatment of this rare ailment. Therefore, we describe our experience with lenalidomide in a patient with poor treatment response to 2-chlorodeoxyadenosine.Diabetes insipidus and neurological problems developing over 4 years were the first signs of the disease. The disease was diagnosed from histology of the bone marrow extracted from the ilium. At diagnosis, the patient had multiple infiltrates in the brain, widened wall of the thoracic and abdominal aorta, fibrotic changes to retroperitoneum and typical hyperostosis of the long bones of lower limbs with high accumulation of technetium pyrophosphate as well as fluorodeoxyglucose. First line treatment involved 2-chlorodeoxyadenosine 5 mg/m2 s.c. for 5 consecutive days every 28 days. There was no clear treatment response identifiable on the MR scan of the brain following the third cycle and thus 4th-6th cycle consisted of 2-chlorodexyadenosine 5 mg/m2 + cyclophosphamide 150 mg/m2 + dexamethasone 24 mg day 1-5 every 28 days. After the 6th cycle, MR showed partial regression of the brain lesions. PET-CT showed an increased accumulation of fluorodeoxyglucose in bone lesions. Second line treatment involved lenalidomide 25 mg/day days 1-21 every 28 days. Lenalidomide tolerance was excellent; the number of neutrophils and thrombocytes was within the physiological range throughout the treatment period. Follow-up MR showed complete remission of the brain lesions, while follow-up PET-CT showed further increase in fluorodeoxyglucose accumulation in the bones of lower limbs.Treatment with 2-chlorodeoxyadenosine-based regimen provided partial remission of Erdheim-Chester disease lesions in the brain, while treatment with lenalidomide resulted in complete remission of these lesions. Fluorodeoxyglucose continues to accumulate in the long bones of lower limbs. We are unable to elucidate the reasons for complete remission of the disease in the brain as per the MR and its progression in the long bones according to PET-CT. Further testing of lenalidomide in the treatment of this disease is required to support further use of this perspective treatment option.

Schnitzler syndrome is a rare idiopathic disease characterized by chronic urtica, presence of monoclonal IgM immunoglobuline and further, less common symptoms. This case report describes another case of this disease affecting a male adult born in 1963. The first symptoms, eruptions of non-pruritic urticarial rash, appeared in this patient at the age of 43. In addition, bone pains (mainly tibias) and joint pains (mainly knees) were present. Later on however, severe attacks of fever, chills and shaking together with bone and joint pains were added to during which new urticarial eruptions appeared. Primarily, the man was followed up without any substantial therapeutic results at a department of dermatovenerology, subsequently, due to a finding of monoclonal IgM kappa immunoglobulin (serum concentration 1.9 g/l) he was referred to our department for the reason of gammopathy being a differential diagnosis. On a CT scan hyperostosis in claviculae and pelvic bones was identified. Also on the CT, an increase in cortical thickness was described in the long bones of the lower extremities, where areas of technetium pyrophosphate accumulation were identified on a bone scintigraphy. These areas were found in the chest and sacral regions as well. From the blood exams, the proinflammatory status of the organism was apparent (CRP 35.9 mg/l, erythrocyte sedimentation rate 92 mm/h, leukocytes 12.4 x 10(9)/l). After excluding other differential diagnoses, the patient was diagnosed with Schnitzler syndrome. As regards therapy, we made initial use of the effect of corticoids which abated the symptoms, however, these were causing serious adverse reactions in the form of iatrogenous Cushing's syndrome. The therapy took a turn only after biologic therapy with anakinra (interleukin-1 receptor antagonist) had started, which minimized the Schnitzler symptoms with very good drug tolerance. In the work we measured serum levels of interleukins for disease activity monitoring. The most sensitive were interleukins IL-6 and especially IL-18 the levels of which were the highest at the time of clinical exacerbation of the disease, whereas the levels of IL-1beta and TNF-alpha (tumour necrosis factor) were during all measurements below the limit of detection. Concerning the growing numbers of the reports on successful biological therapy with anakinra and our positive experience, we propose that the therapeutic response to anakinra should be included within the diagnostic criteria of Schnitzler syndrome, which is significant above all in differential diagnosis thereof.

Our paper describes 5 patients with a vascular malformation - angiomatosis. In the first patient, a young man, angiomatosis affected the stomach, intestine, the area of mesenterium and retroperitoneum as well as mediastinum. Angiomatous mass had invaded pelvic bones and vertebrae. Treatment was initiated with interferon alpha in a maximum tolerated dose of 3 million units 3 times a week. Because of low efficacy of interferon alpha, thalidomide was added at a dose of 100 mg per day. Bone pain disappeared following a few applications of zoledronate administered in regular monthly intervals. After 3 years of concomitant administration of interferon alpha and thalidomide, we changed the regimen due to adverse effects and are administering thalidomide and interferon alternatively in 4-monthly intervals. Treatment has resulted in 50% reduction, according to imaging, of angiomatous mass, reduced intensity of disseminated intravascular coagulation and disappearance of clinical signs. The second was a case of multiple angiomatosis affecting the intestine only (multiple intestinal angiodysplasias) where we used thalidomide monotherapy. This treatment reduced blood losses and haemoglobin concentrations rose to normal levels. This male patient had consumed 120 transfusion units per year before the initiation of thalidomide. The third case was a slowly progressing vascular malformation of the face. This vascular malformation troubled its sufferer by spontaneous shortening that could not be resolved surgically because of its fragility. Two years of combined treatment with interferon a 6 million unites 3 times a week and thalidomide 100 mg daily led to a reduction and flattening of the malformation, paling of its colour and ceasing of spontaneous bleeding. This development enabled minor surgery--partial excision of this large vascular malformation. Histology examination confirmed that there was no evidence of new capillary formation. Histological examination thus confirmed efficacy of the treatment. The fourth case involved a patient with large vascular malformations affecting supraclavicular region of the neck and nape in whom radiotherapy was applied (54 Gy) leading to a reduction of the malformation mass by a at least 50%. The fifth is a case of an extensive periorbital lymphangioma that diminished following treatment with interferon alpha. These cases illustrate the benefits of combined treatment including thalidomide and interferon alpha in patients with multiple angiomatosis or large proliferating hemangioma (vascular malformation). If combined treatment with thalidomide and interferon a is not possible, it is beneficial to use thalidomide monotherapy. Radiotherapy is another alternative, although it is necessary to apply doses exceeding 50 Gy which may not be always possible.

Central diabetes insipidus with an onset in adulthood is very rare. Unlike in children, central diabetes insipidus in adults is more frequently caused by inflammatory processes and neoplastic infiltrations that do not originate from the neuronal tissue than primary neuronal tissue tumours. Rare histiocytic neoplasias (Langerhans cell histiocytosis, xanthogranulomatosis and Erdheim-Chester disease) have a specific affinity to hypothalamus and the pituitary stalk not only in paediatric patients but also when occurring in adults. We describe 3 cases of central diabetes insipidus with an onset in adulthood. Diabetes insipidus was the first sign of Langerhans cell histiocytosis in 2 patients, and it was the first sign of Erdheim-Chester disease in one patient. MR imaging showed pathological infiltration and dilated pituitary stalks in all 3 patients. PET-CT proved useful in differential diagnosis, showing further extracranial pathological changes either on the basis of significant glucose accumulation or on the basis of CT imaging. The Langerhans cell histiocytosis in the first patient has also manifested itself as an infiltration of the perianal area with intensive accumulation of fluorodeoxyglucose (FDG) - SUV 8.6 and gingival inflammation indistinguishable from parodontosis. Histology of the perianal infiltrate confirmed Langerhans cell histiocytosis. Infiltration of the pituitary stalk disappeared from the MR image after 4 cycles of 2-chlordeoxyadenosin (5 mg/m2 5 consecutive days). The PET-CT of the 2nd patient showed only borderline accumulation of FDG in the ENT area, while simultaneously performed CT imaging showed cystic restructuring of the pulmonary parenchyma and nodulations consistent with pulmonary Langerhans cell histiocytosis. Bronchoalveolar lavage identified higher number of CD1 and S100 positive elements, consistent, once again, with pulmonary LCH also affecting pituitary stalk and ear canal. The PET-CT of the third patient showed increased activity in the long bones and ilium near the sacroiliac joint. Biopsy of the focus in the ilium confirmed foam histiocyte infiltration immunochemically corresponding to Erdheim-Chester disease. Additional imaging assessments revealed the presence of further signs of the disease. Pituitary infiltrate biopsy in this patient did not elucidate the diagnosis but resulted in complete panhypopituarism. Central diabetes insipidus in adulthood might be the first sign of so far undiagnosed extracranial disease, in our case of histiocytic neoplasias, and PET-CT has an excellent potential to detect extracranial symptoms of these conditions. Therefore, the high-risk pituitary stalk infiltrate biopsy should always be preceded by comprehensive examination aimed at identification of extracranial manifestations of the pituitary gland diseases.

The vacuum-asssited closure has represented an encouraging treatment modality in treatment of surgical site infection in cardiac surgery, providing superior results compared with conventional treatment strategies, particularly in the treatment of deep sternal wound infection.From November 2004 to January 2007, 40 patients, undergoing VAC therapy (VAC system, KCI, Austria, Hartmann-Rico Inc., Czech Republic) for surgical site infection following cardiac surgery, were prospectively evaluated. Four patients (10%) were treated for extensive leg-wound infection, 10 (25%) were treated for superficial sternal wound infection and 26 (65%) for deep sternal wound infection. The median age was 69.9 +/- 9.7 years and the median BMI was 33.2 +/- 5.0 kg/m2. Twenty-three patients (57%) were women and diabetes was present in 22 patients (55%). The VAC was employed after the previous failure of the conventional treatment strategy in 7 patients (18%).Thirty-eight patients (95%) were successfully healed. Two patients (5%) died, both of deep sternal infetion consequences. The overall length of hospitalization was 36.4 +/- 22.6 days. The median number of dressing changes was 4.6 +/- 1.8. The median VAC treatment time until surgical closure was 9.7 +/- 3.9 days. The VAC therapy was solely used as a bridge to the definite wound closure. Four patients (10%) with a chronic fistula were re-admitted with the range of 1 to 12 months after the VAC therapy.The VAC therapy is a safe and reliable option in the treatment of surgical site infection in the field of cardiac surgery. The VAC therapy can be considered as an effective adjunct to convetional treatment modalities for the therapy of extensive and life-threatening wound infection following cardiac surgery, particurlarly in the group of high-risk patients.

The case-report of a 57-year-old patient with the symptoms of massive pulmonary embolism is presented. The patient was admitted to the hospital in the cardiogenic shock, ventilated and with high dose of inotropic support. It was impossible to find out the exact data from personal history. The patient was operated on urgently. The chronic occlusion of the right pulmonary artery due to the chronic tromboembolic disease was found out. Thromboendarterectomy of the pulmonary artery was successfully performed. Three month after operation the patient is in excellent clinical condition almost without any functional limitation. Some atypical features of this case are stressed in the discussion: the urgency of the operation for chronic tromboembolic disease with unilateral involvement, which simulated pulmonary embolism and operation in mild hypothermia without circulatory arrest.

Multiple myeloma is the second most prevalent and mostly fatal hematologic cancer. Further advances have been made in understanding the mechanisms involved in the myeloma pathogenesis and elucidation of critical signalling pathways as therapeutical targets. Proteasome inhibitors are the example of this new approach and bortezomib is the first agent in this class to enter clinical trials.In 6 hematological centers in Czech Republic 29 patients with refractory/relapsed myeloma had been treated with bortezomib (Velcade, Millennium Pharmaceuticals) in 2004. The initial dose 1.3 mg/m2 of Velcade was given, in 1 case the dose was adjusted due to pre-existing renal failure to 1 mg/m2. The response was achieved in 17 patients (59%). Four patients had complete, 11 partial and two minor responses. In 5 cases stabilization of disease was observed and 6 patients progressed during the therapy.Unfortunately, one patient died immediately after the start of therapy due to sepsis. The most common adverse events were thrombocytopenia, anaemia, neuropathy, gastrointestinal complication, renal failure and fatigue. Grade 4 adverse events occurred in 37.9% of patients (4x thrombocytopenia, 2x gastrointestinal, 2x renal failure, 1x sepsis, leucopenia, hepatopathy and anaemia, respectively). Peripheral neuropathic pain of grade 3 was reported in 4 cases, in one patient therapy had to be interrupted due to this complication. We confirmed promising results of phase II trials.

Cytogenetic abnormalities of chromosome 13 are emerging as important prognostic factors in multiple myeloma and have been associated with poor prognosis.The occurrence of 13q14 deletion and other standard laboratory parameters were determined in 40 patients with multiple myeloma. We found that interphase fluorescence in situ hybridization using a locus specific probe for RB1 gene on immunomagnetically selected myeloma cells was more sensitive than non selected cells. The 13q14 deletion was found in 10 of 40 (25.0%) of bone marrow samples without cell selection and in 25 of 40 (62.5%) of samples with CD138+ enriched myeloma cells. Negative correlation was found between albumin and the 13q14 deletion in separated (p = 0.003) as well as in cells without selection (p = 0.010). No significant correlation was found in overall survival of separated and unseparated cells (p = 0.830; p = 0.260) and a similar result was obtained for treatment response after transplantation of separated cells (p = 0.520) or non-separated cells (0.190).Our results confirm that immunomagnetic selection of CD138+ cells increases the probability of detection of the 13q14 deletion in bone marrow samples. The correlation was found between albumin and the 13q14 deletion in both of type of cells.

The objective of the investigation is evaluation of therapeutic results and the development of the prognosis of patients with multiple myeloma (MM) as a result of consecutive changes of therapeutic procedures in patients of central and northern Moravia in the course of the last 40 years.The analyzed group of 562 patients with MM was concentrated at the Ist and IIIrd Medical Clinic of the Faculty Hospital Olomouc in 1959 - 2000, median age 63 (28-91) male/female ratio 1.1: 1.0. From analysis of Kaplan-Meier survival curves and the results of statistical analysis (log rank test p = 0.0000) ensued that during the evaulated period a very substantial change of prognosis occurred with improvement of theraupeutic results and a significant prolongation of survival in general. The first " turning point" was the introduction of chemotheraphy with alkylating substances with Prednisone (1963-1975), leading as compared with the period of symptomatic treatment alone (1959-1063) to a significant prolongation of the media value of general survival (M) from 8 to 19 months (p = 0.0031) and 3-year survival from 4 to 23 % patients, whereby 10-year survival was only 0 % and 1 %. The second "turning point" was the period from 1976 - 1980 with introduction of systematic chemotherapy using conventional doses of polychemotherapeutic (CP) regimes with better opportunities of supporting treatment (M = 40 months, p = 0.0000; 3-year and 10-year survival 55% and 5.5% patients). The therapeutic results acheived during the subsequent 15 years were however an unsatisfactory advance. During the interval between 1976-1995 in a group of 295 patients divided into 5-year sub-periods remission was acheived (R =25 % of the baseline value of M-protein) in 10-24 % patients, an inadequate response (NR) = persistence in50 % M-protein) in 55-28 %, prolongation of the median of total survival in 232 of the accessble patients for 44 months and long-term survival of 5 - 10 years after establisment of the diagnosis increased from 25 to 36 % and from 5.5 to 16.5 % patients. The third "turning point" was 1996 characterized by the introduction of high-dosage chemotheraphy with transplantation of autologuos peripheral haematopoietic cells ("HD" therapy with ASCT) leading ina group of so far only 33, assessable patients under 65 years to acheived remission in 71 %, to decline of NR in 10 % only and 5 -year suvival so far in 91 % patients ( p = 0.0037). Improvement of therapeutic results and prognosis of the disease as compared with 1976 - 1995 occurred in the whole group of patients also in 1996 - 2000 (CP and "HD"-therapy with ASCT) characterized by remission in 36 %, NR IN 33 % and 5 -year survival in 57 % (p = 0.030). It was reveled that the application of "HD" theraphy with ASCT led in 1995-2000 to the acheivement of more favorable therapeutic results (R - 71 % NR - 10 %. 5-year survival after the interval which elapsed so far 91 %), as compared with 2 similar groups of subjects under 65 years meeting the criteria of "HD" theraphy with ASCT, but treated only by conventional polychemotheraphy (1991 - 1995 and 1996 - 2000: R - 24 and 32 %, NR - 42 and 23 %, 5-year survival 46 and 68 % of the patients). In the group of 148 patients from the period of 1991-2000 the patients had as regards remission (R) more favourable results as compared with patients with NR concerning the prognosis [M 63 vs.22 months, 5-year and 10-year survival 53 vs. 17 % and 17 vs. 0 % of patients (p = 0.0000)].From the submitted analysis ensured that during the period form 1959 - 2000 in patients with mutiple myeloma in central and northern Moravia as a result of the application of modern methods of chemotheraphy and supporting treatment a significant improvements of results of conventional treatment occurred with a more than 5 fold prolongation of so far assessable median values of survival (8 - 44 months) and long-term 10-year survival of almost one sixth of the patients. The real asset of "HD" theraphy with transplantation of ASCT will be revealed by analyses made after a longer time interval.

Autologous peripheral blood stem cell transplantation (APBSCT) is gradually replacing autologous bone marrow transplantation in many clinical settings. The key question is how to evaluate the quality of grafts. We analyzed the relationship between hematopoietic reconstitution and characteristics of patients and grafts.Data from 95 APBSCTs were analyzed. Peripheral stem cells were obtained after mobilization using anti-neoplastic chemotherapy followed by Neupogen (G-CSF). After high dose chemotherapy and APBSCT, patients received Leucomax (GM-CSF). Patients were reinfused with a median of 6.1 x 10(6) (range 0.83-29.3) CD34+ cells/kg, and 25.1 x 10(4) (range 1.0-167.0) CFU-GM/kg of body weight. The median time to engraftment was 12 days (both for granulocytes 1 x 10(9)/l and platelets 50 x 10(9)/l). We found a significant correlation between the number of CD34+ cells and CFU-GM reinfused and also between their respective graft sizes and time to leukocytes, platelets, and granulocytes recovery. We did not find a significant correlation between the number of mononuclear cells reinfused and any analyzed parameter (time to engraftment, age, diagnosis, number of previous chemotherapies, type of mobilization or high-dose regimen). However, administration of preparative high-dose chemotherapy consisted of busulphan and cyclophosphamide was associated with the risk of a transient secondary graft failure.We conclude that the content of progenitors in PBSC grafts and time to booth leukocyte and platelet recovery are best estimated by the number of CD34+ cells (not less than 1 x 10(6)/kg) and CFU-GM (not less than 1 x 10(4)/kg). The number of mononuclear cells in an autologous PBSC graft is not suitable and useful for prediction of engraftment rate. There is probably no additional benefit of reinfusion of more than 8-10 x 10(6) CD34+ cells/kg and/or 50 x 10(4) CFU-GM/kg, because hematopoietic recovery is not more rapid.

In patients with haematological malignities infectious complications take a very rapid course, and in particular during the period of neutropenia, they are not necessarily manifested by a clear symptomatology. Frequently they may be manifested only by an elevated temperature and general deterioration of the condition. The onset of shock then can be rapid and surprising. The objective of the work was to identify clinical and laboratory signs warning against the possible development of septic shock.The investigation comprised a total of 38 patients hospitalised due to infectious complications at the intensive care unit because of general deterioration of the condition. 18 developed septic shock (group S), the remaining 20 (group N) achieved during hospitalisation at the ICU a stabilised condition. In both groups the laboratory values and clinical condition were followed up for 2-3 days prior to deterioration of the condition. Risk factors for development of septic shock in the group of investigated patients were: unusual weakness, heart rate above 95/min. beyond the temperature peak, hypoalbuminaemia, mucositis, hypokalaemia, presence of a central venous catheter and administration of parenteral nutrition.

Treatment of Hodgkin's disease (HD) and non-Hodgkin lymphomas (NHL) is still unsatisfactory in patients resistant to primary therapy or those with early relapses. The objective of the trial was to test whether salvage regimens based on a combination of iphosphamide and etopozide have a sufficient anti-lymphoma effect, while the toxicity is still acceptable, and in conjunction with growth factors as satisfactory mobilizing potential for the collection of peripheral stem cells (PBSC).A group of 40 patients with relapsing and/or primary therapy resisting lymphomas (14 NHL, 26 HD) were treated by life saving or stimulating chemotherapy VIM (etopozide, iphosphamide, methotrexate) and MINE (iphosphamide mitoxanthrone, etopozide; mostly NHL). If the response to these regimes was inadequate, to some patients in addition mini (dexa) regimes were administered, BEAM and DHAP resp., with the objective to achieve maximum reduction of the tumourous mass before high-dosage treatment with the support of autologous PBSC. The authors administered 119 cycles of salvage chemotherapy (51 VIM, 46 MINE, 22 mini-dexa-BEAM and DHAP). The toxicity of chemotherapy and the therapeutic response were evaluated according to WHO criteria. The toxicity of VIM and MINE, with the exception for mobilization of desirable transient leukopenia, was not serious. During stimulation of PBSC on average three leukophereses were made and on average 9.9. 10(6) CD34+ cells/kg body weight of the patient were obtained and 53.2. 10(4) CFU-GM/kg (VIM), and 13.5. 10(6) CD34+ cells/kg 53.4. 10(4) CFU-GM/kg (MINE) resp. A total of 64% (MINE) and 61% (VIM) therapeutic responses were obtained, 14% (MINE) and 26% (VIM) complete remissions and 50% (MINE) and 35% (VIM) partial remissions.Life saving regimes, VIM and MINE, have a good antilymphoma activity, low toxicity and in combination with growth factors (filgrastim) they ensure a good collection of PBSC. As compared with other regimens, in particular for stimulation, VIM and MINE appear to be better.

The cardiotoxicity of anthracycline antibiotics is a serious complication of anti-tumourous treatment. One of the possible ways how to prevent it or at least restrict it substantially is to use cardioprotective substances. The latter include ICRF-187 bispiperazinedione (dexrazoxan) which is manufactured and supplied by CHIRON Cop. under the name Cardioxane. The authors investigated by echocardiography indicators of systolic and diastolic function of the left ventricle in patients where cumulative doses of 180-240 mg/sq.m of doxorubicin were achieved. In 10 patients to whom Cardioxane was administered no changes of left ventricular function were recorded. In 18 patients treated with boluses of doxorubicin significant deterioration of left ventricular diastolic function developed. The authors provided evidence that relatively small cumulative doses of doxorubicin administered as boluses lead to impaired left ventricular diastolic function. These changes were not recorded in patients who were given the cardioprotective substance ICRF-187 (Cardioxane).

Multiple myeloma is very frequently associated with anaemia which has the character of hypo-proliferative anaemia of chronic diseases. In this type of anaemia the erythropoietin formation is frequently inadequate. According to data in the literature pharmacological doses of erythropoietin lead to an increase of the haemoglobin concentration in blood. Erythropoietin (Eprex Cilag) was administered to 11 patients whose haemoglobin concentration was lower than 100 g/l. The results from 10 patients were finally evaluated. During the first month all patients were given erythropoietin - 150 U/kg three times per week. Unless during the first month of treatment the haemoglobin concentration increased by 10 g/l, the dose was doubled to 300 U/kg. In patients where the haemoglobin value had risen above 120 g/l, the authors assessed an individual maintenance dose. In case three-month erythropoietin treatment did not lead to an increase of haemoglobin by 20 g/l as compared with the baseline value, erythropoietin administration was discontinued. The haemoglobin concentration increased by 20 g/l in a total of 8 (80%) of 10 evaluated patients. In all five patients where the haemoglobin concentration increased by 20 g/l during the first month, the endogenous erythropoietin concentration was less than 60 U/l. In another three patients the mentioned therapeutic response was recorded only during the 2nd or 3rd month of treatment after the erythropoietin dose had been increased. These three patients had higher baseline concentrations of endogenous erythropoietin, 100 to 350 U/l. During treatment no undesirable effects of erythropoietin were observed. Erythropoietin is a useful drug for anaemic patients with the diagnosis of multiple myeloma. According to the results of the authors work and data in the literature it is obvious that in patients with endogenous serum erythropoietin below 100 U/l a rapid riae of haemoglobin can be observed already during the first month. Patients with a higher baseline concentration of endogenous erythropoietin (100 to 500 U/l) respond less frequently to treatment and larger doses of erythropoietin must be administered. In patients with an erythropoietin value above 500 U/l there is a minimal probability that a response will be produced.

Multiple myeloma is very frequently associated with anemia which has the character of hypoproliferative anemia of chronic diseases. In this type of anemia there is often insufficient production of endogenous erythropoietin. According to literature pharmacological doses of erythropoietin result in the increase of blood hemoglobin concentration. Erythropoietin (Eprex Cilag) was given to 11 patients whose hemoglobin concentration in blood was lower than 100 g/l. 10 patients could be evaluated at the end of the study. Within the first month all patients were given erythropoietin in the dose of 150 U/kg 3 times a week. The dose was doubled, when the blood hemoglobin concentration did not increase by more than 10 g/l within the first month. In patients with hemoglobin level above 120 g/l we were trying to find the individual maintenance dose. In patients who had not reached a blood hemoglobin concentration increase of at least 20 g/l, as compared with the initial level, further erythropoietin administration was stopped. The concentration of hemoglobin increased of 20 g/l in 8 (80%) out of 10 patients evaluated. All 5 patients who responded within the first month, had had pretreatment concentration of endogenous erythropoietin below 60 U/l. Three other patients had not been responding before their dose of erythropoietin was increased in the 2nd and 3rd months of therapy. The therapy response appeared only in the 2nd and the 3rd months of treatment. These 3 patients had higher pretreatment concentrations of endogenous erythropoietin, from 100 to 350 U/l. During the treatment no adverse effects of erythropoietin were observed. Erythropoietin is a useful drug for anemic patients with the diagnosis of multiple myeloma. According to the results mentioned above and also according to the data from literature it is evident that in patients with the endogenous blood erythropoietin value below 100 U/l it is possible to expect a sudden rise in hemoglobin concentration already within the first month. Patients with a higher concentration of endogenous erythropoietin (100 to 500 U/l) respond to the therapy less frequently and for the increase in hemoglobin it is necessary to give higher doses of erythropoietin. Patients with the initial value of erythropoietin above 500 U/l are not likely to respond.

Maintenance of satisfactory and safe venous access in cancer patients is part of a comprehensive care of cancer patients. As the Hickman/Broviac catheter is today used an implantable port. This port is placed in a subcutaneous pocket. The catheter connected to the port leads into the central vein, usually through the subclavian vein. An application of drugs in the port is done trough the skin. In this time could be used different types of ports, one or two chambers port, low profil port, peripheral port and others. In this paper we reported our two-years experience with 33 totally implantable access systems, which has been implanted in patients with cancer in Masaryk University Hospital Brno Bohunice. In our department was most frequently used port the nonmetallic port IMPLANTOFIX (BRAUN MELSUNGEN). All ports were in place for a total of 5,582 days, in average of 169 days. A frequency of complications were 2.15 on 1,000 days. Four ports were in place for longer than 1 year. A comparison of the incidence of complications in the present study with an analysis of 23 studies reported in literature was satisfactory. Minimal maintenance care, no restriction of life activity, improving quality of life and probably less frequency of infection complications, identify it as a significant advantage for the satisfactory maintenance of venous access of oncology patients in comparison with Hickman/Broviac catheter. Both the patients and the nursing staff showed a very high degree of satisfaction with this system. In cancer patients, especially with poor venous access, and prognosis longer than 6 months can be indicated this system with the advantage for patients.

The therapy of primary amyloidosis is still unsatisfactory. The response rate after the cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinaemia, brought us to the idea to test interferon alpha in the therapy of primary amyloidosis. Interferon alpha-2b was administered to the patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) daily for the treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

Standard treatment of refractory myeloma is combined VAD treatment (vincristine, adriamycin and dexamethasone). In recent years adriamycin was sometimes replaced by mitoxanthrone which caused greater myelotoxicity. As a positive feature of the exchange of adriamycin for mitoxanthrone, authors using it, report its lower cardiotoxicity. In the literature there are, however, occasional reports on a lower cardiotoxicity of adriamycin when administered in a continuous infusion. In the submitted work the authors sought answers to two questions. 1. Is the cardiotoxicity of adriamycin administered in a continuous infusion lower than the cardiotoxicity of adriamycin administered as a bolus? 2. Is it possible to add to VAD chemotherapy cyclophosphamide without increasing the toxicity excessively? After echocardiographic evaluation of the diastolic and systolic function following a cumulative dose of 200 mg the authors observed smaller changes of the above functions in the group treated with adriamycin a in a continuous infusion (patients with multiple myeloma) than in the group with bolus therapy (patients with non-Hodgkin lymphomas and acute leukaemia). Addition of 600 mg cyclophosphamide on the 5th, 10th and 20th day to the classical VAD pattern made treatment more intensive without causing a deteriorated tolerance of this treatment.

The therapy of primary amyloidosis is still unsatisfactory. The response rate after cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in the majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinemia, brought us to the idea to test interferon alfa in the therapy of primary amyloidosis. Interferon alpha-2b was administered to a patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) i. V. daily for a treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study.

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.