Zuna Jan, Moericke Anja, Arens Mari, Koehler Rolf, Panzer-Grümayer Renate, Bartram Claus R, Fischer Susanna, Fronkova Eva, Zaliova Marketa, Schrauder André, Stanulla Martin, Zimmermann Martin, Trka Jan, Stary Jan, Attarbaschi Andishe, Mann Georg, Schrappe Martin, Cario Gunnar
CLIP, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic.
Department of Paediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Br J Haematol. 2016 Jun;173(5):742-8. doi: 10.1111/bjh.13989. Epub 2016 Feb 23.
Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration (n = 50) had a worse 5-year event-free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment.
诱导治疗结束时的微小残留病（MRD）对于急性淋巴细胞白血病（ALL）的风险分层很重要，但骨髓穿刺检查常常被推迟或必须重复进行，以满足血液学缓解形态学评估和/或MRD分析的定性和定量标准。目前尚不清楚骨髓穿刺延迟对所测MRD水平及由此产生的风险分层的影响。我们分析了289例需要重复进行骨髓穿刺的小儿ALL患者的配对MRD数据。108例患者（37%）的MRD水平存在差异，其中大多数（85/108）有所下降。应用2000年ALL-柏林-法兰克福-明斯特标准时，这将导致289例患者中的64例（23%）被分配到不同的风险组。MRD变化与延迟时间有关；延迟≥7天的患者中有40%的MRD水平降至更低，而延迟较短的患者中这一比例仅为18%。初诊时MRD阳性但重复骨髓穿刺时MRD阴性的患者（n = 50）的5年无事件生存率低于初诊时即为阴性的患者（n = 115）（86± 5%对94±2%；P = 0·024）。我们得出结论，应按照方案计划如期进行骨髓穿刺检查，因为诱导治疗结束时延迟进行MRD采样可能会导致MRD负荷假低，并扭曲基于MRD的风险评估。
