CLIP-Childhood Leukemia Investigation Prague Department of Pediatric Hematology and Oncology, Charles University, 2ndFaculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Haematologica. 2010 Jun;95(6):928-35. doi: 10.3324/haematol.2009.014506. Epub 2010 Feb 9.
Mixed phenotype acute leukemia (MPAL) represents a diagnostic and therapeutic dilemma. The European Group for the Immunological Classification of Leukemias (EGIL) scoring system unambiguously defines MPAL expressing aberrant lineage markers. Discussions surrounding it have focused on scoring details, and information is limited regarding its biological, clinical and prognostic significance. The recent World Health Organization classification is simpler and could replace the EGIL scoring system after transformation into unambiguous guidelines.
Simple immunophenotypic criteria were used to classify all cases of childhood acute leukemia in order to provide therapy directed against acute lymphoblastic leukemia or acute myeloid leukemia. Prognosis, genotype and immunoglobulin/T-cell receptor gene rearrangement status were analyzed.
The incidences of MPAL were 28/582 and 4/107 for children treated with acute lymphoblastic leukemia and acute myeloid leukemia regimens, respectively. In immunophenotypic principal component analysis, MPAL treated as T-cell acute lymphoblastic leukemia clustered between cases of non-mixed T-cell acute lymphoblastic leukemia and acute myeloid leukemia, while other MPAL cases were included in the respective non-mixed B-cell progenitor acute lymphoblastic leukemia or acute myeloid leukemia clusters. Analogously, immunoglobulin/T-cell receptor gene rearrangements followed the expected pattern in patients treated as having acute myeloid leukemia (non-rearranged, 4/4) or as having B-cell progenitor acute lymphoblastic leukemia (rearranged, 20/20), but were missing in 3/5 analyzed cases of MPAL treated as having T-cell acute lymphobastic leukemia. In patients who received acute lymphoblastic leukemia treatment, the 5-year event-free survival of the MPAL cases was worse than that of the non-mixed cases (53+/-10% and 76+/-2% at 5 years, respectively, P=0.0075), with a more pronounced difference among B lineage cases. The small numbers of MPAL cases treated as T-cell acute lymphoblastic leukemia or as acute myeloid leukemia hampered separate statistics. We compared prognosis of all subsets with the prognosis of previously published cohorts.
Simple immunophenotypic criteria are useful for therapy decisions in MPAL. In B lineage leukemia, MPAL confers poorer prognosis. However, our data do not justify a preferential use of current acute myeloid leukemia-based therapy in MPAL.
混合表型急性白血病（MPAL）代表了一种诊断和治疗上的困境。欧洲白血病免疫学分型组（EGIL）评分系统明确定义了表达异常谱系标志物的 MPAL。围绕该系统的讨论集中在评分细节上，关于其生物学、临床和预后意义的信息有限。最近的世界卫生组织分类更为简单，在转化为明确的指南后可能会取代 EGIL 评分系统。
简单的免疫表型标准用于对所有儿童急性白血病病例进行分类，以便提供针对急性淋巴细胞白血病或急性髓系白血病的治疗。分析了预后、基因型和免疫球蛋白/T 细胞受体基因重排状态。
在接受急性淋巴细胞白血病和急性髓系白血病方案治疗的儿童中，MPAL 的发生率分别为 28/582 和 4/107。在免疫表型主成分分析中，MPAL 作为 T 细胞急性淋巴细胞白血病治疗时聚类在非混合 T 细胞急性淋巴细胞白血病和急性髓系白血病之间，而其他 MPAL 病例则归入各自的非混合 B 细胞祖细胞急性淋巴细胞白血病或急性髓系白血病聚类中。类似地，在接受急性髓系白血病（未重排，4/4）或 B 细胞祖细胞急性淋巴细胞白血病（重排，20/20）治疗的患者中，免疫球蛋白/T 细胞受体基因重排遵循预期模式，但在 5 例接受 T 细胞急性淋巴细胞白血病治疗的 MPAL 分析病例中缺失。在接受急性淋巴细胞白血病治疗的患者中，MPAL 病例的 5 年无事件生存率比非混合病例差（5 年分别为 53+/-10%和 76+/-2%，P=0.0075），B 细胞谱系病例的差异更为明显。接受 T 细胞急性淋巴细胞白血病或急性髓系白血病治疗的 MPAL 病例数量较少，阻碍了单独的统计分析。我们将所有亚组的预后与以前发表的队列的预后进行了比较。
简单的免疫表型标准可用于 MPAL 的治疗决策。在 B 细胞谱系白血病中，MPAL 预后较差。然而，我们的数据并不支持在 MPAL 中优先使用目前基于急性髓系白血病的治疗方法。
