The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis). There is an expanding array of treatment options, but high-quality data are sparse. Diagnostic accuracy is important and needs collaboration between hematologists and neuromuscular specialists to determine the sequence and intensity of investigations. Appropriate causal attribution to the IgM disorder is essential to enable the correct therapeutic intervention. The aims of treatment intervention should be clear and realistic. Consistent and clinically meaningful measures are needed to capture treatment success. Despite therapeutic advances, many patients experience persistent disability, highlighting the need for further research.
- MeSH
- imunoglobulin M * imunologie MeSH
- lidé MeSH
- management nemoci MeSH
- nemoci periferního nervového systému * terapie diagnóza etiologie imunologie MeSH
- Waldenströmova makroglobulinemie * terapie komplikace diagnóza imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
The Consensus Panel 3 (CP3) of the 12th International Workshop on Waldenström macroglobulinemia (IWWM-12) has reviewed and incorporated current data to make recommendations for the management of patients with high-risk WM (HR-WM). Recognizing the considerable heterogeneity in survival outcomes and identifying a subgroup of patients with a very poor prognosis, the key recommendations from CP3 include: (1) Risk stratifying patients with smoldering WM (SWM) and active (symptomatic) WM at diagnosis (2) Using the degree of i) bone marrow lymphoplasmacytosis, ii) serum beta-2 microglobulin (β2M) elevation, iii) IgM increase, iv) serum albumin decrease and the presence of wild-type MYD88 status markers that adversely dictate the time-to-progression from smoldering to active WM to the define HR-SWM. (3) Among patients with active WM, the presenting parameters: advanced chronological age, low serum albumin, elevated serum lactate dehydrogenase, elevated β2M and the presence of TP53 alterations (TP53 mutation or deletion 17p) unfavorably impact the prognosis and should be utilized to risk-stratify patients into the HR category. (4) The panel encourages screening for genetic alterations at diagnosis, prior to initiating therapy and also with rapidly advancing disease or refractoriness to ongoing therapy, which might result from clonal evolution. Although limited data directing the selection and sequencing of therapies exist, a risk-adapted approach and clinical trial participation for patients with HR-WM are highly encouraged.
- MeSH
- beta-2-mikroglobulin krev MeSH
- konsensus MeSH
- lidé MeSH
- management nemoci MeSH
- prognóza MeSH
- Waldenströmova makroglobulinemie * terapie diagnóza genetika krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
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
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 protinádorové 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
Editio altera ab innvmeris mendis repvrgata et praeclaris locvpletata accessionibvs [24], 728, [23], 103, [5] s. : frontispis, il. ; 21 cm
Editio altera ab innvmeris mendis repvrgata et praeclaris locvpletata accessionibvs [24], 728, [23], 103, [5] stran : frontispis, ilustrace ; 21 cm
[19], 296 s. : 15 cm
- MeSH
- lékařství MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- lékařství
