Zuna J, Cavé H, Eckert C, Szczepanski T, Meyer C, Mejstrikova E, Fronkova E, Muzikova K, Clappier E, Mendelova D, Boutard P, Schrauder A, Sterba J, Marschalek R, van Dongen J J M, Hrusak O, Stary J, Trka J
CLIP (Childhood Leukaemia Investigation Prague), Department of Paediatric Haematology and Oncology, Charles University, 2nd Medical School, Prague, Czech Republic.
Leukemia. 2007 Jul;21(7):1431-5. doi: 10.1038/sj.leu.2404718. Epub 2007 Apr 26.
Data on secondary acute lymphoblastic leukaemia (sALL) following ALL treatment are very rare. However, the incidence might be underestimated as sALLs without a significant lineage shift might automatically be diagnosed as relapses. Examination of immunoglobulin and T-cell receptor gene rearrangements brought a new tool that can help in discrimination between relapse and sALL. We focused on the recurrences of childhood ALL to discover the real frequency of the sALL after ALL treatment. We compared clonal markers in matched presentation and recurrence samples of 366 patients treated according to the Berlin-Frankfurt-Munster (BFM)-based protocols. We found two cases of sALL and another three, where the recurrence is suspicious of being sALL rather than relapse. Our proposal for the 'secondary ALL after ALL' diagnostic criteria is as follows: (A) No clonal relationship between diagnosis and recurrence; (B) significant immunophenotypic shift--significant cytogenetic shift--gain/loss of a fusion gene. For the sALL (A) plus at least one (B) criterion should be fulfilled. With these criteria, the estimated frequency of the sALL after ALL is according to our data 0.5-1.5% of ALL recurrences on BFM-based protocols. Finally, we propose a treatment strategy for the patients with secondary disease.
关于急性淋巴细胞白血病（ALL）治疗后继发性急性淋巴细胞白血病（sALL）的数据非常罕见。然而，由于没有明显谱系转变的sALL可能会自动被诊断为复发，其发病率可能被低估。免疫球蛋白和T细胞受体基因重排检测带来了一种新工具，有助于区分复发和sALL。我们聚焦于儿童ALL的复发情况，以发现ALL治疗后sALL的实际发生率。我们比较了366例按照基于柏林-法兰克福-明斯特（BFM）方案治疗的患者在初诊和复发样本中的克隆标志物。我们发现了2例sALL病例，另外还有3例复发情况疑似为sALL而非复发。我们提出的“ALL治疗后继发性ALL”诊断标准如下：（A）诊断与复发之间无克隆关系；（B）显著的免疫表型转变——显著的细胞遗传学转变——融合基因的获得/缺失。对于sALL，应满足（A）加至少一项（B）标准。根据这些标准，基于我们的数据，在基于BFM方案的ALL复发中，ALL治疗后sALL的估计发生率为0.5 - 1.5%。最后，我们为患有继发性疾病的患者提出了一种治疗策略。
