Pediatric Hematology and Oncology, University Hospital Schleswig-Holstein, Lübeck Campus, Germany.
Haematologica. 2012 Jul;97(7):1048-56. doi: 10.3324/haematol.2011.047613. Epub 2012 Jan 22.
In the ALL-BFM 95 trial for treatment of acute lymphoblastic leukemia, response to a prednisone pre-phase (prednisone response) was used for risk stratification in combination with age and white blood cell count at diagnosis, response to induction therapy and specific genetic high-risk features.
Cytomorphological marrow response was prospectively assessed on Day 15 during induction, and its prognostic value was analyzed in 1,431 patients treated on ALL-BFM 95.
The 8-year probabilities of event-free survival were 86.1%, 74.5%, and 46.4% for patients with M1, M2, and M3 Day 15 marrows, respectively. Compared to prednisone response, Day 15 marrow response was superior in outcome prediction in precursor B-cell and T-cell leukemia with, however, a differential effect depending on blast lineage. Outcome was poor in T-cell leukemia patients with prednisone poor-response independent of Day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by Day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B-cell leukemia when stratified by Day 15 marrow response. Age and white blood cell count retained their independent prognostic effect.
Selective addition of Day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 (currently in use in several countries as regular chemotherapy protocol for childhood acute lymphoblastic leukemia) may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries that lack the technical and/or financial resources associated with the application of minimal residual disease analysis.
在 ALL-BFM 95 急性淋巴细胞白血病治疗试验中，泼尼松预治疗期（泼尼松反应）与年龄和诊断时的白细胞计数、诱导治疗反应以及特定的遗传高危特征相结合，用于风险分层。
在诱导期的第 15 天，前瞻性评估细胞形态学骨髓反应，在接受 ALL-BFM 95 治疗的 1431 例患者中分析其预后价值。
M1、M2 和 M3 第 15 天骨髓的患者 8 年无事件生存概率分别为 86.1%、74.5%和 46.4%。与泼尼松反应相比，前体 B 细胞和 T 细胞白血病的第 15 天骨髓反应在预后预测方面更具优势，但因白血病细胞谱系而异。T 细胞白血病患者即使泼尼松反应不佳，也与第 15 天骨髓反应无关，而泼尼松反应良好的患者中，通过第 15 天骨髓反应可确定不同的风险组。相比之下，当按第 15 天骨髓反应分层时，泼尼松反应在前体 B 细胞白血病中失去了预后意义。年龄和白细胞计数保留了其独立的预后作用。
在 ALL-BFM 95 上应用的常规分层标准中，选择性添加第 15 天骨髓反应（目前在几个国家作为儿童急性淋巴细胞白血病的常规化疗方案使用）可能会显著改善风险适应治疗。尽管前沿试验的风险分层目前主要由微小残留病评估主导，但这里提出的改进常规风险评估对于缺乏微小残留病分析相关技术和/或资金资源的国家可能具有重要意义。
