Waldenström macroglobulinemia (WM) is a B-cell lymphoma characterized by the presence of bone marrow lymphoplasmacytic infiltration and circulating monoclonal immunoglobulin M protein. The clinical presentation of WM is variable, ranging from gradually progressive cytopenias, organomegaly, fatigue, B symptoms, and peripheral neuropathy to the more emergent presentation with symptomatic hyperviscosity, cryoglobulinemia, hemolytic anemia-associated symptoms, acquired von Willebrand disease or acquired hemophilia-associated bleeding. Approximately 1 in 5 patients with WM are asymptomatic at diagnosis and classified as having smoldering WM, not requiring WM-directed therapy. Although WM typically has an indolent, relapsing-remitting course, the outcomes are heterogeneous. The prognosis of patients with WM is known to be impacted by certain clinical and laboratory features at initial presentation, with advanced age, elevated serum lactate dehydrogenase, and low serum albumin unfavorably affecting the outcome. Although complications such as histologic transformation or light and/or heavy chain (AL/ALH) amyloidosis are infrequent, their occurrence adversely influences the disease course. The International Prognostic Staging System for WM (IPSS-WM) is a validated model, often used in clinical practice, but needs to be reexamined in the current era. The discovery of the recurrent MYD88L265P gain-of-function point mutation and the subclonal CXCR4 mutations has helped improve our understanding of the WM biology, and the prognostic impact of these mutations is under evaluation, with somewhat inconsistent findings thus far across studies. This review discusses the clinical presentation, diagnostic criteria, and prognostic markers of WM.

Waldenström macroglobulinemia (WM) is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M (IgM) protein (Owen et al., 2003). Common signs and symptoms include fatigue due to anemia, lymph node enlargement, hepatosplenomegaly, thrombocytopenia, symptoms related to high viscosity, and peripheral neuropathy, among others. Despite significant advances in WM treatment, this type of indolent lymphoma remains incurable, with a wide array of patient outcomes (Ruan et al., 2020). In recent years, chimeric antigen receptor T (CAR-T) cell therapy targeting cluster of differentiation 19 (CD19) has shown unprecedented response rates and durability in the treatment of B-cell malignancies. In this report, we describe a challenging case of WM that involved multiple extramedullary sites, relapsed, and was refractory to chemotherapy, immunotherapy, and targeted therapy. After anti-CD19 CAR-T cell therapy, the tumor burden significantly decreased and the patient\'s condition remained stable at the writing of this report.
华氏巨球蛋白血症（WM）是一种罕见的小淋巴细胞、浆细胞样淋巴细胞和浆细胞肿瘤，会累及骨髓，甚至累及淋巴结和脾，通常与克隆性IgM球蛋白血症相关。尽管WM通常伴有惰性临床病程，但却无法治愈。本研究报告了一个具有挑战性的WM案例。该患者在化疗、免疫治疗和布鲁顿酪氨酸激酶（BTK）抑制剂治疗后出现复发/难治性病变，并累及髓外，但在CD19定向嵌合抗原受体T（CAR-T）细胞治疗后病情得到改善。此外，我们还回顾了文献中报道的CAR-T细胞治疗WM病例。本案例中的患者已接受一年多的随访，其病情仍保持良好的部分缓解状态，这表明CAR-T细胞疗法具有作为复发/难治性WM替代方案的潜力。人们迫切希望进行更大规模的临床研究来评估这种疗法的有效性和安全性。.

暂无摘要。

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.

BACKGROUND: Serum lipid profiles play a crucial role in diagnosing and evaluating cardiovascular diseases. However, the presence of paraprotein can lead to inaccurate dyslipidemia results on automated analyzers.
METHODS: A 65-year-old woman whose combined concentrations of HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) consistently surpassed her total serum cholesterol levels over a period of three months presented with unusual lipid component detection. Further analysis revealed the presence of a monoclonal paraprotein, identified as an IgMλ band, with a concentration of 28.0 g/L. The patient was subsequently diagnosed with Waldenström macroglobulinemia. The use of abnormal reaction kinetic curves and the β quantification method, along with an alternative method that did not suffer from interference, revealed that the monoclonal paraprotein interfered with the measurements of HDL-C, LDL-C, apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB) when using the Roche detection system. This interference led to spurious elevated HDL-C concentrations and falsely decreased apoA-I and apoB concentrations, while the LDL-C results were minimally affected. Although diluting the sample normalized the HDL-C and LDL-C measurements, the interference with the apoA-I and apoB assays persisted. No other common biochemical tests were interfered with this paraprotein.
CONCLUSIONS: Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable.

Paraneoplastic syndrome is a broad spectrum of signs and symptoms due to neoplasm, attributed to substances produced by tumor cells, or in response to it. Myasthenia gravis (MG) is a well-known paraneoplastic neurological syndrome (PNS), frequently associated with thymic abnormalities, but rarely reported in patients with lymphoplasmacytic lymphoma.This study presents the case of a 52-year-old Indonesian male patient who was diagnosed with Waldenstrom macroglobulinemia (WM), a rare B-cell neoplasm, after developing a new onset of MG with myasthenic crisis. the patient\'s MG features improved with Ibrutinib as a treatment targeted toward cancer. This is the first case report presenting the treatment response of Ibrutinib in WM with myasthenic crisis. The literature was reviewed to explain the possibility of MG as a paraneoplastic syndrome of WM and the treatment response of Ibrutinib for this patient, as well as summarizing previous case reports of concomitant MG and WM.MG should be considered a paraneoplastic malignancy syndrome, including WM, during diagnostic workup. Ibrutinib should also be considered when available to patients, due to its adequate response in both previously treated and treatment naïve patients.

OBJECTIVE: To evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients.
METHODS: Prospective study.
METHODS: A total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA RESULTS: The two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17% vs. 52.99 ± 2.52 %; p < 0.001), as well as in the parafovea (53.01 ± 6.69% vs. 55.30 ± 2.61 %; p = 0.002), and fovea (21.38 ± 9.01% vs. 30.31 ± 5.84 %; p < 0.0001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07% vs. 50.83 ± 5.46 %; p = 0.005), as well as in the parafovea (56.76 ± 6.26% vs. 52.59 ± 5.46 %; p = 0.0001), and fovea (38.75 ± 8.59% vs. 33.43 ± 8.68 %; p < 0.0001).
CONCLUSIONS: The finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.

OBJECTIVE: Waldenström macroglobulinemia is a rare non-Hodgkin lymphoma (NHL) characterized by lymphoplasmacytic bone marrow infiltration associated with an immunoglobulin M (IgM) monoclonal gammopathy. Over the past two decades, a number of important novel therapies have emerged for the treatment of relapsed and refractory (R/R) WM. The purpose of this review is to discuss these novel agents.
RESULTS: Chemoimmunotherapy which formed the basis treatment for R/R WM is slowly being replaced by novel targeted agents. These therapies, including Bruton\'s tyrosine kinase inhibitors, proteasome inhibitors, and B-cell lymphoma 2 inhibitors, have widened the landscape of management. Emerging therapies currently under investigation, such as bispecific T-cell engagers, chimeric antigen T-cell receptor therapy, and novel small molecule inhibitors, have additionally shown the potential to improve response and survival. The treatment of R/R WM has greatly evolved, in large part due to a greater understanding of the biology of WM, and the evaluation of novel targeted agents in the basket trials of NHL, showing early activity in the small WM cohorts. Combination regimens with these established and emerging novel therapies have the potential to further improve disease control and induce higher rates of deep responses. Strategies aimed at altering the disease trajectory would require randomized controlled trials to provide relevant data on optimal integration and sequencing of more effective and tolerable regimens earlier in the disease course.

BACKGROUND: Waldenström\'s macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL.
METHODS: An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström\'s macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein.
CONCLUSIONS: Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion.

BACKGROUND: Pleural effusion, especially bilateral bloody pleural effusion, is a rare complication of Waldenström macroglobulinemia (WM). Pleural effusion in patients with WM has many causes, such as infection, tumor invasion of the pleura, and rupture of the thoracic duct or its branches. Patients with WM presenting to the respiratory department with chest tightness and shortness of breath need more differential diagnosis by respiratory physicians, which is helpful for effective treatment. Herein, we present a case of MV diagnosis in a patient with bilateral bloody pleural effusion.
METHODS: Our patient is a 59-year-old man with WM presenting as having bilateral bloody pleural effusion.
METHODS: The patient was treated with pleural effusion drainage. After confirming the diagnosis, the patient was treated with rituximab, cyclophosphamide, and dexamethasone.
RESULTS: Following these treatments, the patient\'s symptoms improved, and ultrasound showed a decrease in pleural effusion.
CONCLUSIONS: Despite its favorable prognosis, the cause of pleural effusion in a patient with WM can be challenging to diagnose. The cause of pleural effusion should be considered a differential diagnosis when diagnosing patients diagnosed with WM.