Waldenstrom巨球蛋白血症(WM)是一种罕见的B细胞起源的惰性淋巴瘤,其特征是单克隆IgM升高,以MYD88L265P突变和CXCR4突变为常见分子改变。B细胞急性淋巴细胞白血病(B-ALL)是临床异质性,以骨髓和淋巴组织中未成熟淋巴细胞的异常增殖和聚集为特征。WM和ALL是B细胞来源的血液系统恶性肿瘤,具有完全不同的临床表现和生物学特征。KMT2D和MECOM突变在ALL中非常罕见,通常表明疾病预后不良。WM和ALL与KMT2D和MECOM突变的共存尚未见报道。
一名74岁女性患者于2018年7月被诊断为WM,并接受了硼替佐米和地塞米松的四个周期化疗。2018年11月,她接受了免疫调节剂沙利度胺作为维持治疗。2020年11月,布鲁顿的酪氨酸激酶抑制剂(BTKi)被引入中国市场,她以每天80毫克的剂量口服扎努布替尼。该疾病仍处于缓解状态。2021年12月,她出现了全身多个肿大的淋巴结。骨髓和下一代测序(NGS)表明WM和B-ALL与KMT2D和MECOM突变共存。患者接受扎努布替尼联合长春新碱和地塞米松治疗,之后,她出现了严重的骨髓抑制和败血症。病人终于得到了缓解。由于患者的年龄和不良状态,她拒绝静脉化疗,目前正在接受扎努布替尼治疗.
WM和B-ALL的共存非常罕见,尚未有报道。KMT2D和MECOM突变的存在预示着预后不良和对常规治疗方案不敏感的可能性。BTKi通过抑制BTK激活和阻断B细胞肿瘤的一系列恶性转化来实现其抗肿瘤作用。此外,它还作用于T细胞免疫和肿瘤微环境。基于BTKi的联合治疗可以改善该患者的预后。
Waldenstrom Macroglobulinemia (WM) is a rare and indolent lymphoma of B-cell origin characterized by elevated monoclonal IgM, with MYD88L265P mutation and CXCR4 mutation as common molecular alterations. B-cell Acute Lymphoblastic Leukemia (B-ALL) is clinically heterogeneous, characterized by abnormal proliferation and aggregation of immature lymphocytes in the bone marrow and lymphoid tissue. WM and ALL are hematologic malignancies of B-cell origin with completely different clinical manifestations and biological features. KMT2D and
MECOM mutations are very rare in ALL and usually indicate poor disease prognosis. The coexistence of WM and ALL with KMT2D and
MECOM mutations have not been reported.
A 74-year-old female patient was diagnosed with WM in July 2018 and received four cycles of chemotherapy of bortezomib and dexamethasone. In November 2018, she received immunomodulator thalidomide as maintenance therapy. In November 2020, Bruton\'s Tyrosine Kinase inhibitors (BTKi) has been introduced into the Chinese market and she took zanubrutinib orally at a dose of 80 mg per day. The disease remained in remission. In December 2021, she presented with multiple enlarged lymph nodes throughout the body. Bone marrow and next-generation sequencing (NGS) suggested the coexistence of WM and B-ALL with KMT2D and
MECOM mutations. The patient was treated with zanubrutinib in combination with vincristine and dexamethasone, after which she developed severe myelosuppression and septicemia. The patient finally got remission. Due to the patient\'s age and poor status, she refused intravenous chemotherapy and is currently treated with zanubrutinib.
The coexistence of WM and B-ALL is very rare and has not been reported. The presence of both KMT2D and
MECOM mutations predicts a poor prognosis and the possibility of insensitivity to conventional treatment options. BTKi achieves its anti-tumor effects by inhibiting BTK activation and blocking a series of malignant transformations in B-cell tumors. In addition, it also acts on T-cell immunity and tumor microenvironment. Combination therapy based on BTKi may improve the prognosis of this patient.