Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Hemato
Special Issues
Waldenström Macroglobulinaemia and Related Conditions
share announcement

Waldenström Macroglobulinaemia and Related Conditions

A special issue of Hemato (ISSN 2673-6357). This special issue belongs to the section "Plasma Cell Disorders".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 35217

Special Issue Editors

Dr. Shirley D’Sa

E-Mail Website
Guest Editor
Cancer Division, University College London Hospitals NHS Foundation Trust, London, UK
Interests: waldenström macroglobulinaemia; real-world evidence; BTK inhibitors; Bing-Neel syndrome; IgM-related peripheral neuropathy; complement inhibition in cold agglutinin disease
Dr. Roger Owen

E-Mail Website
Guest Editor
Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, UK
Interests: waldenstrom macroglobulinaemia; myeloma; plasmacytoma; haematopathology; minimal residual disease
Dr. Dipti Talaulikar

E-Mail Website
Guest Editor
College of Health and Medicine, Australian National University, Canberra, Australia
Interests: non-Hodgkin lymphoma; waldenström macroglobulinaemia; marginal zone lymphoma; diffuse large B cell lymphoma; bruton's tyrosine kinase inhibitors; Bing-Neel syndrome; genomics; medical education
Dr. Josephine M.I. Vos

E-Mail Website
Guest Editor
Department of Hematology & Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Interests: non-Hodgkin lymphoma; waldenström macroglobulinaemia; marginal zone lymphoma; MGUS; monoclonal gammopathy of renal significance; IgM related peripheral neuropathy; auto-immune hemolytic anemia; cold agglutinin disease; Al amyloidosis; cryoglobulinemia

Special Issue Information

Dear Colleagues,

This Special Issue aims to provide a range of important clinical entities that affect patients with Waldenström Macroglobulinaemia (WM) and related conditions. It comes at a time of great change—hot on the heels of enormous biological and clinical developments in the monoclonal IgM field in the past 10 years and tempered by the advent of the COVID-19 global pandemic, which continues to have an impact on clinical practice.

The clinical features of WM and a spectrum of related conditions will be presented. The molecular landscape will be discussed along with its impact on disease behaviour and treatment response. The choice and impact of therapies is particularly important with the option of targeted therapies also available.

Entities of special interest will be discussed, including Bing-Neel syndrome and IgM-related neuropathies, cryoglobulinaemia and IgM-associated AL amyloidosis. The impact of COVID-19 will be addressed and how this influences clinical management of these conditions. Real-world evidence and patient experience are crucial aspects of managing conditions such as WM, which help us shape treatment algorithms. Such information is also highly valued by commissioning bodies as they appraise novel therapies, which are frequently costly, especially given the open-ended and continuous nature of many of these therapies.

Dr. Shirley D’Sa
Dr. Roger Owen
Dr. Dipti Talaulikar
Dr. Josephine M.I. Vos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Hemato is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • waldenström macroglobulinaemia
  • molecular landscape
  • immunochemotherapy
  • BTK inhibitors and other targeted therapies
  • cryoglobulinaemia
  • AL amyloidosis
  • Bing-Neel syndrome
  • IgM-related neuropathies
  • patient preferences
  • quality of life
  • COVID-19

Published Papers (10 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

11 pages, 264 KiB  
Article
IgM-Related Immunoglobulin Light Chain (AL) Amyloidosis
by Shayna Sarosiek, Andrew R. Branagan, Steven P. Treon and Jorge J. Castillo
Hemato 2022, 3(4), 731-741; https://doi.org/10.3390/hemato3040049 - 15 Nov 2022
Viewed by 2806
Abstract
Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic disorder characterized by an IgM paraprotein. The clinical presentation of WM varies and can include common manifestations such as anemia and hyperviscosity, in addition to less common features such as cryoglobulinemia, IgM-related neuropathy, and immunoglobulin light [...] Read more.
Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic disorder characterized by an IgM paraprotein. The clinical presentation of WM varies and can include common manifestations such as anemia and hyperviscosity, in addition to less common features such as cryoglobulinemia, IgM-related neuropathy, and immunoglobulin light chain (AL) amyloidosis. Amyloidosis is a protein-folding disorder in which vital organ damage occurs due to the accumulation of misfolded protein aggregates. The most common type of amyloidosis in patients with an IgM paraprotein is AL amyloidosis, although other types of amyloidosis may occur. IgM-related amyloidosis has distinct clinical features when compared with other subtypes of AL amyloidosis. This review highlights the diagnostic criteria of IgM-related AL amyloidosis, as well as the clinical characteristics and treatment options for this disorder. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)

Review

Jump to: Research

14 pages, 911 KiB  
Review
MYD88 Wild Type in IgM Monoclonal Gammopathies: From Molecular Mechanisms to Clinical Challenges
by Tina Bagratuni, Alexandra Papadimou, Kostantina Taouxi, Meletios A. Dimopoulos and Efstathios Kastritis
Hemato 2023, 4(3), 259-272; https://doi.org/10.3390/hemato4030021 - 13 Sep 2023
Viewed by 1201
Abstract
High frequencies of MYD88L265P mutation are observed in IgM monoclonal gammopathies, and specifically in Waldenström macroglobulinemia (WM), indicating this mutation as a potential disease biomarker. Given the fact that MYD88L265P mutation has been described as a key driver mutation, has increased [...] Read more.
High frequencies of MYD88L265P mutation are observed in IgM monoclonal gammopathies, and specifically in Waldenström macroglobulinemia (WM), indicating this mutation as a potential disease biomarker. Given the fact that MYD88L265P mutation has been described as a key driver mutation, has increased our understanding of the biology behind MYD88 signaling and helped us to identify the functional components which could be targeted. On the other hand, the absence of the MYD88L265P mutation in patients with IgM monoclonal gammopathies has been associated with a higher risk of transformation to aggressive lymphomas, resistance to several therapies, and shorter overall survival. The present review focuses on the molecular mechanisms that shape the signaling pattern in MYD88WT cells, as well as on the clinical implications and therapeutic challenges of WM patients that harbor the MYD88WT genotype. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

12 pages, 667 KiB  
Review
Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders
by Guy Pratt, Hannah V. Giles and Jennifer H. Pinney
Hemato 2023, 4(2), 184-195; https://doi.org/10.3390/hemato4020015 - 14 Jun 2023
Viewed by 1717
Abstract
Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies [...] Read more.
Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies associated with WM and IgM MGUS than that seen in patients with multiple myeloma, where cast nephropathy predominates. In WM, uncommonly direct infiltration of the renal system by lymphoma or cast nephropathy with a high light-chain level can occur. AL amyloidosis can present with nephrotic syndrome as a feature with IgM MGUS or WM. Cryoglobulinaemia and light-chain deposition disease are other important potential causes of renal impairment with IgM MGUS and WM. There are other rarer monoclonal gammopathy of renal significance (MGRS) conditions characterised by typically isolated kidney disease that are causally related to a B-cell or plasma-cell clonal disorder usually in a precancerous MGUS state, although in some renal pathologies, the association is less clear. Central to the majority of these diagnoses is the need for an accurate renal histological diagnosis, and management requires close joint working of renal and haematology teams. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

23 pages, 1700 KiB  
Review
BTK Inhibitors and Other Targeted Therapies in Waldenström Macroglobulinemia
by Karan L. Chohan and Prashant Kapoor
Hemato 2023, 4(2), 135-157; https://doi.org/10.3390/hemato4020012 - 13 Apr 2023
Cited by 1 | Viewed by 2762
Abstract
Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel “druggable” [...] Read more.
Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel “druggable” targets that have been identified within the clonal lymphoplasmacytic cells in WM have resulted in a rapid development of targeted therapies in both the frontline and relapsed and refractory (R/R) settings. Several agents directed against the known targets have shown promising efficacy, with mostly manageable toxicities. The class of Bruton’s tyrosine kinase (BTK) inhibitors has transformed the therapeutic landscape for patients with WM, given their convenient oral dosing and strong efficacy, with high rates of attainment of very good partial response (VGPR). The tolerability of the next-generation BTK inhibitors appears to be superior to that of the first-in-class agent, ibrutinib. Targeted therapies from other classes have also demonstrated efficacy in both single-agent and combination regimens. Inhibitors of proteasome BCL-2, mTOR and PI-3 kinase have demonstrated efficacy in WM. Emerging therapies under investigation will continue to further shape the management paradigm, especially in the R/R setting. These include bispecific antibodies, radiotherapeutic agents and chimeric antigen receptor T-cell (CART) cell therapies. This review outlines the current literature and future direction of targeted therapies in WM. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

13 pages, 1061 KiB  
Review
Bing–Neel Syndrome: Update on Diagnosis and Treatment
by Evangeline Y. Wong, Shirley D’Sa, Monique C. Minnema, Jorge J. Castillo and Dipti Talaulikar
Hemato 2022, 3(4), 758-770; https://doi.org/10.3390/hemato3040051 - 29 Nov 2022
Viewed by 6793
Abstract
Bing–Neel syndrome (BNS) is a rare neurological complication of Waldenström macroglobulinaemia. We highlight key issues in clinical presentation, diagnosis, and treatment while focusing on new and emerging therapies available for patients diagnosed with BNS. It is anticipated that further development of Bruton Tyrosine [...] Read more.
Bing–Neel syndrome (BNS) is a rare neurological complication of Waldenström macroglobulinaemia. We highlight key issues in clinical presentation, diagnosis, and treatment while focusing on new and emerging therapies available for patients diagnosed with BNS. It is anticipated that further development of Bruton Tyrosine Kinase (BTK) inhibitors and less toxic chemoimmunotherapies will improve treatment delivery and response. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

14 pages, 305 KiB  
Review
First-Line Treatment of Waldenström’s Macroglobulinaemia: Considerations Based on the Dutch National Guideline
by Karima Amaador, Marie José Kersten, Hein P. J. Visser, Laurens Nieuwenhuizen, Roelandt F. J. Schop, Martine E. D. Chamuleau, Gerjo A. Velders, Monique C. Minnema and Josephine Mathilde Iris Vos
Hemato 2022, 3(4), 704-717; https://doi.org/10.3390/hemato3040047 - 26 Oct 2022
Viewed by 2516
Abstract
Waldenström macroglobulinemia (WM) is a rare B-cell Non-Hodgkin Lymphoma. There are only few prospective randomized clinical trials to guide treatment recommendations and there is no international consensus on a preferred first line treatment approach. In the recently revised Dutch guideline for WM, we [...] Read more.
Waldenström macroglobulinemia (WM) is a rare B-cell Non-Hodgkin Lymphoma. There are only few prospective randomized clinical trials to guide treatment recommendations and there is no international consensus on a preferred first line treatment approach. In the recently revised Dutch guideline for WM, we describe recommendations for practice based as much as possible on the known data. Here, we summarize the considerations for first-line treatment based on these Dutch guidelines. Available evidence is summarized, including efficacy and toxicity data. Combinations of Rituximab with chemotherapy, proteasome inhibition or BTK-inhibition are all valid first line treatment options. The Dutch WM working group considers Dexamethasone/Rituximab/Cylofosfamide (DRC) a suitable first-line treatment for many WM patients, given the efficacy, the relatively mild toxicity profile and the extensive experience with this regimen. However, the long-term toxicities of DRC are unclear and need further clarification. Other regimens such as R-bendamustine, R-Bortezomib-dexamethason are also effective options, however with specific toxicities. BTK-inhibitors are not a preferred option in first line for most patients in the Dutch WM guidelines because of the need for longterm treatment and toxicities. Based on patient preferences research, future clinical trials should focus on effective fixed-duration regimens with non-cytotoxic therapies that have a favorable toxicity profile. Further development of (combinations with) BCL-2 inhibititors, novel proteasome inhibitors and BTK-inhibition could be interesting. In addition T-cell-directed treatments including bispecific antibodies as a monotherapy or combined with other novel agents deserve further study in WM. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
15 pages, 576 KiB  
Review
Should Patients with Waldenström Macroglobulinemia Receive a BTK Inhibitor as Frontline Therapy?
by Marina Deodato, Anna Maria Frustaci, Giulia Zamprogna, Giulia Cotilli, Roberto Cairoli and Alessandra Tedeschi
Hemato 2022, 3(4), 689-703; https://doi.org/10.3390/hemato3040046 - 23 Oct 2022
Viewed by 1988
Abstract
Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma with heterogeneous clinical presentation. As there are no randomised trials suggesting the best treatment option in treatment-naive patients, guidelines suggest either rituximab-combining regimens or BTK-inhibitors (BTKi) as feasible alternatives. Several factors play in the decision-making [...] Read more.
Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma with heterogeneous clinical presentation. As there are no randomised trials suggesting the best treatment option in treatment-naive patients, guidelines suggest either rituximab-combining regimens or BTK-inhibitors (BTKi) as feasible alternatives. Several factors play in the decision-making process: patients’ age and fitness, disease characteristics and genotype. Chemoimmunotherapy (CIT) represents a fixed-duration, less expensive and effective option, able to achieve prolonged time-to-next treatment even in patients with unfavourable genotypes. Immunosuppression and treatment-related second cancers may represent serious concerns. Proteasome-inhibitor-based regimens are effective with rapid disease control, although bortezomib-related neuropathy discourages the choice of these agents and treatment schedules may not be easily manageable in the elderly. BTKi have demonstrated high rates of response and prolonged survival together with the convenience of an oral administration and limited cytopenias. However, outcomes are impacted by genotype and some concerns remain, in particular the continuous drug exposure that may result in extra-haematological complications and drug resistance. Although next-generation BTKi have improved treatment tolerance, the question whether BTKi should be offered as frontline therapy to every patient is still debated. Giving fixed-duration schedule, prolonged time-to-next treatment and outcomes independent of genotype, CIT is still our preferred choice in WM. However, BTKi remain a valuable option in frail patients unsuitable for CIT. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

26 pages, 768 KiB  
Review
Polyneuropathy Associated with IgM Monoclonal Gammopathy; Advances in Genetics and Treatment, Focusing on Anti-MAG Antibodies
by Johannes P. M. van de Mortel, Shirley D’Sa, Alexander F. J. E. Vrancken, Nicolette C. Notermans, Josephine M. I. Vos and Monique C. Minnema
Hemato 2022, 3(4), 663-688; https://doi.org/10.3390/hemato3040045 - 17 Oct 2022
Cited by 1 | Viewed by 4832
Abstract
With increasing age, the chances of developing either MGUS or polyneuropathy increase as well. In some cases, there is a causative relationship between the IgM M-protein and polyneuropathy. In approximately half of these cases, IgM targets the myelin-associated glycoprotein (MAG). This results in [...] Read more.
With increasing age, the chances of developing either MGUS or polyneuropathy increase as well. In some cases, there is a causative relationship between the IgM M-protein and polyneuropathy. In approximately half of these cases, IgM targets the myelin-associated glycoprotein (MAG). This results in chronic polyneuropathy with slowly progressive, predominantly sensory neurological deficits and distally demyelinating features in nerve conduction studies. Despite the disease being chronic and developing slowly, it can cause considerable impairment. We reviewed English medical publications between 1980 and May 2022 on IgM gammopathy-associated polyneuropathy, with special attention to studies addressing the pathophysiology or treatment of anti-MAG polyneuropathy. Treatment options have been limited to a temporizing effect of intravenous immunoglobulins in some patients and a more sustained effect of rituximab but in only 30 to 55 percent of patients. An increase in our knowledge concerning genetic mutations, particularly the MYD88L265P mutation, led to the development of novel targeted treatment options such as BTK inhibitors. Similarly, due to the increasing knowledge of the pathophysiology of anti-MAG polyneuropathy, new treatment options are emerging. Since anti-MAG polyneuropathy is a rare disease with diverse symptomatology, large trials with good outcome measures are a challenge. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

13 pages, 1163 KiB  
Review
Transformed Waldenström Macroglobulinemia: Update on Diagnosis, Prognosis and Treatment
by Eric Durot, Cécile Tomowiak, Elise Toussaint, Pierre Morel, Dipti Talaulikar, Prashant Kapoor, Jorge J. Castillo and Alain Delmer
Hemato 2022, 3(4), 650-662; https://doi.org/10.3390/hemato3040044 - 12 Oct 2022
Cited by 1 | Viewed by 2633
Abstract
Histological transformation (HT) to an aggressive lymphoma results from a rare evolution of Waldenström macroglobulinemia (WM). A higher incidence of transformation events has been reported in MYD88 wild-type WM patients. HT in WM can be histologically heterogeneous, although the diffuse large B-cell lymphoma [...] Read more.
Histological transformation (HT) to an aggressive lymphoma results from a rare evolution of Waldenström macroglobulinemia (WM). A higher incidence of transformation events has been reported in MYD88 wild-type WM patients. HT in WM can be histologically heterogeneous, although the diffuse large B-cell lymphoma of activated B-cell subtype is the predominant pathologic entity. The pathophysiology of HT is largely unknown. The clinical suspicion of HT is based on physical deterioration and the rapid enlargement of the lymph nodes in WM patients. Most transformed WM patients present with elevated serum lactate dehydrogenase (LDH) and extranodal disease. A histologic confirmation regarding the transformation to a higher-grade lymphoma is mandatory for the diagnosis of HT, and the choice of the biopsy site may be dictated by the findings of the 18fluorodeoxyglucose-positron emission tomography/computed tomography. The prognosis of HT in WM is unfavorable, with a significantly inferior outcome compared to WM patients without HT. A validated prognostic score based on 3 adverse risk factors (elevated LDH, platelet count < 100 × 109/L and any previous treatment for WM) stratifies patients into 3 risk groups. The most common initial treatment used is a chemo-immunotherapy (CIT), such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). The response duration is short and central nervous system relapses are frequent. Whether autologous stem cell transplantation could benefit fit patients responding to CIT remains to be studied. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

21 pages, 2770 KiB  
Review
Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy
by Sigbjørn Berentsen, Shirley D’Sa, Ulla Randen, Agnieszka Małecka and Josephine M. I. Vos
Hemato 2022, 3(4), 574-594; https://doi.org/10.3390/hemato3040040 - 20 Sep 2022
Cited by 6 | Viewed by 6568
Abstract
The last 2 decades have seen great progress in understanding the pathogenesis of cold agglutinin disease (CAD) and development of effective therapies. Cold agglutinins can cause hemolytic anemia as well as peripheral circulatory symptoms such as acrocyanosis. We distinguish CAD, a well-defined clinicopathologic [...] Read more.
The last 2 decades have seen great progress in understanding the pathogenesis of cold agglutinin disease (CAD) and development of effective therapies. Cold agglutinins can cause hemolytic anemia as well as peripheral circulatory symptoms such as acrocyanosis. We distinguish CAD, a well-defined clinicopathologic entity, from secondary cold agglutinin syndrome. This review addresses the histopathologic, immune phenotypic, and molecular features that allow CAD to be classified as a distinct clonal lymphoproliferative disorder of the bone marrow, recently recognized in the WHO classification. We discuss recent data on the possible overlap or distinction between CAD and Waldenström’s macroglobulinemia. Two major steps in the pathogenesis of CAD are identified: clonal B-cell lymphoproliferation (leading to monoclonal IgM production) and complement-mediated hemolysis. Each of these steps constitutes a target for treatment. Established as well as novel and experimental therapies are reviewed. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-10
Back to TopTop