INTRODUCTION: Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. CASE DESCRIPTION: In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. CONCLUSION: Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.
- Klíčová slova
- POEMS syndrome, monoclonal gammopathy of clinical significance (MGCS) with osteosclerosis, osteosclerosis, osteosclerotic myeloma,
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * komplikace patologie diagnostické zobrazování MeSH
- osteoskleróza * diagnostické zobrazování etiologie patologie MeSH
- paraproteinemie komplikace patologie MeSH
- PET/CT MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- MeSH
- chromozomální delece MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 1 genetika MeSH
- mnohočetný myelom * komplikace diagnóza MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
The incidence of monoclonal gammopathy (MG) increases with age. In individuals over 80 years of age, we can diagnose the presence of monoclonal immunoglobulin (MIg) in up to 10 % of cases. Not only malignant diseases such as multiple myeloma (MM), but also benign forms such as MGUS (monoclonal gammopathy of undetermined significance) can lead to renal involvement. The light chains of immunoglobulins (LC) are the most damaging to the kidneys, as they are freely filtered into the urine due to their molecular weight. Detection of MIg relies mainly on a combination of immunofixation electrophoresis of serum (IELFO) and urine and determination of free light chains (FLC) of kappa and lambda and their ratio (κ/λ) in serum. The combination of these tests will detect the presence of MIg with 99 % sensitivity. Renal damage in MG may be caused by direct deposition of MIg in the glomeruli (e.g. AL amyloidosis, LC deposition disease) or tubules (in the distal tubule as a myeloma kidney or in the proximal tubule as Fanconi syndrome or proximal tubulopathy). Typical urinary findings in these diseases are moderate or severe proteinuria or nephrotic syndrome. Acute kidney injury (AKI) can be expected especially when serum FLC is >500 mg/l. Renal biopsy is crucial to establish an accurate diagnosis and thus initiate the correct treatment. Treatment of these types of renal damage involves the same treatment regimens used in the treatment of MM, including proteasome inhibitors or daratumumab.
- Klíčová slova
- monoclonal immunoglobulin, MGUS. multiple myeloma, AL amyloidosis, acute kidney injury, chronic kidney injury,
- MeSH
- lidé MeSH
- mnohočetný myelom * komplikace diagnóza MeSH
- nemoci ledvin etiologie diagnóza MeSH
- paraproteinemie * komplikace diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy 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
Cutaneous collagenous vasculopathy (CCV) is an extremely rare acquired microangiopathy of unknown etiology. The authors describe a case of a 68-year-old man, a carrier of a heterozygous pathogenic variant of the glucocerebrosidase (GBA) gene, who was diagnosed with CCV, revealing uncommon fibrinogen positivity in direct immunofluorescence. The patient was subsequently diagnosed with multiple myeloma. Treatment of the myeloma with combined chemotherapy including bortezomib, followed by autologous stem cell transplantation, led to significant reduction of cutaneous lesions. To the best of the authors' knowledge, this is the first published case of CCV in a carrier of a pathogenic variant of the GBA gene, associated with multiple myeloma and with significant regression of CCV after myeloma treatment. Direct immunofluorescence examination revealed an unusual fibrinogen deposition. Hypothetical causative role of bortezomib treatment was proposed regarding significant regression of CCV.
- Klíčová slova
- bortezomib, cutaneous collagenous vasculopathy, direct immunofluorescence, glucocerebrosidase gene, multiple myeloma,
- MeSH
- autologní transplantace MeSH
- bortezomib terapeutické užití MeSH
- fibrinogen terapeutické užití MeSH
- glukosylceramidasa terapeutické užití MeSH
- kožní cévní nemoci * patologie MeSH
- lidé MeSH
- mnohočetný myelom * komplikace farmakoterapie genetika MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- senioři MeSH
- teleangiektazie * patologie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- bortezomib MeSH
- fibrinogen MeSH
- glukosylceramidasa MeSH
Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The phase III IKEMA study (clinicaltrials gov. Identifier: NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) versus Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate <60 mL/min/1.73 m². Addition of Isa prolonged progression-free survival (PFS) in patients with RI (hazard ratio: 0.27; 95% confidence interval [CI]: 0.11-0.66; median PFS not reached for Isa-Kd versus 13.4 months for Kd [20.8-month follow-up]). Complete renal responses occurred more frequently with Isa-Kd (52.0%) versus Kd (30.8%) and were durable in 32.0% versus 7.7% of patients, respectively. Treatment exposure was longer with Isa-Kd, with median number of started cycles and median duration of exposure of 20 versus 9 cycles and 81.0 versus 35.7 weeks for Isa-Kd versus Kd, respectively. Among patients with RI, the incidence of patients with grade ≥3 treatment-emergent adverse events was similar between the two arms (79.1% in Isa-Kd vs. 77.8% in Kd). In summary, the addition of Isa to Kd improved clinical outcomes with a manageable safety profile in patients with RI, consistent with the benefit observed in the overall IKEMA study population.
- MeSH
- dexamethason škodlivé účinky MeSH
- humanizované monoklonální protilátky MeSH
- lidé MeSH
- mnohočetný myelom * komplikace farmakoterapie MeSH
- oligopeptidy MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- renální insuficience * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- Názvy látek
- carfilzomib MeSH Prohlížeč
- dexamethason MeSH
- humanizované monoklonální protilátky MeSH
- isatuximab MeSH Prohlížeč
- oligopeptidy MeSH
Patients with multiple myeloma frequently present with substantial immune impairment and an increased risk for infections and infection-related mortality. The risk for infection with SARS-CoV-2 virus and resulting mortality is also increased, emphasising the importance of protecting patients by vaccination. Available data in patients with multiple myeloma suggest a suboptimal anti-SARS-CoV-2 immune response, meaning a proportion of patients are unprotected. Factors associated with poor response are uncontrolled disease, immunosuppression, concomitant therapy, more lines of therapy, and CD38 antibody-directed and B-cell maturation antigen-directed therapy. These facts suggest that monitoring the immune response to vaccination in patients with multiple myeloma might provide guidance for clinical management, such as administration of additional doses of the same or another vaccine, or even temporary treatment discontinuation, if possible. In those who do not exhibit a good response, prophylactic treatment with neutralising monoclonal antibody cocktails might be considered. In patients deficient of a SARS-CoV-2 immune response, adherence to measures for infection risk reduction is particularly recommended. This consensus was generated by members of the European Multiple Myeloma Network and some external experts. The panel members convened in virtual meetings and conducted an extensive literature research and evaluated recently published data and work presented at meetings, as well as findings from their own studies. The outcome of the discussions on establishing consensus recommendations for COVID-19 vaccination in patients with multiple myeloma was condensed into this Review.
- MeSH
- COVID-19 prevence a kontrola MeSH
- konsensus MeSH
- lidé MeSH
- mnohočetný myelom komplikace farmakoterapie imunologie MeSH
- SARS-CoV-2 MeSH
- směrnice pro lékařskou praxi jako téma normy MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- vakcíny proti COVID-19 MeSH
Infections are the primary cause of morbidity and mortality in multiple myeloma (MM) patients (pts). The aim of our retrospective analysis was to evaluate incidence and course of COVID-19 infection in a cohort of 351 MM outpatients treated with novel drugs. COVID-19 disease was detected in 50/351 pts (14%); median age was 68 years. Gender, ISS stage, and last treatment lines were as follows: male 32, female 18; ISS-I 19, ISS-II 20, ISS-III 11; daratumumab-based 15, lenalidomide-based 12, bortezomib-based 17, other 6. Positive PCR test at COVID-19 diagnosis was present in all pts; anti-myeloma treatment was interrupted. Hospitalizations for COVID-19 pneumonia were necessary for 28/50 pts (56%), 18/50 pts (36%) in standard unit (SU) 10/50 pts (20%) in intensive care unit (ICU), and 9/50 pts (18%) died. The statistically significant parameters for COVID-19 hospitalization were as follows: responsive versus non-responsive disease (p = 0.027), ECOG performance status 0-2 versus ≥ 3 (p = 0.014), presence of comorbidities (0-1 versus ≥ 2, p = 0.043). The statistically significant factors for COVID-19 death were as follows: ECOG 0-2 versus ≥ 3 (p = 0.001), presence of comorbidities (0-1 versus ≥ 2, p = 0.007), serious course of COVID-19 disease with ICU hospitalization (SU versus ICU, p = 0.001). None of the other studied risk factors was associated with poor outcome (age, gender, ISS stage, immunoparesis, type of anti-myeloma treatment). Full recovery from COVID-19 infection was observed in 41/50 pts (82%) in median of 32 days. The course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths.
- Klíčová slova
- COVID-19, Hospitalization, Mortality, Multiple myeloma, Novel drugs,
- MeSH
- antitumorózní látky terapeutické užití MeSH
- bortezomib terapeutické užití MeSH
- COVID-19 komplikace diagnóza etiologie MeSH
- dospělí MeSH
- hospitalizace MeSH
- incidence MeSH
- lenalidomid terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom komplikace farmakoterapie MeSH
- monoklonální protilátky terapeutické užití MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 izolace a purifikace MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky MeSH
- bortezomib MeSH
- daratumumab MeSH Prohlížeč
- lenalidomid MeSH
- monoklonální protilátky MeSH
Necrobiotic xanthogranuloma (NXG) is a rare chronic condition, belonging to the group non-Langerhans cell histiocytoses, which is relevant due to the possibility of extracutaneous involvement and association with systemic diseases, particularly monoclonal gammopathy, MGUS and multiple myeloma. The case reported here NXG was diagnosed after 1 years of evolution in patient with asymptomatic multiple myeloma. After treatment with bortezomib, lenalidomid and dexamethasone, there was evident abrupt decrease of monoclonal immunoglobulin to not measurable level (complete remission of multiple myeloma) and in the same time was evident disappearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT. The etiopathogenetic association of monoclonal immunoglobulin with NXG is documented in this case report with disappearance of NXG in the time of disappearance of monoclonal immunoglobulin.
- Klíčová slova
- Kahler-Pick law, Multiple myeloma, monoclonal gammopathy, necrobiotic xanthogranuloma,
- MeSH
- bortezomib terapeutické užití MeSH
- dexamethason terapeutické užití MeSH
- imunoglobuliny MeSH
- lidé MeSH
- mnohočetný myelom * komplikace farmakoterapie MeSH
- nekrobiotický xantogranulom * komplikace diagnóza farmakoterapie MeSH
- PET/CT MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- bortezomib MeSH
- dexamethason MeSH
- imunoglobuliny MeSH
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.
- Klíčová slova
- Acute kidney injury, Bortezomib, Cast nephropathy, High-cut-off (HCO) hemodialysis, Multiple myeloma,
- MeSH
- akutní poškození ledvin * diagnóza terapie MeSH
- bortezomib škodlivé účinky MeSH
- dialýza ledvin škodlivé účinky MeSH
- lehké řetězce imunoglobulinů MeSH
- lidé MeSH
- mnohočetný myelom * komplikace diagnóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bortezomib MeSH
- lehké řetězce imunoglobulinů MeSH
