Hereditary haemorrhagic telangiectasy is an inborn disease with autosomal dominant transmission. Nose bleeding usually occurs during the 2nd decade of life as the first sign of the disease. Later, during the 3rd or 4th decade of life, typical subtle, pinhead-sized (1-2 mm in diameter) vascular arteriovenous malformations occur. These are usually found on the oral mucosa and in the stomach and small intestine. During later stages of the disease, nose as well as gastrointestinal bleeding causes severe anaemia requiring transfusions. Advanced stages of hereditary hemorrhagic telangiectasy are associated with a development of ateriovenous vascular malformations in the liver, lungs and possibly the brain. Vascular ateriovenous malformations in the liver cause hyperkinetic circulation that may lead to heart failure. Blood within the pulmonary ateriovenous malformations bypasses filtration in the pulmonary capillary circulation and thus infected microtrombi may pass from the inferior vena cava to, for example, the brain. At first, local treatment - stopping epistaxis - is used. Symptomatic embolisation treatment and, sometimes, liver transplantation are used in advanced forms of the disease with anaemisation, despite iron substitution, and clinically significant ateriovenous malformations. Angiogenesis-inhibiting substances have been shown effective in patients with an advanced disease. Older clinical studies confirmed benefits of combined oestrogen-progesterone treatment, later also treatment with raloxifene or antioestrogens. Many post-2000 publications showed thalidomide and bevacizumab to be effective in this indication. Treatment with bevacizumab has led not only to increased haemoglobin concentrations but, through regression of ateriovenous malformations, provided control of hyperkinetic circulation. Discussion section provides an overview of treatment modalities. The main text describes a case of a 56 years old female patient with hypochromic anaemia despite maximum oral iron substitution. The patient lost blood through repeated epistaxes as well as continuous mild bleeding into gastrointestinal tract. The patient also had confirmed large ateriovenous malformations in the liver. Interferon alpha was used as the first line of treatment. The patient unexpectedly developed fast and pronounced myelosuppression. The number of neutrophils fell down from 1.15 x 109/l to 0.6 × 109/l as soon as after 3 injections of interferon alpha at a starting dose of 1.5 million units 3 times a week. Therefore, interferon alpha was discontinued. Blood count returned to normal following interferon discontinuation. The patient was started on thalidomide in December 2011. The patient reported lower incidence of epistaxes and smaller blood loss than before treatment as soon as during the first month of therapy. Regular administration of thalidomide reduced intensity and frequency of epistaxes in this patient.
IgA pemphigus, resembling subcorneal pustulous dermatosis, represents a rare complication of IgA type monoclonal gammopathy. The patient dates the onset of initial symptoms of vesicular-bullous disease to 1990. She was first examined at our clinic in 2001 with the following conclusion "type IgA monoclonal gammopathy of unknown significance". The first immunosuppressive treatment of vesicular-bullous disorder was administered in 2003 (dexamethasone 20 mg on days 1-4 and 15-18 in monthly cycles + daily cyclophosphamide 50 mg). Cyclophosphamide was administered for 6 months in total and dexamethasone for further 3 months. During the treatment, intensity of the skin disorder ameliorated and monoclonal IgA levels decreased to non-detectable levels. Nevertheless, skin symptoms recurred immediately after dexamethasone treatment in its original intensity was terminated, even though the concentration of monoclonal immunoglobulin IgA remained below the sensitivity of quantitative detection for further 6 months (positive immunofixation only). Six rituximab 600 mg infusions were administered in a weekly interval after stopping cyclophosphamide and dexamethasone to prevent early recurrence of skin symptoms but this treatment was without any lasting effect. Transformation into multiple myeloma was identified in 2007. First line treatment (cyclophosphamide, adriamycin and dexamethasone - CAD) remained without any haematological or dermatological treatment response. Second line treatment (thalidomide, cyclophosphamide and dexamethasone - CTD) brought about significant deterioration of skin symptoms up to the clinical picture of erythrodermia. Third line treatment (bortezomib 1.3 mg/sqm i.v. on days 1,4, 8 and 15, cyclophosphamide 50 mg daily and dexamethasone 20 mg on days 1-4 and 15-18 in 28-day cycles - VCD) resulted in rapid decline in monoclonal immunoglobulin IgA concentrations immediately following the first cycle and to negative immunofixation after 5 cycles. In total, six VCD cycles were administered. The patient has had no skin symptoms from the third cycle of this treatment and complete skin and haematological remission has been maintained for 12 months after completion of bortezomib-containing treatment. Combined treatment containing bortezomib has proven useful in the treatment of IgA pemphigus accompanying monoclonal gammopathy of uncertain significance transformed into multiple myeloma.
- MeSH
- bortezomib MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dexamethason aplikace a dávkování MeSH
- imunoglobulin A krev MeSH
- kyseliny boronové aplikace a dávkování MeSH
- lidé MeSH
- mnohočetný myelom komplikace farmakoterapie MeSH
- paraproteinemie komplikace MeSH
- pemfigus komplikace imunologie patologie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- pyraziny aplikace a dávkování MeSH
- senioři MeSH
- vezikulobulózní nemoci kůže komplikace diagnóza MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Názvy látek
- bortezomib MeSH
- cyklofosfamid MeSH
- dexamethason MeSH
- imunoglobulin A MeSH
- kyseliny boronové MeSH
- pyraziny MeSH
B-cell chronic lymphocytic leukaemia and the similar diseases are seen predominantly in patients above the age 50 years, i.e. at the age when the patients also have other co-morbidities. The knowledge of these diseases on molecular level has improved significantly over the last decade. Molecular and biological prognostic factors are available in routine everyday practice. Assessment of these factors enables prediction of prognosis and, in some cases, also the response to therapy. The aim of the present review is to provide the medical community with the main information on this disease as patients with B-cell chronic lymphocytic leukaemia and similar disease states are of older age and very often suffer from a range of co-morbidities. Consequently, care for these patients involves physicians from various specialities. The aim of the following text is to present a clear overview of the basic information about this group of diseases that might be useful to all physicians who provide care to patients with B-cell chronic lymphocytic leukaemia and similar conditions. Since monoclonal immunoglobulin is sometimes identified in patients with these diseases, it is important to consider these conditions in the differential diagnosis of the states with the presence of monoclonal immunoglobulin.
- MeSH
- chronická lymfatická leukemie diagnóza MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- mnohočetný myelom diagnóza MeSH
- paraproteinemie diagnóza MeSH
- prolymfocytární leukemie diagnóza MeSH
- vlasatobuněčná leukemie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
Autologous and allogeneic transplantations of haematopoietic cells form an important part of treatment of, particularly haematological, malignancies but have their place in the treatment of other diseases as well. Transplantation brings permanent remission in a number of patients. However, transplantation, and the allogeneic one in particular, is associated with a range of complications. The following review paper provides information on the types of transplants, their collection and processing, on the options for and ways to seek suitable donors of haematopoietic cells. Other sections of the paper focus on preparatory pre-transplantation regimens and complications that might occur after the transplantation. Finally, the paper reviews clinical uses of haematopoietic cell transplantations and provides a summary of diagnoses in which this treatment method can be applied.
Several randomized clinical trials in multiple myeloma (MM) completed in the last two decades have clearly shown that high-dose chemotherapy with hematopoietic stem cell support significantly increases the number of complete remissions and median overall survival in comparison to conventional chemotherapy. The median survival of MM patients treated with conventional chemotherapy is approximately 4 years in contrast to 5 to 6 years with autologous transplantation. Although high-dose chemotherapy with autologous transplantation is not curative and most patients will eventually relapse, more than 20% of patients treated using this strategy experience survival longer than 10 years. Thus, autologous transplantation is the preferred treatment option for all eligible patients with MM.
- MeSH
- antitumorózní látky aplikace a dávkování MeSH
- autologní transplantace MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- mnohočetný myelom terapie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antitumorózní látky MeSH
Waldenström macroglobulinaemia (WM) is a disease the incidence of which is approximately 10 times lower than that of multiple myeloma. The incidence of WM is reported to be respectively 0.34 per 100,000 men and 0.7 per 100,000 women. It is one of the less aggressive lymphoproliferative diseases in which therapy is indicated only when the disease symptoms start to manifest. We present a retrospective analysis of patients with the symptomatic form of WM who were treated with chemotherapy in our centre over the last 9 years, i.e. 19 WM patients (of which 7 women and 12 men). The median age upon diagnosis of the symptomatic form of WM and start of treatment was 59 (51-78) years. The median follow up for all patients was 31 (7-121) months. The most frequent indication for WM treatment was anaemia in 57% (11/19), thrombocytopaenia in 21% (4/19), plasma hyperviscosity in 42% (8/19), symptomatic lymphadenopathy in 15% (3/19), and pathologic osteolysis in 15% (3/19) ofcases, respectively. Decrease in immunoglobulin concentration under the lower physiological limit is not referred to as a characteristic sign of WM, yet it was recorded in 7 out of 19 patients in our patient group and continued after chemotherapy, with the affected patients suffering from infections in remission more often than those with physiological values of immunoglobulins. 36% (7/19) patients were treated with R-FC (rituximab + fludarabine + cyclophosphamide) therapy, 15% (3/19) with FC therapy, 15% (3/19) with R-CHOP concluded by high-dose chemotherapy with autologous transplantation in 1 case, and 5% (1/19) with CHOP therapy. VAD (vancristine, ariamycine and dexamethasone) therapy was used in 10% (2/19) of patients and 10% (2/19) of patients were treated with oral chlorambucil. The first line of treatment achieved complete remission (CR) in 15% cases (3/15). Two patients who achieved CR were treated with R-FC, and one patient with VAD. Partial remission (PR) was achieved by 63% of patients (12/19). Minor response (MR) was achieved by 10% (2/19), and stable disease (SD) was recorded in 10% of patients (2/19) after initial treatment. The first relaps of the disease was recorded in 5 patients (2 of whom had PR and 3 MR) who achieved remission after additional lines of therapy. Thirteen patients are in the first PR. With a follow up median of 31 months (7-121), only 2 patients died from other than the underlying disease. Additional malignant disease was diagnosed in 3 patients: 1 colon carcinoma, 1 acute myeloid leukaemia (AML) and 1 myelodysplastic syndrome (MDS). All three received fludarabine and cyclophopsphamide as initial therapy. Of the three patients only the patient with MDS has survived and is now without any evidence of the presence of WM, i.e. in complete remission at 41 months after the start of therapy. High-dose chemotherapy with autologous transplantation was used in 2 cases, once as part of initial therapy and once as part of the therapy for the first relaps resistant to R-CHOP chemotherapy. It is not possible to determine the median of the first remission or the median of total survival due to the short follow up interval.
Over a period of 18 years, 17 patients with proven Langerhans cell histiocytosis (LCH) were treated at the Haematological Clinic in Brno. In 13 of them, the disease was diagnosed at adult age, and 4 patients were referred to the centre with LCH diagnosed at early child age. One of these 4 patients suffered from repeated recurrences of the disease at adult age and was diagnosed with progressive neurodegenerative damage of the CNS at the age of 25 which in its terminal phase resulted in the patient's immobility, loss of sphincter control, incapacity to communicate and death at the age of 32. LCH was diagnosed at adult age in 13 patients. The form with primary bone involvement was detected in 8 out of 13 patients (62%). Only 2 of 13 patients (15%) had multiple bone lesions upon diagnosis, the remaining 6 patients (46%) had only one lesion at the time of diagnosis. Repeated recurrence of bone involvement was only recorded in 3 out of 13 patients (23%). The combination of recurrent bone involvement and the development of lung affection (dyspnoea, irritating cough, nodularities and cysts in HRCT images) were documented in 2 out of 13 patients (15%). One of the patients diagnosed with LCH at the age of37 had repeated recurrence of bone involvement, which was also treated by 2 cycles of high-dose chemotherapy and autologous transplantation. He died of bronchopneumonia due to the affection of the lungs by LCH at 48 years of age. Primary extraoseal (extamedular) involvement was diagnosed in 5 out of 13 patients (38%) (mandibular gum infiltration, single cervical node infiltration, hand skin infiltration, infiltration of the perineal region and infiltration of the hypophysial infundibular and primary lung form of LCH). In the 1st case, excision was the solution applied to the infiltration of the lingual side ofthe gums, without further recurrence. In the 2nd case, the infiltrated region of skin over the metacarpophalangeal joint was irradiated and the infiltration disappeared. In the 3rd case, the first sign ofthe disease was diabetes insipidus in a 34-year-old man, and an infiltrate in the anal region similar to condylomata acuminata. The diagnosis was confirmed 2 years after the development of diabetes insipidus from perianal infiltrates. After treatment with leustatin in 4 cycles (10 mg a day for 5 consecutive days), control MR showed that the infiltration in the hypophysial infundibular had disappeared, while the finding in the perianal region only regressed by 50% after therapy with leustatin, the reason for subsequent application of radiotherapy (20 Gy). The finding in the perianal region is normal one year after therapy, but substitution therapy with adiuretin is still necessary. The 4th patient was a case of LCH with primary pulmonary involvement diagnosed on the basis of HRCT and lavage with an immunohistochemical proof (expression of CD1 and of protein S-100) of a high number of Langerhans cells. The occurrence of LCH at adult age is rare and the disease may affect the skeleton as well as other organs. Therefore each new osteolytic lesion should be submitted for histological exam, as well as each pathologic formation, because diagnosing the disease without a microscopic and immunohistochemical exams is not possible. In the case of occurrence of diabetes insipidus at adult age, LCH should be considered as one of the possible underlying diseases. LCH pulmonary involvement should be considered in patients with an interstitial pulmonary process and the examinations should be focused accordingly (thoracoscopy with sampling for histological exams or bronchoalveolar lavage) plus the indispensable immunohistochemical examination.
- MeSH
- dítě MeSH
- dospělí MeSH
- histiocytóza z Langerhansových buněk * diagnóza patologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
UNLABELLED: The aim of this study was investigate the appearance of multiple myeloma on flurorine--18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient's management were evaluated. METHODS: Altogether 50 patients, 13 patients with newly diagnosed multiple myeloma with negative radiographs, 4 patients with solitary plasmocytoma, 27 patients in remission with suspected relapse and 6 patients with monoclonal gammopathy of unknown significance (MGUS) with suspicion for multiple myeloma or other malignancy underwent FDG-PET examination. The results of routinely performed radiographs, and MR or CT imaging modalities as well as the clinical course were used for verification of the FDG-PET results. RESULTS: Focally increased tracer uptake was observed in 3 (23 %) of newly diagnosed myeloma patients with negative radiographs and was verified with CT or MR with followed indication for therapy. The FDG-PET was negative in two cases of newly diagnosed multiple myeloma with negative radiographs, no focal infiltration on MR imagination, but with anemia, high monoclonal imunoglobulin and bone marrow infiltration, which was indication for therapy. In all other cases FDG-PET negativity in asymptomatic myeloma had good prognostic significance; these patients are without progression after with a median follow up 14 (7-20) months. Focally increased tracer uptake was found in 5 of the 27 patients in remission. In 4 cases of them it was due to multiple myeloma relapse, in one case due to ovarial carcinoma. Only in 1 patient the PET-FDP failed to recognize extraosseal progression on the scull. 21 patients had true negative FDG-PET imagination, in 1 case disease relapsed 12 months after FDG-PET examination; the other 20 patients are still without progress of this disease with median follow up 15 (7-20) months. FDG-PET was positive in 2 from the 6 patients with MGUS. In one of them carcinoma of thyreoidea was detected, in second the FDG-PET activity was localized in gut, tumor was verified with CT and colonoscopy. CONCLUSION: In conclusion, FDG PET might contribute to initial staging of radiographs negative multiple myeloma and might be useful for follow up of patients in remission, especially in consecratory multiple myeloma, or in patients with large plasmocelular tumor (> 5 cm) after concomitant radiochemotherapy.
- MeSH
- dospělí MeSH
- fluorodeoxyglukosa F18 * MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom diagnostické zobrazování MeSH
- paraproteinemie diagnostické zobrazování MeSH
- pozitronová emisní tomografie * MeSH
- radiofarmaka * MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fluorodeoxyglukosa F18 * MeSH
- radiofarmaka * MeSH
Antiphospholipid antibodies (APLA) present very heterogeneous groups of antibodies which can significantly and in various ways influence processes on different levels of coagulation cascade. Their presence can be accompanied with repetitive venous and arterial thromboses, recurrent loses of foetus, and thrombocytopenia. Incidence of these thrombotic disorders was monitored in a group of 46 patients with systemic lupus erythematodes (SLE). Positive lupus anticoagulant (LA), antiphospholipid antibodies complex, and thrombocyte counts were assessed. Thrombotic disorders were assessed in a retrospective analysis. In the LA+ group 62% of patients had history of venous thromboses, 31% had history of arterial thromboses, and 18% had history of spontaneous abortions. In a group without positive LA 18% of venous thromboses (p = 0.0006) and 6% of arterial thromboses (p = 0.03) were indicated. In the assessment of spontaneous abortions no statistically significant difference was found. An average value of thrombocytes in LA+ group was 152 +/- 66 x 10(5)/l, in LA- group 223 +/- 86 x 10(5)/l, which is statistically significant difference (p < 0.05). In the assessment of thrombotic disorders in a group with combination LA+ and APA+ statistical significance was indicated only in venous thromboses (p = 0.004). We can state from the results that in thrombotic disorders which can be seen in the framework of systemic tissue disorders positive LA and APA and a range of other factors such as activity of a basic disease, associated diseases, and treatment which can aggravate thrombotic disorders of individual patients can participate.
- MeSH
- antifosfolipidové protilátky krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lupusový inhibiční faktor koagulace krev MeSH
- samovolný potrat etiologie MeSH
- senioři MeSH
- systémový lupus erythematodes krev komplikace imunologie MeSH
- trombóza etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antifosfolipidové protilátky MeSH
- lupusový inhibiční faktor koagulace MeSH
