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
BACKGROUND: Plasmacytoid dendritic cells (pDCs) play prominent roles in mediating innate and adaptive immune responses. However, it is unclear how pDCs contribute to the immunosuppressive tumor microenvironment described in multiple myeloma (MM). METHODS: Newly diagnosed myeloma patients (MM, n = 37) were analyzed to determine the pDC counts in comparison to peripheral blood (PB, n = 53) and bone marrow (BM, n = 10) samples of age-matched healthy donors (HD) using flow cytometry. Second, proliferation of myeloma tumor cells in the presence of freshly isolated pDCs was examined. Third, production of IFNα by pDCs co-cultured with MM cells was determined by intracellular staining. RESULTS: We found a highly significant reduction of circulating pDCs (p < 0.0001) and in bone marrow (p < 0.0001) of MM patients compared to HD. We also observed a significant decrease of pDCs (p = 0.004) in BM in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 12). Importantly, we determined that pDCs promote proliferation specifically of MM cells and not the stromal cells and that pDCs secrete IFNα upon co-culture with MM tumor cells. CONCLUSIONS: Our results show altered pDC frequencies in the BM microenvironment in MGUS and MM patients at diagnosis. We showed the tumor-promoting function of pDCs that may mediate immune deficiencies affecting long-term disease control and treatment outcome.
- Klíčová slova
- MGUS, immunosuppressive tumor microenvironment, multiple myeloma, plasmacytoid dendritic cells,
- Publikační typ
- časopisecké články 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
- lidé MeSH
- mnohočetný myelom * diagnóza terapie MeSH
- průtoková cytometrie MeSH
- referenční standardy MeSH
- reziduální nádor MeSH
- studie proveditelnosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
Heparin-induced thrombocytopenia (HIT) is an immunologically-mediated complication, which usually follows heparin exposition, less frequently exposition to other drugs or even occurs spontaneously. The type of heparin, its dose and mode of application as well as the exposition time, major trauma or operation, and obesity represent the main risk factors for HIT. The probability of HIT correlates with so-called 4T-score. A confirmatory laboratory diagnostic should be exclusively reserved for patients with a medium to a high probability of HIT development (more than 3 points in 4T-score). The screening method is based on serological detection of antibodies against heparin-platelet factor-4 complexes; confirmation tests aim to identify the activation of platelets. The treatment of HIT requires an immediate interruption of heparin application and rigorous antithrombotic treatment with an alternative agent. Herein authors describe a clinical case of HIT manifested as an extreme urticarial reaction in the location of nadroparin application as well as thrombosis of deep subcutaneous veins in a polymorbid obese patient with an extensive and infected burn. Due to timely diagnosis and fondaparinux treatment, no more severe thrombotic events occurred in this patient.
- Klíčová slova
- 4T-scores, direct oral anticoagulants, fondaparinux, heparin‑induced thrombocytopenia, thrombosis,
- MeSH
- antikoagulancia škodlivé účinky MeSH
- fondaparinux MeSH
- heparin škodlivé účinky MeSH
- lidé MeSH
- trombocytopenie * chemicky indukované diagnóza MeSH
- trombóza * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Názvy látek
- antikoagulancia MeSH
- fondaparinux MeSH
- heparin MeSH
