BACKGROUND: Idiopathic retroperitoneal fibrosis is characterized by the development of inflammatory infiltrates with marked fibrosis along the large retroperitoneal vessels. Rituximab in combination with glucocorticoids constitute an effective therapy, but the responses are not long-lasting. In other similar situations, addition of cyclophosphamide to the combination achieved longer and deeper responses. This was the reason to use the triple combination in this case. CASE: A 56-year-old man came with four weeks lasting abdominal pain with CT finding of retroperitoneal fibrosis with unilateral ureteral occlusion. Biopsy confirmed retroperitoneal fibrosis with histological findings of IgG4-associated disease. Treatment with prednizone was poorly tolerated. Therefore, the patient was switched to the combination of rituximab 375 mg/m2 on day 1, cyclophosphamide 300 mg/m2 in infusion in days 1 and 15, plus dexamethasone 20 mg in infusion on days 1 and 15, repeated in a 28-day cycle. RESULTS: Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) examination after 4 months of treatment showed a marked decrease in FDG accumulation and complete disappearance of the fibrotic mass. After 8 months, the induction therapy was followed by maintenance therapy with rituximab 1,000 mg plus dexamethasone 20 mg in 6-month intervals. Control PET/MR examination after 3 years is consistent with complete remission. The number of circulating plasmablasts correlated with the disease activity. CONCLUSION: Treatment of retroperitoneal fibrosis with the tripple combination of rituximab, cyclophosphamide and dexamethasone achieved a very rapid disappearance of pathological FDG accumulation and fibrotic retroperitoneal mass, with complete disappearance achieved after 4 months of treatment. After 3 years of maitenance therapy, the diesease is still in complete remission on PET/MR examination. We suggest to continue the maintenance therapy with rituximab because of some increase in the number of circulating plasmablasts after prolongation of the intervals between rituximab administration.

• Klíčová slova
• Cyclophosphamide, IgG4-related disease, circulating plasmablasts, cyclophosphamide, retroperitoneal fibrosis, rituximab,
• MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   MeSH
• dexamethason * terapeutické užití   aplikace a dávkování   MeSH
• fluorodeoxyglukosa F18 * MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• PET/CT MeSH
• retroperitoneální fibróza * farmakoterapie   diagnostické zobrazování   MeSH
• rituximab * terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• cyklofosfamid * MeSH
• dexamethason * MeSH
• fluorodeoxyglukosa F18 * MeSH
• rituximab * MeSH

INTRODUCTION: Multiple myeloma (MM) is a neoplastic disease caused by clonal proliferation of plasma cells in the bone marrow. The median age of newly diagnosed patients is 69 years. Bone involvement occurs in most patients during the course of the disease. The management of bone involvement in MM includes surgical intervention. Bones affected by osteolytic lesions are weakened and require stabilization through implants or endoprostheses. The intramedullary osteosynthesis method appears to be an ideal choice for stabilizing osteolytic lesions in long bones. The aim of our study was to analyze whether prophylactic fixation of these lesions improves the quality of life of the patients and has any impact on bone changes. METHODS: Patients undergoing prophylactic intramedullary osteosynthesis were operated on at the University Hospital Brno between 2013 and 2023. Patients included in this study had osteolytic lesions in long bones, Mirels' score equal to or greater than 8, and a minimum follow-up of 12 months. We evaluated the intensity of pain using a visual analog scale (VAS) assessed before the operation, after the operation, and one-year post-operation. The Musculoskeletal Tumour Society score (MSTS) score was assessed just before the planned stabilization procedure and one year later. RESULTS: At the time of the assessment, a statistically significant difference was found between the VAS score before the operation and 14 days post-operation (p.

• Klíčová slova
• multiple myeloma, Kahler-Pick law, bone metastases, intramedullary stabilization, osteolytic deposit, osteolytic lesion, prophylactic stabilization,
• MeSH
• intramedulární fixace fraktury metody   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * komplikace   chirurgie   MeSH
• osteolýza etiologie   prevence a kontrola   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Waldenström's macroglobulinemia (WM) is a very rare disease with an incidence 10times lower than that of multiple myeloma. The incidence of WM is also significantly lower than that of the other CD20+ low-grade lymphomas. The rarity of WM is the reason why registration studies of new drugs used for multiple myeloma or the more common CD20+low-grade lymphomas do not cover WM. Data on the efficacy of proteasome inhibitors in WM can be drawn from case descriptions, small series of patients and a few phase II clinical trials. The aim of this case report and review is to inform about our experience with the treatment of WM with bortezomib and then ixazomib and to present an overview of publications on proteasome inhibitors in WM. CASE: We describe a patient who, after 8 years of asymptomatic course of WM, had the first fulminant progression with severe pancytopenia at the age of 74 years. For the first-line treatment, he was treated with dexamethasone and rituximab, and after alleviation of pancytopenia, with bendamustine. Monoclonal immunoglobulin IgM (M-IgM) dropped from 40 g/L to the level as low as 6.9 g/L, which meant partial remission (PR) accompanied with normal blood count values. After 29 months of PR, the patient experienced a fulminant relapse of WM, accompanied by severe pancytopenia. Rituximab and dexamethasone were the backbone of treatment with addition of bortezomib for its significantly lower myelosuppression compared to alkylating agents. Treatment with the triple combination of bortezomib, rituximab, and dexamethasone was effective, however, after five cycles, bortezomib had to be discontinued for severe neurotoxicity. The sixth cycle contained rituximab and dexamethasone, and from the seventh cycle, ixazomib was started. The patient underwent seven cycles (months) of treatment consisting of ixazomib, rituximab and dexamethasone (14 cycles of treatment in total). RESULTS: M-IgM decreased from 30 g/L at the beginning of the treatment to 4.0 g/L at the end of treatment and further decreased to a value of 2.8 g/L at the eighth month after the end of the treatment. A deeper decrease in M-IgM than after first-line treatment was achieved and the patient now meets the criteria for a very good partial remission. CONCLUSION: According to the described experience and according to the review of publications evaluating proteasome inhibitors in WM, the combination of ixazomib with rituximab and dexamethasone excels with very good tolerance and high efficacy, approaching the efficacy of the combination of rituximab with bendamustine. This combination has its place particularly in patients with WM and cytopenia.

• Klíčová slova
• Waldenström’s macroglobulinemia, bortezomib, ixazomib,
• MeSH
• bortezomib * terapeutické užití   aplikace a dávkování   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• glycin * analogy a deriváty   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory proteasomu * terapeutické užití   MeSH
• lidé MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• recidiva MeSH
• rituximab * terapeutické užití   aplikace a dávkování   MeSH
• senioři MeSH
• sloučeniny boru * terapeutické užití   aplikace a dávkování   MeSH
• Waldenströmova makroglobulinemie * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• bortezomib * MeSH
• dexamethason * MeSH
• glycin * MeSH
• inhibitory proteasomu * MeSH
• ixazomib MeSH Prohlížeč
• rituximab * MeSH
• sloučeniny boru * MeSH

BACKGROUND: Rituximab is already a standard part of the treatment of patients with Waldenström's macroglobulinemia. However, a small proportion of patients develop intolerance to rituximab during administration or the treatment is not very effective. In these patients, we are faced with the question of whether another anti-CD20 monoclonal antibody can be used and what result will be achieved. PATIENT POPULATION AND METHODS: Between 2020 and 2022, we administered the new anti-CD20 monoclonal antibody obinutuzumab in combination with bendamustine and dexamethasone in five patients with Waldenström's macroglobulinemia (WM). All patients completed eight cycles of the indicated treatment. Two of them received second-line treatment, another two received third-line treatment, and one patient received this treatment as part of fourth-line treatment. We did not observe significant toxicity (grade III and IV) in any patient. RESULTS: All five patients achieved a deeper treatment response (once complete response, 4-times very good partial response) than in previous lines of treatment. At a median follow-up after treatment of 29 months (range 28-48), the disease relapsed in one patient only, the others are in remission. CONCLUSION: Obinutuzumab in combination with bendamustine is a very effective treatment alternative for WM. In the described five patients, obinutuzumab with bendamustine and dexamethasone achieved a deeper therapeutic response than the previous treatment lines. Obinutuzumab represents a drug that will be of great benefit to selected patients with WM.

• Klíčová slova
• Waldenström macroglobulinemia, bendamustine, obinutuzumab,
• MeSH
• bendamustin hydrochlorid * aplikace a dávkování   terapeutické užití   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Waldenströmova makroglobulinemie * farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bendamustin hydrochlorid * MeSH
• dexamethason * MeSH
• humanizované monoklonální protilátky * MeSH
• obinutuzumab MeSH Prohlížeč

The level of cardiorespiratory capacity, as measured by maximum VO(2)max oxygen consumption, is a significant factor related to the risk of metabolic syndrome, coronary heart disease and other health disorders. A total cohort of 2901 examinations was divided into 5 groups according to the nature of physical activity: group A - endurance athletes, group B - team sports players, group C - other competitive athletes, group D - recreational leisure-time athletes, group E - people with health problems. Cardiorespiratory fitness was assessed according to the VO(2)max and METmax parameters found in the stress test on a bicycle ergometer. A gradually increased load until exhaustion was used. While in groups A to D cases that would be classified as NYHA 1 (METmax lower than 9) were quite rare (10 cases out of 2777, i.e. 0.3 %), in groups E it was 20 % in men (16 cases out of 82) and 52 % in women (23 cases out of 44) of those examined. Accordingly, fitness age in groups A, B and C generally corresponded to a lower age than the calendar age, in groups E of both men and women, fitness age was significantly higher compared to the calendar age. High fitness age represents a significant risk of morbidity in relation to non-communicable diseases and probably also a significant limitation of their quality of life in later age.

• MeSH
• cvičení MeSH
• kvalita života * MeSH
• lidé MeSH
• morbidita MeSH
• předčasná smrt * MeSH
• rizikové faktory MeSH
• spotřeba kyslíku MeSH
• tělesná výkonnost MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Waldenström macroglobulinemia (WM) is a lymphoplasmocytic lymphoma with immunoglobulin M monoclonal protein. The incidence of this disease is very low (0.4/100,000), so that this disease can be regarded as an orphan's disease. It means that new drugs are often tested and registered for more frequent diseases. PURPOSE: In this review we will focus on the efficacy of the new drugs for WM. RESULTS: The current treatment options for symptomatic WM patients include alkylating agent cyclophosphamide and anti-CD20 monoclonal antibodies. Therapy with rituximab and bendamustin resulted in longer therapeutic response then therapy with rituximab, cyclophosphamide and dexamethasone. Many drugs, used in multiple myeloma (MM), shoved promising results in WM patients. Bortezomib is effective in WM, but its neurotoxicity is higher in WM than in MM patients. Therefore, new proteasome inhibitors, carfilzomib and ixazomib, are better tolerated as documented in several studies. New types of antiCD20 antibody (obinutuzumab) can be used in patients with rituximab intolerance. in five of our patients with WM, obinutuzumab and bendamustin reached deeper responses than therapies administered in previous lines of therapy. Oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab have extended the treatment options for WM patients. New BTK inhibitors (e. g. acalabrutinib, zanubrutinib, and vecabrutinib) were tested and their lower toxicity (atrial fibrillation) was documented. Moreover, the BCL2 inhibitor venetoclax is newly tested. CONCLUSION: New antiCD20 antibody (obinutuzumab) is of advantage in patients with WM with rituximab intolerance as well as bendamustin and new proteasome inhibitors (ixazomib and carfilzomib) or new BTK inhibitors with lower cardiotoxicity. Many of the abovementioned drugs do not have official registration for WM and can be administrated with the consent of the health care provider only. Thus, this work brings evidence of their efficacy.

• Klíčová slova
• Waldenström macroglobulinemia, bendamustin, carfilzomib, ibrutinib, ixazomib, obinutuzumab,
• MeSH
• antitumorózní látky * terapeutické užití   MeSH
• bendamustin hydrochlorid terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• inhibitory proteasomu terapeutické užití   MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• rituximab terapeutické užití   MeSH
• Waldenströmova makroglobulinemie * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky * MeSH
• bendamustin hydrochlorid MeSH
• cyklofosfamid MeSH
• inhibitory proteasomu MeSH
• ixazomib MeSH Prohlížeč
• monoklonální protilátky MeSH
• rituximab MeSH

BACKGROUND: The treatment of aggressive multiple myeloma (MM) patients, resistant to several treatment modalities, is very difficult in the real-world-evidence conditions. Ixazomib is a second-generation oral proteasome inhibitor. In combination with lenalidomide and dexamethasone, it is an effective and low-toxic treatment regimen for patients with relapsed or refractory MM. OBSERVATION: The presented case reports of two patients with an aggressive course of MM demonstrate the surprising effectiveness of this regimen. CONCLUSION: Repeated treatment with a combination of proteasome inhibitors (ixazomib) and immunomodulatory drugs (lenalidomide) may lead to significant clinical benefit in some patients and should be considered even in end-stage disease patients.

• Klíčová slova
• Kahler-Pick law, Multiple myeloma, ixazomib, leukaemia, leukemia, plasmacytoma, retreatment,
• MeSH
• dexamethason terapeutické užití   MeSH
• inhibitory proteasomu terapeutické užití   MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   etiologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• dexamethason MeSH
• inhibitory proteasomu MeSH
• ixazomib MeSH Prohlížeč
• lenalidomid MeSH

BACKGROUND: Lenalidomid ranks among immunomodulatory drugs. There are a few of the more common side effects, like a higher risk of venous trombembolism or diarrhea. Other side effects are rare. The hyperbilirubinemia described in this article can be assigned to them. In our case, the increase of bilirubin was associated with unrecognized Gilbert syndrome. CASE DESCRIPTION: We report a patient with multiple myeloma and necrobio-tic xanthogranuloma (NXG) of the skin and liver. After the treatment with bortezomib, lenalidomid and dexamethasone, complete remission was attained after 4 cycles with decrease of monoclonal immunoglobulin to an unmeasurable concentration. At the same time, the dis-appearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT was evident. The administration of bortezomib was stopped after 8 cycles and only continued with lenalidomide as a maintenance therapy. However, after four cycles of this therapy, bilirubin increased above the upper limit and the increase continued till the 11th month of lenadomide administration, when bilirubin reached the highest concentration of 75 μmol/l (more than the three-fold of the upper limit, grade III toxicity). The patient had asymptomatic hyperbilirubinemia with no underlying liver disease or renal impairment while being on lenalidomide therapy. Genetic studies proved mutation; insertion in the promotor gene UGT1A1 typical for Gilbert syndrome. Hyperbilirubinemia may be attributed to the unmasking of previously undia-gnosed Gilbert syndrome. Therefore, the therapy with lenalidomide was interrupted after 11 months. The bilirubin level decreased after the discontinuation of the drug. CONCLUSION: NXG disappeared after fulfilling complete remission of multiple myeloma with disappearance of monoclonal immunoglobulin. This observation supports the hypothesis that monoclonal immunoglobulin has a crucial role in the ethiopathogenesis of NXG and suggests the treatment of monoclonal gammopathy if present in a patient with NXG, hoping that this will result in xantogranuloma disappearance.

• Klíčová slova
• Gilbert syndrome, Kahler-Pick law, Multiple myeloma, hyperbilirubinemia, monoclonal Gilbert syndrome, necrobio­tic xanthogranuloma,
• MeSH
• bilirubin MeSH
• bortezomib terapeutické užití   MeSH
• dexamethason terapeutické užití   MeSH
• Gilbertova nemoc * farmakoterapie   MeSH
• hyperbilirubinemie farmakoterapie   MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   patologie   MeSH
• nekrobiotický xantogranulom * diagnóza   farmakoterapie   MeSH
• PET/CT MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• bilirubin MeSH
• bortezomib MeSH
• dexamethason MeSH
• lenalidomid MeSH

Monoclonal gammopathy of undetermined significance (MGUS) is a known precursor of more serious cancers, such as multiple myeloma (MM), Waldenström macroglobulinemia (MW) and other lymphoproliferative disorders. Using 18F-FDG PET/CT, we aimed to evaluate its benefit in early detection of various accompanying disorders and illnesses in MGUS patients. We prospectively analyzed the diagnostic relevance of 18F-FDG PET/CT in 390 newly diagnosed MGUS patients. On 18F-FDG PET/CT scans, the presence of focal or diffuse areas of detectable increased tracer uptake was recorded in 37 (9.5%) MGUS patients. The most frequent pathology was lymphadenopathy (3.8%), followed by thyroid diseases (2.1%), rheumatic diseases (1.8%), and other solid malignancies (1.5%). These results have major implications for confirmed associations of MGUS with numerous malignant and non-malignant disorders. We believe that 18F-FDG PET/CT imaging in newly diagnosed MGUS patients may be useful in early detection of other serious pathologies, not only in predicting progression of MGUS to active MM, and should be strongly recommended if available.

• MeSH
• dospělí MeSH
• fluorodeoxyglukosa F18 MeSH
• lidé MeSH
• mnohočetný myelom * diagnostické zobrazování   MeSH
• monoklonální gamapatie nejasného významu * diagnostické zobrazování   MeSH
• PET/CT MeSH
• pozitronová emisní tomografie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluorodeoxyglukosa F18 MeSH

Nowadays, bortezomib, a proteasome inhibitor, is widely used in treatment of newly diagnosed or relapsed multiple myeloma. The aim of this study was to analyze efficiency of bortezomib retreatment in patients with relapsed or refractory multiple myeloma. From 2004 to 2016, 283 patients were retrospectively evaluated at all hematological centers in the Czech Republic. Bortezomib was administered at the standard dosing and in combined therapy with corticosteroids, chemotherapy or thalidomide. Before bortezomib retreatment, 61% of patients received previous lenalidomide treatment, 40.6% autologous transplantation, and median number of prior lines of therapy was three. In total, 21% of patients were refractory to the first bortezomib treatment. In bortezomib retreatment, overall response rate was 34.5%, median progression-free survival was 7.8 months (95% CI: 6.7-8.9), median duration of response was 10.5 months (95% CI: 8.0-13.0) and median overall survival was 20.3 months (95% CI: 17.9-22.7). Grade 3-4 adverse events included thrombocytopenia, neutropenia, anemia and infection. Neuropathy grade 2 or higher occurred in 19.4% of patients. We conclude that bortezomib retreatment is an effective and safe therapeutic alternative for relapsed or refractory multiple myeloma patients.

• MeSH
• bortezomib terapeutické užití   MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   MeSH
• opakovaná terapie MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• bortezomib MeSH