Mussolin Lara, Damm-Welk Christine, Pillon Marta, Woessmann Wilhelm
Department of Women's and Children's Health, Clinic of Pediatric Hemato-Oncology, University of Padova, 35128 Padova, Italy.
Istituto di Ricerca Pediatrica, Fondazione Cittàdella Speranza, 35127 Padova, Italy.
Cancers (Basel). 2021 Apr 15;13(8):1907. doi: 10.3390/cancers13081907.
Minimal residual disease (MRD) detection is established routine practice for treatment stratification in leukemia and used for treatment optimization in adult lymphomas. Minimal disease studies in childhood non-Hodgkin lymphomas are challenged by stratified treatment in different subtypes, high cure rates, low patient numbers, limited initial tumor material, and early progression. Current clinical applications differ between the subtypes. A prognostic value of minimal disseminated disease (MDD) could not yet be clearly established for lymphoblastic lymphoma using flow cytometry and PCR-based methods for T-cell receptor (TCR) or immunoglobulin (IG) rearrangements. fusion sequences or IG rearrangements enable minimal disease detection in Burkitt lymphoma and -leukemia. An additional prognostic value of MDD in Burkitt lymphoma and early MRD in Burkitt leukemia is implicated by single studies with risk-adapted therapy. MDD and MRD determined by PCR for ALK-fusion transcripts are independent prognostic parameters for patients with ALK-positive anaplastic large cell lymphoma (ALCL). They are introduced in routine clinical practice and used for patient stratification in clinical studies. Early MRD might serve as an endpoint for clinical trials and for guiding individual therapy. Validation of MDD and MRD as prognostic parameters is required for all subtypes but ALCL. Next-generation sequencing-based methods may provide new options and applications for minimal disease evaluation in childhood lymphomas.
微小残留病（MRD）检测是白血病治疗分层的常规做法，并用于成人淋巴瘤的治疗优化。儿童非霍奇金淋巴瘤的微小疾病研究面临不同亚型的分层治疗、高治愈率、患者数量少、初始肿瘤材料有限以及早期进展等挑战。目前不同亚型的临床应用存在差异。对于淋巴母细胞淋巴瘤，使用流式细胞术和基于聚合酶链反应（PCR）的T细胞受体（TCR）或免疫球蛋白（IG）重排方法，尚未明确确立微小播散性疾病（MDD）的预后价值。融合序列或IG重排能够检测伯基特淋巴瘤和伯基特白血病中的微小疾病。单篇关于风险适应性治疗的研究表明，MDD在伯基特淋巴瘤中的额外预后价值以及伯基特白血病中的早期MRD具有预后意义。通过PCR检测ALK融合转录本确定的MDD和MRD是ALK阳性间变性大细胞淋巴瘤（ALCL）患者的独立预后参数。它们已被引入常规临床实践，并用于临床研究中的患者分层。早期MRD可能作为临床试验的终点并指导个体化治疗。除了ALCL外，所有亚型都需要验证MDD和MRD作为预后参数。基于下一代测序技术的方法可能为儿童淋巴瘤的微小疾病评估提供新的选择和应用。
