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1.
Danka Cholujova Gabor Beke Zachary R. Hunter Teru Hideshima Ludmila Flores Tatiana Zeleznikova Denisa Harrachova Lubos Klucar Merav Leiba Lubos Drgona Steven P. Treon Efstathios Kastritis David M. Dorfman Kenneth C. Anderson Jana Jakubikova 《International journal of cancer. Journal international du cancer》2023,152(9):1947-1963
Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In-depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD-1/PD-L1&PD-L2, TIGIT/PVR, CD137/CD137-L, CTLA-4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies. 相似文献
2.
Naohiro Sekiguchi Shinya Rai Wataru Munakata Kenshi Suzuki Hiroshi Handa Hirohiko Shibayama Tomoyuki Endo Yasuhito Terui Noriko Iwaki Noriko Fukuhara Hiro Tatetsu Shinsuke Iida Takayuki Ishikawa Ryota Shiibashi Koji Izutsu 《Cancer science》2020,111(9):3327-3337
Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646). 相似文献
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Andrew N. Minzenmayer Roberto N. Miranda Priscilla R. Powell Palak K. Parekh 《Journal of cutaneous pathology》2020,47(9):850-853
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. 相似文献
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6.
Nobuki Maki Toshio Demitsu Naoka Umemoto Kazutaka Nagashima Toshinobu Nakamura Maki Kakurai Satoshi Nakamura Tomoko Yamada Norito Ishii Takashi Hashimoto 《The Journal of dermatology》2016,43(5):571-574
A 61‐year‐old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl‐split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme‐linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M‐proteinemia of IgM‐κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C‐terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti‐BP180 C‐terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris. 相似文献
7.
《Neurocirugía (Asturias, Spain)》2022,33(5):250-253
The differential diagnosis of bilateral lower extremity weakness is broad. We present a very rare case of a 48-year old male patient, with walking difficulties due to Bing–Neel syndrome. On clinical examination, there was a significant loss of muscle power in all his lower extremities key-muscle groups. The lumbar spine magnetic resonance imaging (MRI) showed only mild degenerative changes, whereas the MRI of the head indicated a diffuse meningeal thickening at the right temporal region, characterized by significant enhancement after contrast administration. Serum protein electrophoresis detected an IgM-kappa monoclonal protein. The patient received intrathecal chemotherapy with methotrexate and cytarabine, and was started on oral ibrutinib 420 mg daily. In conclusion, a past medical history of Waldenstrom macroglobulinemia in conjunction with neurological manifestations should alert the treating physician for Bing–Neel syndrome. A complete diagnostic imaging and serologic protocol helps in setting the final diagnosis. Steroids are part of the treatment, but should be given after the diagnosis is set. Neurosurgical intervention is indicated for histologic confirmation in the case of diagnostic uncertainty. 相似文献
8.
淋巴浆细胞淋巴瘤/华氏巨球蛋白血症(LPL/WM)是少见的非霍奇金淋巴瘤,以淋巴浆细胞增生引起血清单克隆IgM增高为特点,通常累及骨髓、淋巴结、脾脏,其发病率较低,不易诊断。该文报道1例以冷凝集素综合征为首发表现的LPL/WM,行骨髓活组织病理学检查(活检)、血清免疫固定电泳、流式细胞学检验明确诊断,确诊后仅接受TD (沙利度胺、地塞米松)方案治疗。经治疗后患者病情好转,随访情况稳定。临床上对于疑为LPL/WM的患者,应尽快行骨髓活检、血清免疫固定电泳、流式细胞学检验等以尽早确诊,确诊后应根据患者病情选择适合的个体化治疗方案。 相似文献
9.
Patrick Eulitt Denise Fabian Crystal Kelly Jessica Hemminger Basem M. William 《Hematology/oncology and stem cell therapy》2019,12(1):54-59
Waldenström’s macroglobulinemia is a rare hematology malignancy which often presents with “B symptoms,” anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström’s macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström’s macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis. 相似文献
10.
Sevgi Kalayoglu-Besisik 《Transfusion and apheresis science》2018,57(1):35-39
Hyperviscosity syndrome (HVS) develops most commonly in Waldenström's macroglobulinemia (WM) and multiple myeloma (MM). Plasmapheresis is the immediate therapy and very effective at relieving symptoms by removing paraprotein. The most commonly used replacement fluid is 4%–5% human albumin in physiologic saline. FFP may be used in patients with coagulation abnormalities. Plasmapheresis should be continued until acute symptoms abate. Hyperviscosity impairs the circulation in the retina and causes hemorrhages around the small retinal vessels. Early diagnosis and urgent plasmapheresis may reduce blindness caused by retinal hemorrhages and/or retinal detachment. In HCV related mixed cryoglobulinemias, plasmapheresis is indicated if rapidly evolving life-threatening disease with immunosuppressive agent exists. In non-infectious mixed cryoglobulinemia plasmapheresis is indicated when the disease manifestations are severe, as a second line option. In WM patients with hyperviscosity symptoms and IgM?>?4?g/dL, preemptive plasmapheresis is recommended to prevent an IgM flare with rituximab. Certain IgG/A MGUS-associated neuropathy patients may benefit from plasmapheresis. For cast nephropathy (suspected or biopsy proven), plasmapheresis is recommended when the sFLC?≥?500?mg/l and as early as possible (<1 month with kidney injury). Theoretically, extracorporeal removal alone, without efficient tumor killing, could not reduce sFLC due to high production by the tumor mass and rapid rebound between compartments. 相似文献