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1.
Am J Case Rep ; 25: e940963, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38437184

RESUMO

BACKGROUND Non-IgM lymphoplasmacytic lymphoma (LPL) is a rare subtype of LPL, constituting less than 5% of the cases, and is often associated with IgG, IgA, or light chain paraproteins and is rarely a non-secretor. Non-IgM LPL remains poorly studied, and the differential diagnosis from other small B-cell lymphomas with plasmacytic differentiation and plasma cell neoplasm is challenging. CASE REPORT A 67-year-old woman presented with weight loss, persistent anemia, and borderline leukopenia. Serum protein electrophoresis and immunofixation demonstrated a faint IgG and kappa band against a dense polyclonal background. Bone marrow biopsy revealed hypercellular marrow with involvement by abnormal B cells with undetectable surface and cytoplasmic immunoglobulin light chains. Interestingly, these B cells showed no expression of light chains or production of IgG and IgM; however, they showed production of intracytoplasmic IgA. The concomitant neoplastic plasma cells also displayed no definitive light chain expression. Both IgH and IgK gene rearrangements were positive for clonal process. Molecular studies showed positive MYD88 L265P mutation and CXCR4 mutation (c.1013C>G). The overall findings confirmed marrow involvement by non-IgM LPL. The patient received 6 cycles of rituximab and bendamustine treatment, and no residual marrow involvement was found on the follow-up bone marrow biopsy. CONCLUSIONS We report a non-IgM LPL case featuring no light chain production and no heavy chain secretion, which we believe is the first reported case of this kind in the literature.


Assuntos
Linfoma de Células B , Linfoma , Macroglobulinemia de Waldenstrom , Feminino , Humanos , Idoso , Macroglobulinemia de Waldenstrom/diagnóstico , Imunoglobulina A , Imunoglobulina G
3.
Chest ; 165(2): e39-e43, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38336442

RESUMO

CASE PRESENTATION: A 74-year-old man presented to our department with progressive dyspnea on exertion over the last year. The patient did not report any other symptoms. He had previously smoked with a 60 pack-year history. He worked in an office and did not report any environmental, occupational, or domestic exposures. His history included asymptomatic Waldenström's macroglobulinemia that was diagnosed 18 months before respiratory symptoms. He was not receiving any treatment and was monitored regularly by the hematology department.


Assuntos
Macroglobulinemia de Waldenstrom , Masculino , Humanos , Idoso , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Dispneia/diagnóstico , Dispneia/etiologia
6.
BMJ Case Rep ; 17(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38176750

RESUMO

IgM monoclonal gammopathies such as IgM myeloma and Waldenström macroglobulinaemia are distinct haematological conditions; however, differentiating between these entities can often present as a challenge.In this review, we explore the challenging diagnosis and treatment of IgM myeloma in a patient presenting with unexplained macrocytic anaemia, elevated serum protein and IgM levels in the absence of t(11;14) and lytic bone lesions that are classically associated with the diagnosis of IgM myeloma. The diagnosis was established based on 40% monoclonal plasma cell population on a bone marrow biopsy, gain of 1q21 on fluorescence in situ hybridisation, cyclin D1 positivity and absence of MYD88 mutation.


Assuntos
Mieloma Múltiplo , Macroglobulinemia de Waldenstrom , Humanos , Mieloma Múltiplo/patologia , Medula Óssea/patologia , Plasmócitos/patologia , Macroglobulinemia de Waldenstrom/genética , Imunoglobulina M
7.
BMJ Case Rep ; 17(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182164

RESUMO

Bing-Neel syndrome (BNS) is a very rare manifestation of Waldenström macroglobulinaemia (WM), in which lymphoplasmacytic cells invade the central nervous system. The clinical presentation includes symptoms of headaches, visual floaters, neuropathy, seizures and gait abnormalities. Here, we describe an elderly woman, who presented with complaints of visual floaters, progressive neuropathy and cognitive changes. Workup including a bone marrow biopsy confirmed the diagnosis of WM. Shortly afterwards, the patient experienced a seizure leading to hospitalisation, which revealed a right frontal lobe lesion on brain MRI. A biopsy of the lesion showed a small B cell lymphoma positive for an MYD88 mutation, confirming BNS. The patient was initially treated with ibrutinib, before transitioning to zanubrutinib. However, she developed disease progression necessitating radiotherapy with lenalidomide and rituximab maintenance therapy, which achieved remission. This case sheds light on the diagnosis and management of a very rare complication of a rare disease.


Assuntos
Linfoma de Células B , Macroglobulinemia de Waldenstrom , Idoso , Feminino , Humanos , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Convulsões , Sistema Nervoso Central , Cefaleia
8.
JBJS Case Connect ; 14(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38181166

RESUMO

CASE: We present a 63-year-old patient diagnosed with Waldenstrom macroglobulinemia (WM) through histopathology of bone tissue after total knee arthroplasty for routine osteoarthritis. The patient, surgical team, and the pathologist were unaware of this diagnosis before the surgery. CONCLUSION: The cost-effectiveness of routine histopathologic examination of bone cuts and synovial samples after total joint arthroplasty continues to be a source of debate. Our case highlights an example of the utility of histopathology because it led to the early detection of WM, resulting in prompt treatment to improve quality of life.


Assuntos
Artroplastia do Joelho , Osteoartrite , Macroglobulinemia de Waldenstrom , Humanos , Pessoa de Meia-Idade , Macroglobulinemia de Waldenstrom/diagnóstico , Qualidade de Vida , Osso e Ossos
9.
Clin Lab ; 70(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38213207

RESUMO

BACKGROUND: We report through this case, the exceptional occurrence of Waldenström's macroglobulinemia in a renal transplant. METHODS: A 65-year-old diabetic man, who had a kidney transplant in 2008, presented to the hospital in 2020 for ketoacid decompensation. The blood ionogram showed hyperproteinemia at 102 g/L. Electrophoresis and immunofixation of serum proteins revealed a monoclonal immunoglobulin of IgM Kappa isotype numbered at 46 g/L. Confirmation of Waldenström's disease was made by myelogram and immunophenotyping of tumor cells. RESULTS: The diagnosis adopted for our case is Waldenström's disease which occurred 12 years after the kidney transplantation. CONCLUSIONS: Post-transplant lymphoproliferative syndromes are secondary to immunosuppressive therapy, the main concern in this case is the involvement of the graft with the risk of losing its function, hence the interest of monitoring and identifying any hyperproteinemia.


Assuntos
Transplante de Rim , Macroglobulinemia de Waldenstrom , Masculino , Humanos , Idoso , Transplante de Rim/efeitos adversos , Macroglobulinemia de Waldenstrom/diagnóstico , Imunoglobulina M , Isotipos de Imunoglobulinas , Anticorpos Monoclonais
10.
Int J Surg Pathol ; 32(1): 5-10, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37093763

RESUMO

Lymphoplasmacytic lymphoma often needs to be differentiated from other B-cell lymphomas with plasmacytic differentiation, especially marginal zone cell lymphoma. Molecular detection of MYD88 p.L265P hotspot mutation supports the diagnosis of lymphoplasmacytic lymphoma since it is seen in about 90% of such lymphoma, which is much higher than other B-cell lymphomas. MYD88 p.L265P is a gain-of-function mutation that enhances the activity of the NF-κB signaling pathway and therefore drives lymphomagenesis. Other mutations in MYD88 are rarely reported. This study aims to report an unusual MYD88 in-frame deletion in an aggressive lymphoplasmacytic neoplasm. This is an IgM-positive, CD5- and CD10-negative mature B-cell lymphoma with prominent plasmacytic differentiation and aggressive features. The clinical and pathologic findings were most consistent with lymphoplasmacytic lymphoma. Next-generation sequencing identified an unusual MYD88 in-frame deletion in the absence of the hotpot p.L265P mutation. Other concurrent pathogenic mutations also include truncating mutations of TRAF3, which is a negative regulator of the NF-κB signaling pathway, and a missense mutation of TP53. Karyotype analysis showed complex karyotypes, including chromosome 6q deletion. By searching literature and online cancer databases, we identified only 8 other mature B-cell lymphomas with MYD88 in-frame deletions, but none of them was diagnosed with lymphoplasmacytic lymphoma. Recognizing such in-frame deletions is necessary to help understand the mutational spectrum of MYD88 in B-cell lymphomas. It remains to be further investigated whether such MYD88 in-frame deletions are also overrepresented in lymphoplasmacytic lymphoma among other B-cell lymphomas.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Macroglobulinemia de Waldenstrom , Humanos , Fator 88 de Diferenciação Mieloide/genética , Fator 3 Associado a Receptor de TNF/genética , NF-kappa B/genética , Mutação , Linfoma de Zona Marginal Tipo Células B/patologia , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/patologia , Cariótipo , Proteína Supressora de Tumor p53/genética
11.
Drugs ; 84(1): 17-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38055179

RESUMO

With the worldwide approval of the oral covalent Bruton tyrosine kinase (BTK) inhibitors ibrutinib and zanubrutinib for treating patients with Waldenström macroglobulinemia (WM), targeted agents have certainly taken center stage in the therapeutic landscape of WM. This review discusses the biological and clinical data supporting current and up-and-coming targeted agents in WM. Bruton tyrosine kinase inhibitors induce fast, deep, and durable responses in patients with WM, comparable to chemoimmunotherapy; however, there is a glaring absence of comparative studies between these regimens. The high response and progression-free survival rate and the ease of administration of BTK inhibitors must be balanced against their specific adverse-event profile with unique toxicity (e.g., bleeding and cardiac arrhythmia) and the indefinite duration of the therapy. Novel targeted agents of interest include BCL2 antagonists (e.g., venetoclax and sonrotoclax) and non-covalent BTK inhibitors (e.g., pirtobrutinib and nemtabrutinib), among others. The therapeutic landscape of patients with WM will benefit from the robust participation of patients in clinical trials.


Assuntos
Antineoplásicos , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos
13.
Ann Hematol ; 103(2): 553-563, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37951851

RESUMO

We performed a molecular analysis of formalin-fixed paraffin embedded and decalcified bone marrow trephine biopsies of 41 patients with a B-cell disorder with lymphoplasmacytic differentiation to enable a more precise diagnosis and to describe potentially prognostic and therapeutic relevant mutations. Analysis was performed with a commercially available next-generation sequencing (NGS) lymphoma panel (Lymphoma Solution, SophiaGenetics). Results were correlated with clinical and pathological parameters. Our group covered a spectrum of B-cell disorders with plasmacytic differentiation ranging from Waldenstroem's macroglobulinemia (WM), to small-B-cell lymphomas with plasmacytic differentiation (SBCL-PC) to IgM myeloma (MM). The most helpful diagnostic criteria included morphology and immuno-phenotype as a prerequisite for the interpretation of molecular analysis. MYD88 mutation was present in nearly all WM, but also in 50% of SBCL-PCs, while MM were consistently negative. Driver mutations, such as TP53, were already detectable early in the course of the respective diseases indicating a higher risk of progression, transformation, and reduced progression-free survival. In addition, we report on a novel BIRC3 frameshift mutation in one case of a progressive WM. Our data indicate that patients with LPL/WM might benefit from thorough pathological work-up and detailed molecular analysis in terms of precise diagnosis and targeted treatment allocation.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma , Macroglobulinemia de Waldenstrom , Humanos , Linfoma/patologia , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Medula Óssea/patologia , Mutação , Fator 88 de Diferenciação Mieloide/genética
14.
Blood ; 143(7): 582-591, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37971194

RESUMO

ABSTRACT: Concurrent Bruton tyrosine kinase and BCL2 inhibition has not yet been investigated in Waldenström macroglobulinemia (WM). We performed an investigator-initiated trial of ibrutinib and venetoclax in symptomatic treatment-naïve patients with MYD88-mutated WM. Patients received ibrutinib 420 mg once daily (cycle 1), followed by a ramp-up of venetoclax to 400 mg daily (cycle 2). The combination was then administered for 22 additional 4-week cycles. The attainment of very good partial response (VGPR) was the primary end point. Forty-five patients were enrolled in this study. The median baseline characteristics were as follows: age 67 years, serum IgM 43 g/L, and hemoglobin 102 g/L. Seventeen patients (38%) carried CXCR4 mutations. Nineteen patients (42%) achieved VGPR. Grade 3 or higher adverse events included neutropenia (38%), mucositis (9%), and tumor lysis syndrome (7%). Atrial fibrillation occurred in 3 (9%), and ventricular arrhythmia in 4 (9%) patients that included 2 grade 5 events. With a median follow-up of 24.4 months, the 24-month progression-free survival (PFS) and overall survival (OS) rates were 76% and 96%, respectively, and were not impacted by CXCR4 mutations. The median time on therapy was 10.2 months, and the median time after the end of therapy (EOT) was 13.3 months. Eleven of the 12 progression events occurred after EOT, and the 12-month PFS rates after EOT were 79%; 93% if VGPR was attained, and 69% for other patients (P = .12). Ibrutinib and venetoclax induced high VGPR rates and durable responses after EOT, although they were associated with a higher-than-expected rate of ventricular arrhythmia in patients with WM, leading to early study treatment termination. This trial was registered at www.clinicaltrials.gov as #NCT04273139.


Assuntos
Adenina/análogos & derivados , Compostos Bicíclicos Heterocíclicos com Pontes , Sulfonamidas , Macroglobulinemia de Waldenstrom , Humanos , Idoso , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Piperidinas , Arritmias Cardíacas
15.
J Neurol ; 271(3): 1320-1330, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37979093

RESUMO

INTRODUCTION: Anti-MAG neuropathies are associated with an IgM monoclonal gammopathy of undetermined significance (MGUS) or with a malignant haemopathy. Our objective was to determine whether the presence of a haemopathy or somatic mutations of MYD88 and CXCR4 genes influences disease presentation and response to rituximab (RTX). METHODS: We included 79 patients (mean age 74 years, disease duration 9.68 years) who had a bone marrow aspiration with morphologic and immunophenotypic analysis. MYD88L265P and CXCR4 mutations were analysed in peripheral B cells. Information collected included: inflammatory neuropathy cause and treatment sensory sum score (ISS), MRC testing, overall neuropathy limitation scale (ONLS), Rash-built Overall Disability Score (RODS), ataxia score, anti-MAG titres, peak IgM dosage, neurofilament light chain levels, motor and sensory amplitudes, motor unit index (MUNIX) and motor unit size index (MUSIX) sum scores. Efficacy of RTX was evaluated at 12 months in 26 patients. RESULTS: Malignant haematological disorders were discovered in 17 patients (22%): 13 Waldenstrom macroglobulinemia, 3 marginal zone lymphoma and one mantle cell lymphoma. MYD88L265P mutation was detected in 29/60 (48%) patients and CXCR4 in 1 single patient. Disease severity, biological and electrophysiological data and response to RTX were comparable in patients with MGUS/lymphoma and patients with/without MYD88L265P mutation. ISS was lower and MUSIX higher in patients improved by RTX. CONCLUSIONS: MYD88L265P mutation and underlying haemopathies are not predictive of a more severe disease. However, in cases of resistant and progressive neuropathy, they provide an opportunity to prescribe newly available drugs such as Bruton tyrosine kinase inhibitors.


Assuntos
Linfoma , Gamopatia Monoclonal de Significância Indeterminada , Macroglobulinemia de Waldenstrom , Adulto , Idoso , Humanos , Imunoglobulina M , Mutação/genética , Fator 88 de Diferenciação Mieloide/genética , Receptores CXCR4/genética , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética
16.
J Cutan Pathol ; 51(2): 135-139, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37877413

RESUMO

Lymphoplasmacytic lymphoma (LPL) is a rare variant of non-Hodgkin lymphoma, accounting for <1% of cases. Skin involvement in LPL is quite rare-accounting for approximately 5% of extramedullary disease-and includes a variety of clinical morphologies, such as erythematous-to-violaceous plaques, violaceous nodules or tumors, and ulceration at various anatomical sites. Herein, we report the case of a 45-year-old Korean woman who presented with generalized erythematous indurated plaques and pendulous skin growths, which were asymptomatic, with marked diffuse infiltration of lymphocytes and plasma cells in the dermis. Immunohistochemical studies revealed that the lymphoid cells expressed CD3, CD79a, and cytoplasmic IgG, but lacked CD10 and IgM. Moreover, kappa light chain restriction and monoclonal immunoglobulin heavy chain gene rearrangement were observed. Upon further workup, lymphoma involvement was reported in multiple lymph nodes, including those in the cervical and axillary regions. This case shows a unique form of cutaneous LPL clinically presenting as acquired cutis laxa, emphasizing the dermatologists' need to be vigilant for variant forms of this disease.


Assuntos
Cútis Laxa , Linfoma de Células B , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Macroglobulinemia de Waldenstrom , Feminino , Humanos , Pessoa de Meia-Idade , Cútis Laxa/patologia , Neoplasias Cutâneas/patologia , Linfoma Cutâneo de Células T/patologia , Plasmócitos/patologia , Macroglobulinemia de Waldenstrom/diagnóstico
19.
Br J Haematol ; 204(1): 177-185, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37726004

RESUMO

Monoclonal immunoglobulin M-associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9-year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non-Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM-associated disorders (including cold agglutinin disease [CAD], anti-MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild-type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin-related symptoms alone at a median of 38 days (range: 6-239) from cryoglobulin detection. At a median follow-up of 3 years (range: 0-10), 3-year cryoglobulinaemia-treatment-free survival was 77% (95% CI: 68%-84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia-related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62-341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13-7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.


Assuntos
Crioglobulinemia , Linfoma de Células B , Gamopatia Monoclonal de Significância Indeterminada , Macroglobulinemia de Waldenstrom , Humanos , Crioglobulinas , Crioglobulinemia/etiologia , Macroglobulinemia de Waldenstrom/patologia , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Imunoglobulina M , Anticorpos Monoclonais , Paraproteínas
20.
Adv Ther ; 41(2): 672-685, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38079089

RESUMO

INTRODUCTION: Waldenström's macroglobulinemia (WM) is a rare malignant B cell lymphoma which occurs in around 1-2% of all hematologic tumors. Ibrutinib was approved in China for WM on the basis of two global pivotal studies which enrolled no Chinese patients. The aim of this study was to determine the efficacy, safety, and pharmacokinetics of ibrutinib in Chinese patients with relapsed or refractory (r/r) WM. METHODS: This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM. RESULTS: Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively. CONCLUSIONS: Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04042376.


Assuntos
Linfoma de Células B , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Piperidinas/uso terapêutico , Adenina/uso terapêutico
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