Pawińska-Wasikowska Katarzyna, Balwierz Walentyna
Oddział Onkologii i Hematologii Dzieciecej, Uniwersytecki Szpital Dzieciecy w Krakowie, Kraków.
Przegl Lek. 2010;67(6):361-5.
Leukemias are the most common malignancy in children, and acute lymphoblastic leukemia (ALL) accounts for 85% of all childhood leukemias. Sequential monitoring of MRD (minimal residual disease) in a set time points during the induction therapy in ALL proves to be a powerful and independent predictor of treatment outcome. Crucial limitation of MRD monitoring by flow cytometry is immunophenotypic changes seen at relapse. Up to now there are single publications about immunophenotypic changes during treatment of ALL in children. Objective was to assess changes in expression of cell antigens during induction treatment of ALL. From May 2005 to January 2008, from among 78 patients with ALL treated in Oncology and Hematology Department, Children's University Hospital in Krakow according to international treatment protocol ALL IC-BFM-2002, 42 were enrolled in assessment of antigens' cells modulation expression during induction. Finally, 24 boys and 18 girls were eligible for evaluation. For MRD detection 4-colour flow cytometry with FACS Diva Software v.5.1 (BD Immunocytometry Systems) was used. The panel of monoclonal antibodies used for MRD detection was based on ALL IC-BFM-2002 standard, modified by additional antibodies combinations from ALL-BFM-2000 protocol. Identification of leukemia associated phenotype (LAP), used for cell analysis in sequential time points, with a set monoclonal antibodies panel, was possible in all analyzed patients. Superficial and cytoplasmic antigens modulation was observed in most of the patients during MRD monitoring. Changes of antigens were seen mostly in PB on day 8 and on day 15 both in PB and BM. The most common antigen modulation found in children with cALL was: downmodulation of CD10, CD34, CD19, and upmodulation of CD45, CD11a, CD20. Unequivocal character of modulation of CD66c, CD58, CD38 was difficult to define (up and downmodulation). Introduction of treatment monitoring based on flow cytometry MRD measurement could lead to further individualization of therapy and improovement of cure rates in ALL, as well as to reducing side effects of ALL treatment and decrease total cost of patient therapy.
白血病是儿童最常见的恶性肿瘤,急性淋巴细胞白血病(ALL)占所有儿童白血病的85%。在ALL诱导治疗期间的特定时间点对微小残留病(MRD)进行连续监测被证明是治疗结果的有力且独立的预测指标。流式细胞术监测MRD的关键局限性在于复发时出现的免疫表型变化。到目前为止,有关于儿童ALL治疗期间免疫表型变化的单篇报道。目的是评估ALL诱导治疗期间细胞抗原表达的变化。2005年5月至2008年1月,在克拉科夫儿童医院肿瘤血液科按照国际治疗方案ALL IC-BFM-2002治疗的78例ALL患者中,42例被纳入诱导期间抗原细胞调节表达的评估。最终,24名男孩和18名女孩符合评估条件。使用配备FACS Diva Software v.5.1(BD免疫细胞仪系统)的四色流式细胞术进行MRD检测。用于MRD检测的单克隆抗体组合基于ALL IC-BFM-2002标准,并通过ALL-BFM-2000方案中的额外抗体组合进行了修改。在所有分析的患者中,使用一组单克隆抗体组合在连续时间点对白血病相关表型(LAP)进行细胞分析是可行的。在MRD监测期间,大多数患者观察到表面和细胞质抗原的调节。抗原变化主要见于第8天的外周血以及第15天的外周血和骨髓。在cALL儿童中发现的最常见抗原调节为:CD10、CD34、CD19下调,CD45、CD11a、CD20上调。CD66c、CD58、CD38调节的明确特征难以界定(上调和下调)。基于流式细胞术MRD测量引入治疗监测可能会导致ALL治疗的进一步个体化、提高治愈率,同时减少ALL治疗的副作用并降低患者治疗的总成本。