滤泡性淋巴瘤序贯转化B淋母细胞白血病和弥漫大B细胞淋巴瘤1例并文献复习

Histologic transformation from follicular lymphoma to B-lymphoblastic leukemia and diffuse large B-cell lymphoma:A case report and literature review

目的:报道1例在滤泡淋巴瘤(follicular lymphoma,FL)基础上序贯向B淋母细胞白血病/淋巴瘤(B-ALL)和弥漫大B细胞淋巴瘤(DLBCL)转化的特殊病例,以提高对该类疾病的认识,为其诊疗提供临床经验。方法:回顾性分析本例患者的临床资料和诊治过程,并复习自PubMed和CNKI检索到的病例。结果:患者,男,47岁,经淋巴结活检病理检查诊断FL 2级,分期为IV期。常规6疗程BR方案化疗达完全缓解(CR),诊断后6个月疾病进展为B-ALL。本例患者经靶向CD19嵌合抗原受体修饰T细胞疗法(CAR-T)治疗达CR,缓解期持续1年,其后发现腹腔淋巴结增大,经活检证实为DLBCL。3例标本中均检测到特征性t(14;18)易位,推测其具有克隆同源性;B-ALL标本中MYC重排为阳性,结合显著基因学异常,可能促进了FL向淋母侵袭性转化。这种转化非常少见,目前国内外累积仅报道20余例患者,疾病进展迅速,生存期常不足半年。大部分类似病例都具有MYC重排,提示MYC重排可能是FL向B-ALL转化的关键遗传学基础。结论:FL可以组织学转化为B-ALL,MYC重排可能是其发生的关键遗传学基础。CAR-T疗法有望取得较为理想的疗效,仍需要新的方法维持长期疗效。

Objective:We presented a rare clinical case of follicular lymphoma(FL),which sequentially transformed into B-lymphoblastic leukemia(B-ALL)and diffuse large B-cell lymphoma(DLBCL),with the aim of raising the awareness of the rare occurrence of transformation and providing clinical experience for treatment.Methods:The clinical process of diagnosis and treatment of this patient were retrospectively analyzed.The related literature of PubMed and CNKI were searched and reviewed.Results:The patient was a 47-year-old male diagnosed with FL,grade 2 stage IV,based on an excisional biopsy of en enlarged right inguinal lymph node.He was given BR(rituximab,bendamustine)regimen and achieved complete remission(CR)after 6 cycles of treatment.He transformed into B-ALL roughly 6 months after the initial diagnosis.In our case,the patient was successfully treated with CD19-targed chimeric antigen receptor modified T-cell(CAR-T)therapy and maintained disease-free survival within the following year,until progressed with a abdominal mass diagnosed with DLBCL.Cytogenetically,an identical t(14;18)translocation was shared by FL,B-ALL and DLBCL tissues,indicating a clonal relationship between the three type of lymphoma cells.Of note,a MYC gene translocation was specific to the B-ALL stage,together with a marked mutational profile,may have contributed to the lymphoblastic transformation of FL.Transformation of FL into B-lymphoblastic lymphoma/leukemiais rare and approximately 25 similar cases have been reported previously in literature.The MYC translocation is reported in almost all similar cases and likely is crucial in the pathogenesis of the lymphoblastic transformation.Patients with this type of translocation usually have a poor prognosis,and no standard therapy has been established.Conclusion:This case report highlights the possible transformation of FL into precursor B-lymphoblastic lymphoma/leukemia,in which acquisition of MYC gene rearrangement is a critical event.Similar cases should be accumulated and analyzed carefully.CAR-T therapy might be a safe and effective approach,despite further strategies are needed to achieve a durable CR.