Zuna Jan, Hovorkova Lenka, Krotka Justina, Koehrmann Amelie, Bardini Michela, Winkowska Lucie, Fronkova Eva, Alten Julia, Koehler Rolf, Eckert Cornelia, Brizzolara Lisa, Trkova Marie, Stuchly Jan, Zimmermann Martin, De Lorenzo Paola, Valsecchi Maria Grazia, Conter Valentino, Stary Jan, Schrappe Martin, Biondi Andrea, Trka Jan, Zaliova Marketa, Cazzaniga Giovanni, Cario Gunnar
CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Leukemia. 2022 Dec;36(12):2793-2801. doi: 10.1038/s41375-022-01668-0. Epub 2022 Aug 6.
Recently, we defined "CML-like" subtype of BCR::ABL1-positive acute lymphoblastic leukemia (ALL), resembling lymphoid blast crisis of chronic myeloid leukemia (CML). Here we retrospectively analyzed prognostic relevance of minimal residual disease (MRD) and other features in 147 children with BCR::ABL1-positive ALL (diagnosed I/2000-IV/2021, treated according to EsPhALL (n = 133) or other (n = 14) protocols), using DNA-based monitoring of BCR::ABL1 genomic breakpoint and clonal immunoglobulin/T-cell receptor gene rearrangements. Although overall prognosis of CML-like (n = 48) and typical ALL (n = 99) was similar (5-year-EFS 60% and 49%, respectively; 5-year-OS 75% and 73%, respectively), typical ALL presented more relapses while CML-like patients more often died in the first remission. Prognostic role of MRD was significant in the typical ALL (p = 0.0005 in multivariate analysis for EFS). In contrast, in CML-like patients MRD was not significant (p values > 0.2) and inapplicable for therapy adjustment. Moreover, in the typical ALL, risk-prediction could be further improved by considering initial hyperleukocytosis. Early distinguishing typical BCR::ABL1-positive ALL and CML-like patients is essential to enable optimal treatment approach in upcoming protocols. For the typical ALL, tyrosine-kinase inhibitors and concurrent chemotherapy with risk-directed intensity should be recommended; in the CML-like disease, no relevant prognostic feature applicable for therapy tailoring was found so far.
最近，我们定义了BCR::ABL1阳性急性淋巴细胞白血病（ALL）的“CML样”亚型，其类似于慢性粒细胞白血病（CML）的淋巴细胞母细胞危象。在此，我们回顾性分析了147例BCR::ABL1阳性ALL患儿（2000年1月至2021年4月诊断，根据EsPhALL方案（n = 133）或其他方案（n = 14）治疗）微小残留病（MRD）及其他特征的预后相关性，采用基于DNA的BCR::ABL1基因组断点监测及克隆性免疫球蛋白/T细胞受体基因重排。尽管CML样ALL（n = 48）和典型ALL（n = 99）的总体预后相似（5年无事件生存率分别为60%和49%；5年总生存率分别为75%和73%），但典型ALL复发更多，而CML样ALL患者更多在首次缓解期死亡。MRD的预后作用在典型ALL中具有显著性（无事件生存率多因素分析中p = 0.0005）。相比之下，在CML样ALL患者中MRD无显著性（p值> 0.2）且不适用于治疗调整。此外，在典型ALL中，考虑初始高白细胞血症可进一步改善风险预测。早期区分典型BCR::ABL1阳性ALL和CML样ALL患者对于在未来方案中采用最佳治疗方法至关重要。对于典型ALL，应推荐酪氨酸激酶抑制剂及风险导向强度的联合化疗；在CML样疾病中，目前尚未发现适用于治疗调整的相关预后特征。
