The diagnosis of Waldenström's macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström's Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests, and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.
- MeSH
- hybridizace in situ fluorescenční MeSH
- imunoglobulin M MeSH
- lidé MeSH
- Waldenströmova makroglobulinemie * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.
- MeSH
- bendamustin hydrochlorid MeSH
- folikulární lymfom * patologie MeSH
- lidé MeSH
- neutropenie * chemicky indukované MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- rituximab MeSH
- trombocytopenie * etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- multicentrická studie MeSH
PURPOSE: Rituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM. METHODS: In this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety. RESULTS: Two hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC (P = .32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P < .01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade ≥ 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC. CONCLUSION: This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.
- MeSH
- bortezomib škodlivé účinky MeSH
- cyklofosfamid MeSH
- dexamethason MeSH
- lidé MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- rituximab MeSH
- Waldenströmova makroglobulinemie * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Background: Infectious complications, especially febrile neutropenia, in hemato-oncological patients are associated with considerable morbidity, mortality and expenses. Remote monitoring of physiological functions and thus early detection of adverse events via telemedicine could improve the safety of these high-risk patients and save financial resources by shortening the time-to-antibiotics. Methods: Patients undergoing active cancer treatment in high risk of acquiring severe infection are selected and enrolled in this project. Each patient receives a digital blood pressure monitor, an infrared thermometer and a mobile hub (cell phone). In the comfort of their homes, patients measure their blood pressure/pulse and body temperature regularly or whenever they feel unwell. The obtained data are encrypted and forwarded via the mobile hub to the password-protected portal. The values registered outside the set-up range trigger the alarms, which are immediately sent to the designated physician who can check the portal in real-time from any device with an Internet connection, contact the patient, if need be, and initiate the anti-infective therapy almost instantly after the first symptoms occur. Results: Fifty hemato-oncological patients were recruited between March 1, 2018 and August 1, 2020. Two hundred ninety-seven alarms of body temperature were registered and checked by the physician and patients were contacted in 18.5% of the cases (55/297). Among these 55 events, 13 required medical assistance, which makes it approximately one-quarter of all conducted telephone interventions (23.4%) and neither septic shock nor death due to treatment-related toxicity occurred. Conclusion: Telemedicine seems like a useful tool to improve the safety of high risk hemato-oncological patients when treatment-related infectious complications are concerned.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy. PATIENTS AND METHODS: We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m). RESULTS: Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy. CONCLUSION: Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.
- MeSH
- adjuvantní chemoterapie MeSH
- antitumorózní látky alkylující aplikace a dávkování škodlivé účinky MeSH
- autologní transplantace MeSH
- časové faktory MeSH
- chemoterapie konsolidační MeSH
- doba přežití bez progrese choroby MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lenalidomid aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom diagnóza mortalita terapie MeSH
- multicentrické studie jako téma MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- reziduální nádor MeSH
- rizikové faktory MeSH
- transplantace kmenových buněk * škodlivé účinky mortalita MeSH
- udržovací chemoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Aldehyde dehydrogenase (ALDH) is highly active in physiological stem cells as well as in tumor-initiating cells of some malignancies including multiple myeloma (MM). Finding higher activity of ALDH in some cell subsets in monoclonal gammopathies (MG) could identify potential source of myeloma-initiating cells (MICs). METHODS: Bone marrow of 12 MM, 9 monoclonal gammopathy of undetermined significance (MGUS), and 10 healthy donors (HD) were analyzed by flow cytometry. ALDH activity of B-cells and plasma cells (PC) was analyzed using Aldefluor. RESULTS: Similar changes of ALDH activity were found during B-cell development in HD and MG. Decreasing of ALDH activity from immature to naïve B-cells was found. In postgerminal stages, the activity started to increase, and in PCs, the ALDH activity was the same as in immature B-cells. Increased ALDH activity of all PC subsets compared to naïve B-cells was found in MM as well as in HD, while in MGUS, only CD19(-) PCs have higher ALDH activity. In HD, ALDH activity was higher in CD19(+) PCs compared with MG. CONCLUSIONS: Our results indicate that changes of ALDH activity are the natural phenomenon in B-cell development; thus, high ALDH activity as a single marker is not appropriate for MICs identification.
- MeSH
- aktivace enzymů MeSH
- aldehyddehydrogenasa metabolismus MeSH
- antigeny povrchové metabolismus MeSH
- B-lymfocyty enzymologie patologie MeSH
- biologické markery MeSH
- dospělí MeSH
- imunofenotypizace MeSH
- kostní dřeň patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom diagnóza enzymologie MeSH
- monoklonální gamapatie nejasného významu diagnóza enzymologie MeSH
- paraproteinemie diagnóza enzymologie MeSH
- plazmatické buňky enzymologie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- studie případů a kontrol 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
