SOHO State of the Art Updates and Next Questions: Waldenström Macroglobulinemia - 2021 Update on Management and Future Directions

Thomas, Sheeba K.

doi:10.1016/j.clml.2021.11.014

Cited by 7 publications

(7 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, Waldenstr€ om macroglobulinemia (WM) is an incurable, indolent, IgM-secreting lymphoplasmacytic lymphoma (LPL), involving somatic mutations in the gene encoding the adaptor protein MYD88 (point mutations) in >90% of cases and mutations in the CXCR4 (frameshift or nonsense mutations, including known WHIM mutations) in $30% of patients. The disease is characterized by infiltration of LPL in the bone marrow, as well as IgM monoclonal gammopathy (48). A risk factor for developing WM and LPL-WM is septicemia with odds ratios of 2.6 and 2.4, respectively.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Hematologic Effects of Endotoxin in Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome Model Mice

et al. 2022

View full text Add to dashboard Cite

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function CXCR4 mutations that promote severe panleukopenia caused by bone marrow retention of mature leukocytes. Consequently, WHIM patients develop recurrent bacterial infections; however, sepsis is uncommon. To study this clinical dichotomy, we challenged WHIM model mice with LPS. The LD 50 was similar in WHIM and wild-type (WT) mice, and LPS induced acute lymphopenia in WT mice that was Cxcr4 independent. In contrast, in WHIM mice, LPS did not affect circulating T cell levels, but the B cell levels anomalously increased because of selective, cell-intrinsic, and Cxcr4 WHIM allele-dependent emergence of Cxcr4 high late pre-B cells, a pattern that was phenocopied by Escherichia coli infection. In both WT and WHIM mice, the CXCR4 antagonist AMD3100 rapidly increased circulating lymphocyte levels that then rapidly contracted after subsequent LPS treatment. Thus, LPS-induced lymphopenia is CXCR4 independent, and a WHIM mutation does not increase clinical LPS sensitivity. Anomalous WT Cxcr4-independent, but Cxcr4 WHIM-dependent, promobilizing effects of LPS on late pre-B cell mobilization reveal a distinct signaling pathway for the variant receptor.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical and Hematologic Effects of Endotoxin in Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome Model Mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Black patients less commonly have IgM monoclonal gammopathy compared with white patients. Median age at diagnosis is 63 years for blacks and 73 for whites, with blacks having a shorter survival than whites 8 …”

Section: Disease Overviewmentioning

confidence: 99%

“…Median age at diagnosis is 63 years for blacks and 73 for whites, with blacks having a shorter survival than whites. 8 Survival of WM is improving. The SEER database contained 5784 patients with WM.…”

Section: Disease Overviewmentioning

confidence: 99%

Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management

Gertz

2023

American J Hematol

View full text Add to dashboard Cite

Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity.Diagnosis: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis.Risk Stratification: Age, hemoglobin level, platelet count, β 2 microglobulin, LDH, and monoclonal IgM concentrations are characteristics that are predictive of outcomes.Risk-Adapted Therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or a BTK inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib. Management of RefractoryDisease: Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection. 1 | PATIENT A 55-year-old male was found to have an IgM monoclonal gammopathy in January 2005. He was observed until November 2010 when his IgM level climbed to 9135 mg/dl. He was treated with rituximab, bortezomib, and dexamethasone for 4 months. Treatment was interrupted due to neuropathy, but the IgM level fell to 1150. He was observed until April 2015. At the time of progression his IgM was 11 500 mg/dl and he was found to have acquired von Willebrand disease. 1 He was treated with single-agent rituximab which failed to produce a minor response. He received bendamustine, lenalidomide, and rituximab with a response of <1 year. In 2018 he was placed on an experimental trial of oprozomib with a response of 5 years duration. At relapse in August of 2022, he was placed on a trial of ixazomib and ibrutinib. Ixazomib was poorly tolerated due to diarrhea, and he continued ibrutinib alone and has achieved a very good partial response.

show abstract

“…Mutations of the MYD88 gene are detected in 93% to 97% of patients with Waldenström macroglobulinemia. Other symptoms or signs of the disease can include hemoglobin of less than 10 g/dL, platelet count of less than 100 × 10 9 /L, bulky adenopathy or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, secondary amyloidosis, or cryoglobulinemia 61 …”

Section: Waldenström Macroglobulinemiamentioning

confidence: 99%

Hematologic Disorders and the Nervous System

Mauermann¹,

Southerland²

2023

CONTINUUM: Lifelong Learning in Neurology

View full text Add to dashboard Cite

OBJECTIVE This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of red blood cell, platelet, and plasma cell disorders. LATEST DEVELOPMENTS Cerebrovascular complications can occur in patients with blood cell and platelet disorders. Treatment strategies to prevent stroke are available for patients with sickle cell disease, polycythemia vera, and essential thrombocythemia. A diagnosis of thrombotic thrombocytopenic purpura should be considered in patients with neurologic symptoms, hemolytic anemia, thrombocytopenia, mild renal insufficiency, and fever. Plasma cell disorders can be associated with peripheral neuropathy, and classification of the monoclonal protein type and neuropathy aid in diagnosis. Patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome can present with arterial and venous neurologic events. ESSENTIAL POINTS This article discusses the neurologic complications of blood cell disorders and the most recent advances in prevention and treatment.

show abstract

SOHO State of the Art Updates and Next Questions: Waldenström Macroglobulinemia - 2021 Update on Management and Future Directions

Cited by 7 publications

References 72 publications

Clinical and Hematologic Effects of Endotoxin in Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome Model Mice

Clinical and Hematologic Effects of Endotoxin in Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome Model Mice

Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management

Hematologic Disorders and the Nervous System

Contact Info

Product

Resources

About