Fronkova E, Mejstrikova E, Avigad S, Chik K W, Castillo L, Manor S, Reznickova L, Valova T, Zdrahalova K, Hrusak O, Jabali Y, Schrappe M, Conter V, Izraeli S, Li C K, Stark B, Stary J, Trka J
Department of Pediatric Hematology and Oncology, CLIP, Second Medical School, Charles University and University Hospital Motol, Prague, Czech Republic.
Leukemia. 2008 May;22(5):989-97. doi: 10.1038/leu.2008.22. Epub 2008 Feb 28.
The ALL IC-BFM 2002 protocol was created as an alternative to the MRD-based AIEOP-BFM ALL 2000 study, to integrate early response criteria into risk-group stratification in countries not performing routine PCR-based MRD testing. ALL IC stratification comprises the response to prednisone, bone marrow (BM) morphology at days 15 and 33, age, WBC and BCR/ABL or MLL/AF4 presence. Here, we compared this stratification to the MRD-based criteria using MRD evaluation in 163 patients from four ALL IC member countries at days 8, 15 and 33 and week 12. MRD negativity at day 33 was associated with an age of 1-5 years, WBC<20,000 microl(-1), non-T immunophenotype, good prednisone response and non-M3 morphology at day 15. There were no significant associations with gender or hyperdiploidy in the study group, or with TEL/AML1 fusion within BCP-ALL. Patients with M1/2 BM at day 8 tended to be MRD negative at week 12. Patients stratified into the standard-risk group had a better response than intermediate-risk group patients. However, 34% of them were MRD positive at day 33 and/or week 12. Our findings revealed that morphology-based ALL IC risk-group stratification allows the identification of most MRD high-risk patients, but fails to discriminate the MRD low-risk group assigned to therapy reduction.
ALL IC - BFM 2002方案是作为基于微小残留病（MRD）的AIEOP - BFM ALL 2000研究的替代方案而制定的，目的是在未进行常规基于聚合酶链反应（PCR）的MRD检测的国家，将早期反应标准纳入风险组分层。ALL IC分层包括对泼尼松的反应、第15天和第33天的骨髓（BM）形态、年龄、白细胞计数以及BCR/ABL或MLL/AF4的存在情况。在此，我们在来自四个ALL IC成员国的163例患者中，于第8天、第15天、第33天和第12周使用MRD评估，将这种分层与基于MRD的标准进行了比较。第33天的MRD阴性与年龄1 - 5岁、白细胞计数<20,000/微升、非T免疫表型、泼尼松反应良好以及第15天的非M3形态相关。在研究组中，与性别、超二倍体或BCP - ALL内的TEL/AML1融合均无显著关联。第8天BM为M1/2的患者在第12周往往MRD阴性。分层为标准风险组的患者比中风险组患者反应更好。然而，其中34%的患者在第33天和/或第12周MRD呈阳性。我们的研究结果表明，基于形态学的ALL IC风险组分层能够识别出大多数MRD高危患者，但无法区分被分配到治疗减量组的MRD低危组。
