OBJECTIVES: In stress echocardiography (SE), dipyridamole (DIP) and dynamic stress (ExSE) are reported as being safer than dobutamine stress echocardiography (DSE). We investigated whether these commonly used stressors cause myocardial injury, measured by high sensitivity troponin T (hsTnT). METHODS: One hundred and thirty five patients (DSE n = 46, ExsE n = 46, DIP n = 43) with negative result of SE were studied. The exclusion criteria were known ischaemic heart disease (IHD), baseline wall motion abnormalities, left ventricle systolic dysfunction/regional wall motion abnormalities, septum/posterior wall ≥13 mm, diabetes/pre-diabetes, baseline hsTnT level ≥14 ng/L, baseline blood pressure ≥160/100 mmHg, peak pulmonary pressure ≥45mmHg, eGFR <1ml/s/1.73m2 , more than mild to moderate valvular disease and dobutamine side effects. HsTnT was measured before and 180 minutes after the test. RESULTS: All patients had low pre-test probabilities of having obstructive IHD. HsTnT increased in DSE, less so in ExSE, and was unchanged in the DIP group (∆hsTnT 9.4 [1.5-58.6], 1.1 [-0.9-15.7], -0.1 [-1.4-2.1] ng/L, respectively, p<0.001). In DSE, the ∆hsTnT was associated with peak dobutamine dose (r = 0.30, p = 0.045), test length (r = 0.43, p = 0.003) and atropine use (p<0.001). In ExSE, the hsTnT increase was more likely in females (p = 0.012) and the elderly (>65 years) (r = 0.32, p = 0.03); no association was found between atropine use (p = 0.786) or test length and ∆hsTnT (r = 0.10, p = 0.530). CONCLUSIONS: DSE is associated with myocardial injury in patients with negative SE, no injury was observed in DIP and only mild case in ExSE. Whether myocardial injury is causative of the higher reported adverse event rates in DSE remains to be determined.
- Klíčová slova
- hsTnT, myocardial injury, negative stress echocardiography,
- MeSH
- deriváty atropinu MeSH
- dipyridamol MeSH
- dobutamin MeSH
- echokardiografie MeSH
- ischemická choroba srdeční * komplikace MeSH
- kardiotonika MeSH
- lidé MeSH
- nemoci koronárních tepen * komplikace MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- zátěžová echokardiografie MeSH
- zátěžový test MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- deriváty atropinu MeSH
- dipyridamol MeSH
- dobutamin MeSH
- kardiotonika MeSH
AIM: This study compared the results of nivolumab treatment in patients with pulmonary adenocarcinomas based upon previous chemotherapeutic regimens. PATIENTS AND METHODS: The data source for this retrospective study was the Czech VILP registry of patients with nivolumab-treated adenocarcinomas in second and higher lines of treatment. In relation to objective response rate, progression-free interval, and overall survival, three comparisons of patient were made: A: Those treated in first line with cisplatin and pemetrexed versus carboplatin with paclitaxel or vinorelbine; B: treatment with cisplatin and pemetrexed versus carboplatin with paclitaxel/vinorelbine and bevacizumab; and C: treatment in previous lines with pemetrexed (first-line cisplatin and pemetrexed plus those treated in second line with pemetrexed) versus treatment with taxane (first-line carboplatin and paclitaxel only plus those treated with second-line docetaxel). RESULTS: We observed no differences in objective response rate or progression-free survival between patients treated with the stated chemotherapeutic regimens. We observed a trend towards better overall survival for patients treated with carboplatin plus taxanes or vinorelbine with/without bevacizumab. CONCLUSION: From our overall survival data, a chemotherapeutic regimen of carboplatin plus taxanes or vinorelbine with/without bevacizumab might be a better partner for immunotherapy than a cisplatin and pemetrexed-based one.
- Klíčová slova
- NSCLC, chemotherapy, lung cancer, nivolumab, overall survival, pemetrexed, taxanes, vinorelbine,
- MeSH
- lidé MeSH
- nádory plic * patologie MeSH
- nemalobuněčný karcinom plic * patologie MeSH
- nivolumab terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nivolumab MeSH
Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4·38, 95% confidence interval (CI): 2·46-7·80, P < 0·0001], high lactate dehydrogenase (LDH) levels (>5 μkat/l; OR 2·07, 95% CI: 1·51-2·84, P < 0·0001), extensive osteolytic activity (OR 2·21, 95% CI: 1·54-3·15, P < 0·001), and immunoglobulin A (IgA; OR 1·53, 95% CI: 1·11-2·11, P = 0·009) or the non-secretory type of MM (OR 2·83; 95% CI: 1·32-6·04, P = 0·007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression-free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13·8 months (95% CI: 11·4-16·3) vs 18·8 months (95% CI: 17·7-19·9), P = 0·006; mOS: 26·7 months (95% CI: 18·1-35·4) vs 58·7 months (95% CI: 54·8-62·6), P < 0·001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.
- Klíčová slova
- extramedullary disease, multiple myeloma, prognostic factors,
- MeSH
- analýza přežití MeSH
- lidé MeSH
- mnohočetný myelom mortalita patofyziologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Due to modern genomic techniques, the involvement of lncRNAs in tumorigenesis has been revealed; however, information concerning lncRNA interplay in multiple myeloma (MM) and plasma cell leukemia (PCL) is virtually absent. Herein, we aimed to identify the lncRNAs involved in MM to PCL progression. We investigated representative datasets of MM and PCL patients using next-generation sequencing. In total, 13 deregulated lncRNAs (p < 0.00025) were identified; four of them were chosen for further validation in an independent set of MM and PCL patients by RT-qPCR. The obtained results proved the significant downregulation of lymphocyte antigen antisense RNA 1 (LY86-AS1) and VIM antisense RNA 1 (VIM-AS1) in PCL compared to MM. Importantly, these two lncRNAs could be involved in the progression of MM into PCL; thus, they could serve as promising novel biomarkers of MM progression.
- Klíčová slova
- biomarkers, disease progression, long non-coding RNA, multiple myeloma, next-generation sequencing, plasma cell leukemia,
- Publikační typ
- časopisecké články MeSH
- MeSH
- indukce remise MeSH
- lehké řetězce imunoglobulinů MeSH
- lidé MeSH
- mnohočetný myelom * MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- Názvy látek
- lehké řetězce imunoglobulinů MeSH
Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated. The phenotypic profile of the PCs was also analysed to determine if there is an association with clinical outcomes and to evaluate the prognostic value of analysed markers. Our results revealed that FC is an excellent method for identifying circulating PCs as a significantly higher number was identified by FC than by morphology (26·7% vs. 13·5%, P = 0·02). None of secondary PCL cases expressed CD19 or CD20. A low level of expression with similar positivity of CD27, CD28, CD81 and CD117 was found in both PCL groups. A decrease of CD44 expression was detected only in secondary PCL. Expression of CD56 was present in more than half of PCL cases as well as cytoplasmic nestin. A decreased level of platelets, Eastern Cooperative Oncology Group score of 2-3 and lack of CD20+ PC were associated with a higher risk of death. FC could be incorporated in PCL diagnostics not only to determine the number of circulating PCs, but also to assess their phenotype profile and this information should be useful in patients' diagnosis and possible prognosis.
- Klíčová slova
- flow cytometry, multiple myeloma, phenotype, plasma cell, plasma cell leukaemia, prognosis,
- MeSH
- antigeny nádorové analýza MeSH
- buňky kostní dřeně chemie MeSH
- časná detekce nádoru MeSH
- CD antigeny analýza MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- falešně negativní reakce MeSH
- imunofenotypizace MeSH
- Kaplanův-Meierův odhad MeSH
- kostní dřeň patologie MeSH
- krevní obraz * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové cirkulující buňky * MeSH
- plazmatické buňky * chemie ultrastruktura MeSH
- plazmocelulární leukemie krev mortalita MeSH
- průtoková cytometrie metody MeSH
- senioři nad 80 let MeSH
- senioři 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
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antigeny nádorové MeSH
- CD antigeny MeSH
OBJECTIVES: This study compared the use of bortezomib in different combination regimens in newly diagnosed multiple myeloma (NDMM) patients who were transplant ineligible. PATIENTS AND METHODS: We analyzed data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group (CMG) to provide real-world evidence of outcome for 794 newly diagnosed MM transplant ineligible patients. The most frequently used regimen was VCd (bortezomib-cyclophosphamide-dexamethasone) (47.5%) over VMP (bortezomib-melphalan-prednisone) (21.7%), BDd (bortezomib-doxorubicin-dexamethasone) (9.8%), and VTd (bortezomib-thalidomide-dexamethasone) (2.9%). RESULTS: The overall response rate (ORR) was 69.2% (478/691), including 12.6% (≥ CR); 34.7% very good partial responses (VGPR); and 21.9% partial responses (PR). Among triplet regimens, VMP was the most effective regimen compared to VCd, BDd, and VTd. Median PFS was 22.3 vs. 18.5 vs. 13.7 vs. 13.8 mo, (P = .275), respectively, and median OS was 49 vs. 41.7 vs. 37.9 vs. 32.2 mo (P = .004), respectively. The most common grade 3-4 toxicities were anemia in 17.4% and infections in 18% of patients. CONCLUSION: Our study confirmed that bortezomib-based treatment is effective and safe in NDMM transplant ineligible patients, especially VMP, which was identified as superior between bortezomib-based induction regimens not only in clinical trials, but also in real clinical practice.
- Klíčová slova
- bortezomib, multiple myeloma, patient, treatment,
- MeSH
- bortezomib terapeutické užití MeSH
- cyklofosfamid terapeutické užití MeSH
- dexamethason terapeutické užití MeSH
- doxorubicin terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- melfalan terapeutické užití MeSH
- mnohočetný myelom diagnóza farmakoterapie mortalita patologie MeSH
- prednison terapeutické užití MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- registrace * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- thalidomid terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- bortezomib MeSH
- cyklofosfamid MeSH
- dexamethason MeSH
- doxorubicin MeSH
- melfalan MeSH
- prednison MeSH
- thalidomid MeSH
Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov).
Lay abstract Proteasome inhibitors are drugs used in multiple myeloma (MM), a blood cancer that develops from cells in the bone marrow. Ixazomib is the first oral proteasome inhibitor to be approved for use in MM, when given in combination with two other oral drugs, lenalidomide and dexamethasone, to adult patients who have received one prior therapy. Our study, which was conducted in routine clinical practice, found that the effectiveness and safety of ixazomib + lenalidomide + dexamethasone in previously treated MM patients were similar to those seen in the Phase III clinical trial on which approval was based. These findings are important because they suggest that MM patients in everyday practice can achieve the same benefits from this treatment as patients in clinical trials, despite often being in poorer health.
- Klíčová slova
- effectiveness, ixazomib, multiple myeloma, proteasome inhibitor, relapsed/refractory, routine clinical practice,
- MeSH
- chemorezistence MeSH
- dexamethason aplikace a dávkování škodlivé účinky MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- glycin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- lenalidomid aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie mortalita MeSH
- mnohočetný myelom farmakoterapie mortalita patologie MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sloučeniny boru aplikace a dávkování škodlivé účinky 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
- multicentrická studie MeSH
- pozorovací studie MeSH
- Názvy látek
- dexamethason MeSH
- glycin MeSH
- ixazomib MeSH Prohlížeč
- lenalidomid MeSH
- sloučeniny boru MeSH
Despite the high efficacy of current induction regimens, most multiple myeloma (MM) patients relapse over time. The link between changes in the immune system and the prognosis of the disease is still not entirely clear. Therefore, we analyzed whether the pattern of bone marrow (BM) lymphocytes during routine BM examination after autologous stem cell transplant (ASCT) is related to disease prognosis or MRD negative complete remission. From 2009 to 2018, 98 MM patients underwent routine BM testing after the first ASCT. Using multi-parametric flow cytometry, twelve BM lymphocyte subtypes were analyzed. In 60% of patients who achieved a complete response (CR), MRD by flow cytometric analysis (sensitivity threshold 10-6) was evaluated. We found an association of relative proportion of BM lymphocyte subtypes with treatment response, progression-free survival (PFS), overall survival (OS), and minimal residual disease (MRD) negativity. Higher relative proportion of memory B cells was associated with inferior median PFS [HR 1.089 (95% CI: 1.023-1.160), p=0.008] and median OS [HR 1.170 (95% CI: 1.074-1.274), p<0.001]. In non-responding patients (minimal response and worse), higher proportion of memory B cells was found when compared to patients achieving CR [3.8% (range 0.5-35.0) vs. 1.0% (range 0.1-12.5); p=0.001]. No significant association of BM lymphocyte subtypes proportion with MRD negative CR was found. Our results show that changes in BM lymphocyte subsets including memory B cells may have prognostic value in MM patients after ASCT.
- MeSH
- autologní štěp MeSH
- autologní transplantace MeSH
- indukce remise MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- lymfocyty MeSH
- mnohočetný myelom * terapie MeSH
- prognóza MeSH
- reziduální nádor MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- amyloidóza * diagnóza genetika MeSH
- lehké řetězce imunoglobulinů genetika MeSH
- lidé MeSH
- molekulární patologie MeSH
- mutace MeSH
- plazmatické buňky MeSH
- primární amyloidóza * diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Názvy látek
- lehké řetězce imunoglobulinů MeSH
