Ranta Susanna, Nilsson Frans, Harila-Saari Arja, Saft Leonie, Tani Edneia, Söderhäll Stefan, Porwit Anna, Hultdin Magnus, Noren-Nyström Ulrika, Heyman Mats
Childhood Cancer Research Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
Pediatr Blood Cancer. 2015 Jun;62(6):951-6. doi: 10.1002/pbc.25363. Epub 2014 Dec 24.
Therapy directed at the central nervous system (CNS) is an essential part of the treatment for childhood acute lymphoblastic leukemia (ALL). The current evaluation of CNS involvement based on cytomorphological examination of the cerebrospinal fluid (CSF) alone is not as sensitive with low cell counts as flow cytometric immunophenotyping (FCI) of the CSF. However, the importance of low CSF blasts counts at diagnosis is uncertain. We sought to determine the significance of FCI in relation to conventional morphological examination.
We retrospectively compared FCI of the CSF with cytomorphology at diagnosis or relapse of childhood ALL. All patients were diagnosed 2000-2012 in Stockholm or Umeå, Sweden. Clinical data were collected from medical records and the Nordic leukemia registry. Treatment assignment was based on morphological examination only.
The cohort was comprised of 214 patients with ALL. CSF involvement was detected by both methods in 20 patients, in 17 by FCI alone, and in one patient by cytomorphology alone. The relapse rate was higher for patients with negative cytology but positive FCI compared to those without CNS involvement using both methods. The difference was especially marked in the current protocol. However, none of the patients with negative CSF cytology but positive FCI had a CNS relapse.
FCI of the CSF increased the detection rate of CNS involvement of ALL approximately two times compared to cytomorphology. Patients with low-level CNS involvement may benefit from additional intensified systemic or CNS-directed therapy, but larger studies are needed.
针对中枢神经系统(CNS)的治疗是儿童急性淋巴细胞白血病(ALL)治疗的重要组成部分。目前仅基于脑脊液(CSF)细胞形态学检查对CNS受累情况进行评估,在细胞计数较低时不如CSF流式细胞免疫表型分析(FCI)敏感。然而,诊断时CSF原始细胞计数较低的重要性尚不确定。我们试图确定FCI相对于传统形态学检查的意义。
我们回顾性比较了儿童ALL诊断或复发时CSF的FCI与细胞形态学。所有患者于2000年至2012年在瑞典斯德哥尔摩或于默奥被诊断。临床数据从病历和北欧白血病登记处收集。治疗分配仅基于形态学检查。
该队列包括214例ALL患者。两种方法均检测到20例患者的CSF受累,仅FCI检测到17例,仅细胞形态学检测到1例。与两种方法均未发现CNS受累的患者相比,细胞学阴性但FCI阳性的患者复发率更高。在当前方案中差异尤为明显。然而,CSF细胞学阴性但FCI阳性的患者均未发生CNS复发。
与细胞形态学相比,CSF的FCI使ALL中枢神经系统受累的检测率提高了约两倍。中枢神经系统低度受累的患者可能从额外的强化全身或中枢定向治疗中获益,但需要更大规模的研究。