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1.
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
2.
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
3.
Ann Diagn Pathol ; 73: 152372, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39208652

RESUMO

Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent MYD88 and CXCR4 mutations and fluorescence in-situ hybridization showed CCND1 translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas.

4.
Int J Mol Sci ; 25(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38542207

RESUMO

The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma. Covalent BTKi (namely ibrutinib, acalabrutinib, and zanubrutinib) functions by irreversibly blocking BTK through covalent binding to the cysteine residue 481 (Cys-481) in the ATP-binding domain. Despite the high efficacy and safety of BTKi treatment, a significant fraction of patients affected by B cell malignancies who are treated with these drugs experience disease relapse. Several mechanisms of resistance to covalent BTKi, including Cys-481 mutations of BTK, have been investigated in B cell malignancies. Non-covalent BTKi, such as pirtobrutinib, have been developed and proven effective in patients carrying both Cys-481-mutated and unmutated BTK. Moreover, targeting BTK with proteolysis-targeting chimeras (PROTACs) represents a promising strategy to overcome resistance to BTKi in B cell neoplasms.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma Difuso de Grandes Células B , Humanos , Adulto , Tirosina Quinase da Agamaglobulinemia , Ligantes , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico
5.
Ann Hematol ; 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37414960

RESUMO

Waldenström macroglobulinemia (WM) is a chronic B-cell lymphoproliferative disorder characterized by lymphoplasmacytic cell overgrowth in the bone marrow and increased secretion of IgM immunoglobulins into the serum. Patients with WM have a variety of clinical outcomes, including long-term survival but inevitable recurrence. Recent advances in disease knowledge, including molecular and genetic principles with the discovery of MYD88 and CXCR4 mutations, have rapidly increased patient-tolerable treatment options. WM patients may benefit from chemotherapy regimens that include rituximab-based regimens, alkylating drugs, proteasome inhibitors, monoclonal antibodies, and drugs targeting Bruton tyrosine kinase inhibitors. In light of these advancements, patients can now receive treatment customized to their specific clinical characteristics, focusing on enhancing the depth and durability of their response while limiting the adverse effects. Despite the rapidly developing therapeutic armament against WM, a lack of high-quality evidence from extensive phase 3 trials remains a significant challenge in the research. We believe clinical outcomes will keep improving when new medicines are introduced while preserving efficacy and minimizing toxicity.

6.
Acta Haematol ; 146(5): 384-390, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36917966

RESUMO

INTRODUCTION: Waldenström macroglobulinemia (WM) represents a subset of lymphoplasmacytic lymphoma (LPL) with the immunoglobulin (Ig)M paraprotein. MYD88 L265P and CXCR4 mutations are common mutations in WM patients, and mutations in ARID1A and KMT2D (MLL2) have also been reported. However, little information has been accumulated on genetic changes in LPL with other paraproteins like IgG. METHODS: We therefore aimed to evaluate genetic differences between WM and LPL with non-IgM paraprotein (non-IgM-type LPL) using targeted next-generation sequencing (NGS) in 20 Japanese patients (10 with WM, 10 with non-IgM-type LPL). RESULTS: Mutations were detected in ARID1A (10%), CXCR4 (20%), MYD88 (90%), and KMT2D (0%) for WM patients and in ARID1A (10%), CXCR4 (20%), MYD88 (70%), and KMT2D (10%) for non-IgM-type LPL patients. No significant differences were identified. No mutations were detected in NOTCH2, PRDM1, CD274 (PD-L1), PDCD1LG2 (PD-L2), RAG2, MYBBP1A, TP53, or CD79B. DISCUSSION: Mutant allele frequency in MYD88 L265P did not differ significantly between WM and non-IgM-type LPL. Most mutations detected by NGS were subclonal following MYD88 L265P, although one non-IgM-type LPL patient harbored only CXCR4 S338X mutation. Our NGS analyses reveal genetic characteristics in LPL patients and suggest genetic similarities between these two subsets of LPL, WM and non-IgM-type.


Assuntos
Linfoma de Células B , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/patologia , Fator 88 de Diferenciação Mieloide/genética , Mutação , Paraproteínas/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Proteínas de Ligação a RNA/genética
7.
Rinsho Ketsueki ; 64(1): 54-59, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36775308

RESUMO

A 61-year-old female was referred to our hospital because of pancytopenia and febrile neutropenia. On admission, computed tomography showed mild hepatosplenomegaly and intra-abdominal abscess formation in the right pelvic region; however, no lymphadenopathy was found. Bone marrow (BM) examination showed severe fibrosis by silver staining. Several small- to medium-sized lymphocytes with a constriction in the nuclei were observed, exhibiting CD3 (-), CD10 (-), CD20 (+), BCL-2 (+-), and CD138 (+-). Genetic testing revealed that BM cells were positive for MYD88 mutation and positive for IgH rearrangement, whereas neither JAK2 nor CALR mutation was positive. A diagnosis of BM infiltration of lymphoplasmacytic lymphoma (LPL) was made. Rituximab monotherapy was administered once a week for four times. BM examination 4 weeks after the end of treatment showed that lymphoma cells had disappeared and that myelofibrosis had been almost gone. The MYD88 mutation of BM turned out to be negative at that moment.


Assuntos
Linfoma de Células B , Mielofibrose Primária , Macroglobulinemia de Waldenstrom , Feminino , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Fator 88 de Diferenciação Mieloide/genética , Medula Óssea/patologia , Linfoma de Células B/diagnóstico , Rituximab , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética
8.
Rinsho Ketsueki ; 64(4): 245-249, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37121766

RESUMO

A 93-year-old woman was diagnosed with lymphoplasmacytic lymphoma (LPL) with circulating tumor cells in her peripheral blood after presenting with anemia. LPL progressed eight months later, with anemia worsening and tumor cells increasing to 66% of leukocytes. She began tirabrutinib at a low dose (80 mg daily: 17% of the standard dose) because she preferred to maintain her quality of life (QOL). Within three weeks, she was free of transfusion dependency and had a partial response with the disappearance of peripheral tumor cells. The dosage of tirabrutinib was increased to 240 mg daily because it was well tolerated. She has been on the treatment for 13 months with no adverse effects. Tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, has been reported to have promising efficacy for LPL, but it also has a high incidence of dermatological toxicity, which may impair QOL. Low-dose tirabrutinib initiation may be effective and assist elderly patients with LPL in maintaining their QOL.


Assuntos
Linfoma de Células B , Macroglobulinemia de Waldenstrom , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Linfoma de Células B/tratamento farmacológico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Pirimidinas/uso terapêutico
9.
Br J Haematol ; 196(6): 1362-1368, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34959252

RESUMO

Lymphoplasmacytic lymphoma (LPL) not fulfilling the WHO diagnostic criteria (2017) for Waldenstrom's macroglobulinemia (WM) (named non-WM LPL) is a rare disease and only a few systematic studies have been published. Here, we present a population-based study of non-WM LPL focusing on diagnostic difficulties, patient characteristics, and outcome. From 1511 patients included in the Swedish Lymphoma Registry 1 Jan 2000 - 31 Dec 2014 with a diagnosis of WM/LPL, we could confirm the diagnosis of non-WM LP in only 33 patients. The median age at diagnosis was 69 years. A paraprotein was found in most (IgG in 54%, IgA in 15%) and 12% of the cases were non-secretory. Compared with the WM patients, the non-WM LPL patients were younger, had more adverse prognostic factors such as elevated LDH, anaemia, and lymphocytosis at diagnosis. In addition, the non-WM LPL patients more often were symptomatic and received treatment at diagnosis. The overall survival (OS) did not significantly differ between the non-WM LPL and WM groups (P = 0.247), with a median survival time of 71 and 96 months, respectively. To conclude, we found differences in clinical features between WM and non-WM LPL, but no difference in survival.


Assuntos
Linfoma de Células B , Linfoma , Macroglobulinemia de Waldenstrom , Humanos , Sistema de Registros , Suécia/epidemiologia , Macroglobulinemia de Waldenstrom/tratamento farmacológico
10.
Br J Haematol ; 196(5): 1205-1208, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34738239

RESUMO

Contemporary diagnosed WM patients, compared to the general population, continue to experience excess mortality regardless of having survived up to 15 years post-diagnosis. This gradual increase in excess mortality might result from the incurable nature of this disease characterized by multiple relapses throughout the disease course with limited efficacious treatment options in the released/refractory setting.


Assuntos
Macroglobulinemia de Waldenstrom/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Risco , Análise de Sobrevida , Macroglobulinemia de Waldenstrom/diagnóstico
11.
Br J Haematol ; 196(3): 660-669, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34605017

RESUMO

It is unclear how treatment advances impacted the population-level survival of patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia (LPL/WM). Therefore, we assessed trends in first-line therapy and relative survival (RS) among patients with LPL/WM diagnosed in the Netherlands between 1989 and 2018 (N = 6232; median age, 70 years; 61% males) using data from the nationwide Netherlands Cancer Registry. Patients were grouped into three age groups (<65, 66-75 and >75 years) and four calendar periods. Overall, treatment with anti-neoplastic agents within 1 year post-diagnosis gradually decreased over time, following a broader application of an initial watch-and-wait approach. Approximately 40% of patients received anti-neoplastic therapy during 2011-2018. Furthermore, use of chemotherapy alone decreased over time, following an increased application of chemoimmunotherapy. Detailed data among 1596 patients diagnosed during 2014-2018 revealed that dexamethasone-rituximab-cyclophosphamide was the most frequently applied regimen; its use increased from 14% to 39% between 2014 and 2018. The 5-year RS increased significantly over time, particularly since the introduction of rituximab in the early-mid 2000s. The 5-year RS during 1989-1995 was 75%, 65%, and 46% across the age groups compared to 93%, 85%, and 79% during 2011-2018. However, the survival improvement was less pronounced after 2011. Collectively, the impressive survival improvement may be accounted for by broader application of rituximab-containing therapy. The lack of survival improvement in the post-rituximab era warrants studies across multiple lines of therapy to further improve survival in LPL/WM.


Assuntos
Macroglobulinemia de Waldenstrom/mortalidade , Macroglobulinemia de Waldenstrom/terapia , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Gerenciamento Clínico , Feminino , História do Século XX , História do Século XXI , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Países Baixos/epidemiologia , Prognóstico , Vigilância em Saúde Pública , Sistema de Registros , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/história
12.
J Cutan Pathol ; 49(2): 176-182, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34617316

RESUMO

Cutaneous reactive angiomatosis, a group of disorders defined by benign vascular proliferation, is associated with a number of systemic processes, including intravascular occlusion by cryoproteins. We report a case of a 64-year-old female patient who presented with a 1-year history of nontender petechiae of the bilateral arms and lower legs. Dermoscopic evaluation showed increased vascularity with a globular pattern. Over a period of months, her findings progressed to erythematous to violaceous plaques with admixed hypopigmented stellate scarring of the bilateral lower extremities, forearms, and lateral neck. Biopsy showed increased thin-walled, small dermal blood vessels with focal inter-anastamosis. Some vessels were occluded by eosinophilic globules suspicious for cryoprotein. Subsequent laboratory studies confirmed a diagnosis of type 1 cryoglobulinemia, prompting a bone marrow biopsy that revealed lymphoplasmacytic lymphoma. Herein, we report the fourth case of angiomatosis secondary to intravascular cryoproteins as the initial presentation of an underlying hematologic malignancy. We also present a review of the literature and emphasize the need for thorough initial workup and close and prolonged clinical monitoring for underlying systemic disease in these patients.


Assuntos
Angiomatose/patologia , Crioglobulinemia/diagnóstico , Neoplasias Cutâneas/patologia , Macroglobulinemia de Waldenstrom/diagnóstico , Crioglobulinas/metabolismo , Dermoscopia , Feminino , Humanos , Pessoa de Meia-Idade
13.
J Infect Chemother ; 28(2): 279-282, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34580008

RESUMO

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words).


Assuntos
Linfoma , Toxoplasma , Toxoplasmose Cerebral , Encéfalo/diagnóstico por imagem , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Masculino , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/tratamento farmacológico
14.
Rinsho Ketsueki ; 63(6): 619-625, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35831197

RESUMO

B-cell lymphoma accounts for approximately 70% of malignant lymphomas, and its treatment outcomes have drastically improved after the introduction of rituximab. Most patients with diffuse large B-cell lymphoma (DLBCL) are successfully treated with the current standard chemotherapeutic regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, 30-40% of patients with DLBCL have unsatisfactory treatment outcomes. Molecular genetic research has greatly contributed to the identification of pathogenic mechanisms of lymphoma and factors leading to poor prognosis. Thus, novel agents for targeting factors in key signaling pathways, relevant targeted antigens, and epigenetic enzymes have been developed. Additionally, development of immunotherapies such as anti-CD19-chimeric antigen receptor (CAR) T cell and bispecific antibody therapy have led to a paradigm shift for relapsed or refractory DLBCL treatments. Herein, we discuss the results of clinically impactful studies on the treatment strategies of B-cell lymphoma, including DLBCL, follicular lymphoma, and lymphoplasmacytic lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
15.
Br J Haematol ; 195(2): 210-216, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34340248

RESUMO

Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow-up of 9·5 [8·1-11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and ß2 -microglobulin (ß2 M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time-to-progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT ) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7-8·7) vs. 4·7 (2·4-7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C-X-C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT , P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and ß2 M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre-emptive intervention in this patient population.


Assuntos
Hemoglobinas/análise , Fator 88 de Diferenciação Mieloide/genética , Macroglobulinemia de Waldenstrom/genética , Microglobulina beta-2/sangue , Idoso , Biomarcadores/análise , Progressão da Doença , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Valor Preditivo dos Testes , Receptores CXCR4/genética , Estudos Retrospectivos , Fatores de Risco , Sobrevida , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/patologia
16.
Rinsho Ketsueki ; 62(10): 1493-1498, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732622

RESUMO

Bing-Neel syndrome (BNS), which presents with a variety of neurological complications, is a rare manifestation of the lymphoplasmacytic lymphoma (LPL) and is characterized by the infiltration of LPL cells into the central nervous system. In this study, we report the case of a patient with BNS, which was confirmed by detecting MYD88 L265P mutation in the cerebrospinal fluid (CSF) cells. A 74-year-old patient was diagnosed with IgG-variant LPL. He achieved a very good partial response to the treatment with rituximab and bendamustine (RB) and was stable for over 5 years, when presenting a slowly progressive motor deficit in the lower limbs. It was difficult to confirm BNS from morphological analysis of the CSF cells. After detecting MYD88 L265P mutation in the CSF cells, he was subsequently diagnosed with BNS and treated with RB and intrathecal chemotherapy, resulting in rapid clinical improvement. With the onset of neurological manifestation during the clinical course of LPL, the detection of MYD88 L265P mutation in the CSF cells could be helpful for the diagnosis and management of BNS.


Assuntos
Fator 88 de Diferenciação Mieloide , Macroglobulinemia de Waldenstrom , Idoso , Humanos , Imunoglobulina G , Masculino , Mutação , Fator 88 de Diferenciação Mieloide/genética , Rituximab , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética
17.
Rinsho Ketsueki ; 62(8): 1139-1148, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497201

RESUMO

Waldenström's macroglobulinemia or lymphoplasmacytic lymphoma (WM/LPL) is a rare subtype of indolent B-cell lymphoma with plasmacytic differentiation. Owing to its rarity, the pathogenesis, biology, and standard of care have not been established. In 2012 the MYD88 L265P mutation is proven as the major oncogenesis in WM/LPL; therefore, the pathogenesis and underlying biology of WM/LPL have been drastically explored. Furthermore, treatment options have also been developed, and Bruton's tyrosine kinase (BTK) inhibitor has been recently approved for untreated and relapsed/refractory WM/LPL in August 2020 in Japan. In this article, after a brief review of the clinical and biological characteristics of WM/LPL, we discuss the ideal therapeutic algorithm, including novel BTK inhibitor.


Assuntos
Linfoma de Células B , Macroglobulinemia de Waldenstrom , Algoritmos , Humanos , Japão , Mutação , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética
18.
Br J Haematol ; 188(3): 394-403, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31468508

RESUMO

Ibrutinib-related data in Waldenström macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n = 67 (84%), treatment-naïve, n = 13 (16%)] with WM, evaluated consecutively at Mayo Clinic, who received ibrutinib off-study after its approval in 2015 for WM. Overall response rate (ORR) was 91%; major-response rate (MRR) was 78%. The median time to first response and best response was 2·9 [95% confidence interval (CI): 2-4] and 5·7 (95% CI: 4-12) months, respectively. The median follow-up was 19 (95% CI: 14-21) months; 18-month progression-free survival (PFS) was 82%. The median time on therapy was 12·5 (95% CI: 9·3-16·7) months, and the median duration-of-response was 32 (range: 23-32) months. Twenty-five patients (31%) had discontinued therapy at last follow-up (68% due to treatment-related toxicities) and 18% of patients required dose reduction. Fatigue (12%) and atrial-fibrillation (11%) were common non-haematological toxicities. IgM rebound occurred in 36% of patients who abruptly discontinued ibrutinib. Following ibrutinib discontinuation, 84% of patients received subsequent treatment, achieving an ORR of 57% and MRR of 50%. The median PFS from commencement of subsequent salvage therapy was 18 months. Ibrutinib therapy, outside of clinical trials, is effective in WM, but is associated with toxicities and challenges, including IgM rebound and a high drug discontinuation rate for reasons other than disease progression.


Assuntos
Antineoplásicos/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Imunoglobulina M/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Piperidinas , Padrões de Prática Médica/estatística & dados numéricos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Terapia de Salvação/métodos , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/imunologia
19.
Br J Haematol ; 189(6): 1107-1118, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32090327

RESUMO

Data on cause-specific mortality after lymphoplasmacytic lymphoma (LPL) and Waldenström macroglobulinaemia (WM) are lacking. We identified causes of death amongst 7289 adults diagnosed with incident first primary LPL (n = 3108) or WM (n = 4181) during 2000-2016 in 17 USA population-based cancer registries. Based on 3132 deaths, 16-year cumulative mortality was 23·2% for lymphomas, 8·4% for non-lymphoma cancers and 14·7% for non-cancer causes for patients aged <65 years at diagnosis of LPL/WM, versus 33·4%, 11·2% and 48·7%, respectively, for those aged ≥75 years. Compared with the general population, patients with LPL/WM had a 20% higher risk of death due to non-cancer causes (n = 1341 deaths, standardised mortality ratio [SMR] 1·2, 95% confidence interval [CI] 1·1-1·2), most commonly from infectious (n = 188; SMR 1·8, 95% CI 1·6-2·1), respiratory (n = 143; SMR 1·2, 95% CI 1·0-1·4), and digestive (n = 80; SMR 1·8, 95% CI 1·4-2·2) diseases, but no excess mortality from cardiovascular diseases (n = 477, SMR 1·1, 95% CI 1·0-1·1). Risks were highest for non-cancer causes within 1 year of diagnosis (n = 239; SMR<1year 1·3, 95% CI 1·2-1·5), declining thereafter (n = 522; SMR≥5years 1·1, 95% CI 1·1-1·2). Myelodysplastic syndrome/acute myeloid leukaemia deaths were notably increased (n = 46; SMR 4·4, 95% CI 3·2-5·9), whereas solid neoplasm deaths were only elevated among ≥5-year survivors (n = 145; SMR≥5years 1·3, 95% CI 1·1-1·5). This work identifies new areas for optimising care and reducing mortality for patients with LPL/WM.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Sistema de Registros , Macroglobulinemia de Waldenstrom/mortalidade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/terapia
20.
J Cutan Pathol ; 47(9): 850-853, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32335928

RESUMO

Waldenström macroglobulinemia is a lymphoplasmacytic lymphoma with bone marrow involvement and a monoclonal IgM gammopathy. Infiltration of the skin by neoplastic cells is very rare, and it can be difficult to distinguish from marginal zone lymphoma. The MYD88 L265P mutation is strongly associated with Waldenström macroglobulinemia, and it may be helpful in differentiating the two disorders, although the presence of this mutation is not specific, and other factors must be considered when making the final diagnosis. We present a diagnostically challenging case of cutaneous Waldenström macroglobulinemia in which the MYD88 L265P mutation was identified in the skin but not in the bone marrow, due to a low tumor burden.


Assuntos
Fator 88 de Diferenciação Mieloide/genética , Dermatopatias/metabolismo , Macroglobulinemia de Waldenstrom/genética , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Medula Óssea/metabolismo , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina M/sangue , Cadeias kappa de Imunoglobulina/sangue , Linfócitos/metabolismo , Linfócitos/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/patologia , Mutação , Plasmócitos/metabolismo , Plasmócitos/patologia , Rituximab/uso terapêutico , Dermatopatias/patologia , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/patologia
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