BACKGROUND: In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. METHODS: Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. RESULTS: The median number of HCO hemodialysis sessions was 11 (range 1-42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. CONCLUSION: The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.

• MeSH
• Acute Kidney Injury * diagnosis   therapy   MeSH
• Bortezomib adverse effects   MeSH
• Renal Dialysis adverse effects   MeSH
• Immunoglobulin Light Chains MeSH
• Humans MeSH
• Multiple Myeloma * complications   diagnosis   drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article 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 therapeutic use   MeSH
• Humans MeSH
• Multiple Myeloma drug therapy   MeSH
• Retreatment MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

OBJECTIVE: To predict the real-world (RW) cost-effectiveness of carfilzomib in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in relapsed multiple myeloma (MM) patients after one to three prior therapies. METHODS: A partitioned survival model that included three health states (progression-free, progressed disease and death) was built. Progression-free survival (PFS), overall survival (OS) and time to discontinuation (TTD) data for the Rd arm were derived using the Registry of Monoclonal Gammopathies in the Czech Republic; the relative treatment effects of KRd versus Rd were estimated from the phase 3, randomised, ASPIRE trial, and were used to predict PFS, OS and TTD for KRd. The model was developed from the payer perspective and included drug costs, administration costs, monitoring costs, palliative care costs and adverse-event related costs collected from Czech sources. RESULTS: The base case incremental cost effectiveness ratio for KRd compared with Rd was €73,156 per quality-adjusted life year (QALY) gained. Patients on KRd incurred costs of €117,534 over their lifetime compared with €53,165 for patients on Rd. The QALYs gained were 2.63 and 1.75 for patients on KRd and Rd, respectively. CONCLUSIONS: Combining the strengths of randomised controlled trials and observational databases in cost-effectiveness models can generate policy-relevant results to allow well-informed decision-making. The current model showed that KRd is likely to be cost-effective versus Rd in the RW and, therefore, the reimbursement of KRd represents an efficient allocation of resources within the healthcare system.

• MeSH
• Cost-Benefit Analysis * MeSH
• Dexamethasone pharmacology   MeSH
• Quality-Adjusted Life Years MeSH
• Lenalidomide pharmacology   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   etiology   MeSH
• Multiple Myeloma drug therapy   etiology   mortality   MeSH
• Drug Costs MeSH
• Oligopeptides pharmacology   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Registries MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Czech Republic MeSH

The main goal was to find a simple prognostic to evaluate overall survival of patients older than 65 years of age with myeloma. Retrospective registry-based analysis from the Registry of Monoclonal Gammopathies was conducted. Patients over 65 years with symptomatic myeloma were included. The four major parameters with impact on survival were identified: male gender, age > 75, creatinine > 152 μmol/L, and ECOG performance status 2-4. The patients were scored as good (0 points), intermediate good (1 point), intermediate poor (2 points), poor (3-4 points). Patients (1410 MM) were included. Median OS (months) was 65.7 (95% CI 49.8-81.7) for good, 51.0 (44.1-57.8) for intermediate good, 32.2 (26.2-38.2) for intermediate poor, and 18.9 (15.1-22.7) for poor. The differences in OS were statistically significant (p < 0.0001). Good score was used as reference for hazard ratios, which for each other score were 1.43 (1.09-1.84) for intermediate good, 2.58 (2.00-3.33) for intermediate poor, and 3.88 (2.94-5.10) for poor. Time to progression showed medians (months) 20.5 (17.4-62.4) for good, 19.3 (17.0-21.7) for intermediate good, 19.6 (16.2-23.0) for intermediate poor, and 13.0 (10.8-15.2) for poor. The suggested scoring system provides readily available information about the prognosis of MM patients above 65 years.

• MeSH
• Humans MeSH
• Survival Rate MeSH
• Multiple Myeloma mortality   therapy   MeSH
• Disease-Free Survival MeSH
• Registries * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Age Factors MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH

Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs Rd after first relapse (HR 0.713) and a 9-month improvement after ⩾2 previous lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15-month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month improvement in lenalidomide-exposed patients (HR 0.796). Objective response and complete response or better rates were higher with KRd vs Rd, irrespective of previous treatment. KRd had a favorable benefit-risk profile and should be considered an appropriate treatment option for patients with 1 or ⩾2 previous lines of therapy and those previously exposed to bortezomib, thalidomide or lenalidomide.

• MeSH
• Dexamethasone administration & dosage   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   pathology   MeSH
• Multiple Myeloma drug therapy   pathology   MeSH
• Oligopeptides administration & dosage   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols administration & dosage   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Thalidomide administration & dosage   analogs & derivatives   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Transplantation, Autologous immunology   MeSH
• Adult MeSH
• Immunoglobulin Light Chains MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Stem Cell Transplantation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

Primary mediastinal B-cell lymphoma (PMBL) seems to be reliably distinguished from diffuse large B-cell lymphoma (DLBCL) with microarray technology. We measured expression of Fcer2, Pdl2 and Blk genes using real-time quantitative polymerase chain reaction (RTqPCR) on formalin fixed, paraffin embedded material (FFPE) and suggested a formula to discriminate PMBL from DLBCL. For 39/82 included patients the diagnosis of PMBL was expected clinico-pathologically. Diagnosis of 10/39 and 2/43 of clinically considered PMBLs and DLBCLs, respectively, was not genetically confirmed. Compared to confirmed PMBLs, unconfirmed ones showed clinical features similar to DLBCLs, e.g. spleen infiltration (p=0,028) and decreased invasiveness in pericardium (p=0,045). They tended to have more common infradiaphragmatic involvement, less often tumor sclerosis or fluidothorax. There were no immunohistochemical differences between genetically confirmed and unconfirmed PMBLs. New approach of distinguishing PMBL and DLBCL is presented. It is based on expression of three genes in routinely available FFPE material using RTqPCR.

• MeSH
• Lymphoma, B-Cell diagnosis   MeSH
• Diagnosis, Differential MeSH
• Lymphoma, Large B-Cell, Diffuse diagnosis   MeSH
• Adult MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Mediastinal Neoplasms diagnosis   MeSH
• Polymerase Chain Reaction methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Histiocytosis MeSH
• Skin Diseases MeSH
• Humans MeSH
• Necrobiotic Disorders pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Case Reports MeSH

Autoři podávají podrobný rozbor desetiletého sledování dětského pacienta s conjunctivitis lignea. Dokládají přítomnost všech, typických očních nálezů (zejména rekurentní tvorbu granulomatózních pseudotumorů postižené sliznice) souvisejících s touto vzácnou chronickou pseudomembranózní konjunktivitidou. Klinický obraz zahrnuje i deficit plazminogenu, který je nově pokládán za primární příčinu onemocnění. Diagnóza byla potvrzena při opakovaných excizích histologicky. Typický je pseudomembranózní zánět se smíšeným zánětlivým infHtrátem, který obsahuje velké množství elementů chronické i akutní zánětlivé reakce. Součástí zánětlivého obrazuje granulom s akumulací PAS-pozitivní amorfní hmoty s vysokým obsahem fibrinu a bohatou novotvořenou cévní sítí. Na základě postupně odhalovaných poznatků o možné etiopatogenezi onemocnění se odvíjel i léčebný postup v daném období. Celkově až devátý, poslední, chirurgický výkon přinesl dlouhodobou remisi trvající již třicet měsíců. Autoři kombinovali snesení granulomu s aplikací mitomycinu na rannou plochu, kterou překryli plastikou spojivky. V pooperačním období aplikovali heparin v masti s kortikosteroidy a antibiotiky. Cílem podání mitomycinu je zpomalení fibroproliferativní reparativní reakce. Překrytí ranné plochy snižuje počet mikrotraumat na nerovné pooperační sklerální ploše. Heparin v tkáňovém intersticiu ranné plochy blokuje konverzi fibrinogenu na fibrin.

Authors refer about detailed analysis of ten years follow up of a child patient with ligneous conjunctivitis. They document presence of all typical eye findings (especially recurrent formation of granulomatous pseudotumors in affected mucous membrane) related to this rare pseudomembranous conjunctivitis. The clinical picture of the disease includes plasminogen deficiency, a factor newly considered as primary cause of the disease. The diagnosis was confirmed histologicaly by repeated probatory excisions. Pseudomembranous inflammation with mixed inflammatory infiltrate containing large amount of elements of chronical as well as acute inflammatory reaction is typical. Granuloma with the accumulation of the PASpositive amorphous matrix with high content of the fibrin and with the network of newly formed vessels is the component of the inflammatory picture. The treatment was based on successively discovered knowledge of the possible etiopathogenesis of the disease. Only the ninth, last surgical procedure induced longer-term remission, which lasts sixteen months until now. The granuloma excision was combined with the mitomicin application on the wound surface and a conjunctivoplasty. During the postoperative period, the ointment with heparin, corticosteroid and antibiotic was applied. The purpose of the mitomicin use is to slow down the fibroproliferative reparative reaction. Covering of the wound surface decreases the number of microtraumas on the uneven postoperative scleral surface. Heparin in the interstitial tissue of the wound surface blocks the conversion of fibrinogen to fibrin.

• MeSH
• Child MeSH
• Granuloma etiology   drug therapy   surgery   MeSH
• Heparin administration & dosage   pharmacology   MeSH
• Clinical Laboratory Techniques statistics & numerical data   MeSH
• Conjunctivitis diagnosis   pathology   therapy   MeSH
• Humans MeSH
• Mitomycin administration & dosage   pharmacology   MeSH
• Plasminogen deficiency   MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

Primární nitrooční lymfom (PNL) se řadí k primárním lymfomům centrálního nervového systému (CNS). Nádorové buňky při něm infiltrují tkáně oka, zejména sítnici, zrakový nerv a pronikají do sklivce. Obraz v oku často imituje nitrooční zánět, a proto toto onemocnění patří k tzv. maskujícím syndromům. Nitrooč¬ní lymfom se může projevit jako izolované onemocnění oka, ale často je v době stanovení oční diagnózy patrná diseminace do jiných tkání, zejména do CNS. Diagnóza PNL vyžaduje odběr a cytologický rozbor sklivce s průkazem maligních elementů. Léčba PNL závisí na stupni diseminace do organismu. Systémové onemocnění se léčí systémovou chemoterapií kombinovanou s radioterapií, léčba izolovaného očního one¬mocnění je dosud kontroverzní. Vedle radioterapie orbity je jednou z terapeutických možností aplikace metotrexátu v netoxických dávkách do sklivce postiženého oka. Tento zákrok může někdy pomoci získat kontrolu nad tímto jinak potenciálně infaustním onemocněním.

Primary intraocular lymphoma (PIOL) is a subset of primary centra! nervous systém (CNS) lymphomas, in which tumour cells invade ocular tissues, such as the retina, the optic nerve and the vitreous. The clinical picture often resembles intraocular inflammation and thus this disease is part of so-called masquerading syndromes. Intraocular lymphoma can affect the eye only or disseminate to other tissues in the body, pre-ferentially to the CNS. For diagnosis, cytological detection of tumour cells of the vitreous or cerebrospinal fluid is necessary. Therapy depends on the dissemination of the disease. Systemic chemotherapy and radi-otherapy is ušed when systemic disease is confirmed, the treatment of isolated eye involvement is still con-troversial. Treatment options in isolated ocular lymphoma include orbital radiotherapy and/or intravitreal application of methotrexate in a non-toxic dose. This intervention can sometimes help to gain control over this potentially lethal disease.

• MeSH
• Antineoplastic Agents administration & dosage   pharmacology   MeSH
• Lymphoma, Large B-Cell, Diffuse diagnosis   drug therapy   radiotherapy   MeSH
• Humans MeSH
• Methotrexate administration & dosage   pharmacology   MeSH
• Central Nervous System Neoplasms diagnosis   secondary   MeSH
• Eye Neoplasms diagnosis   etiology   drug therapy   MeSH
• Retina pathology   MeSH
• Vitreous Body pathology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH