Perkins Joanna L, Harris Anne, Pozos Tamara C
*Children's Cancer and Blood Disorders Program, Children's Hospitals and Clinics of Minnesota †Pediatric Infectious Diseases and Immunology, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN.
J Pediatr Hematol Oncol. 2017 Jan;39(1):1-5. doi: 10.1097/MPH.0000000000000697.
Children with leukemia suffer immune dysfunction from their malignancy and chemotherapy. The immune system components most affected, the degree to which immune suppression occurs, and the duration of immunodeficiency are incompletely characterized. This study measures immunologic parameters following completion of therapy.
This is a prospective, single institution cohort study. Eligible children with acute myelogenous or acute lymphoblastic leukemia diagnosed between 1 and 21 years of age were enrolled at therapy completion. Immune parameters were assessed at the end of therapy and 6 months later: complete blood counts, immunoglobulin levels, quantitative lymphocyte subsets, mitogen-induced lymphocyte proliferation, natural killer cell function, and vaccine titers.
Twenty patients were evaluated; 13 (65%) were female, 15 had acute lymphoblastic leukemia (75%). Mean age at diagnosis was 7.9 years. At end of therapy, all patients had some degree of immune dysfunction. At 6 months posttherapy, persistent abnormalities included: leukopenia (25%), neutropenia (15%), lymphopenia (5%), hypogammaglobulinemia (25%), one or more subtherapeutic vaccine titers (100%), abnormal lymphocyte subset levels (20%), decreased (15%), or absent (10%) natural killer cell function and abnormal lymphocyte proliferative responses (25%).
All patients had multiple abnormalities at end of therapy, and all patients had some degree of persistent immune dysfunction at 6 months after completion of therapy. Clinical implications of these laboratory abnormalities are currently unknown; longer term evaluations are ongoing. We demonstrate that survivors of childhood cancer have lasting quantitative and functional immunologic defects and may remain at risk for infectious complications after completion of therapy.
白血病患儿因恶性肿瘤和化疗而出现免疫功能障碍。免疫系统受影响最严重的组成部分、免疫抑制发生的程度以及免疫缺陷的持续时间尚未完全明确。本研究在治疗结束后测量免疫参数。
这是一项前瞻性、单机构队列研究。年龄在1至21岁之间、确诊为急性髓性白血病或急性淋巴细胞白血病的符合条件的患儿在治疗结束时入组。在治疗结束时和6个月后评估免疫参数:全血细胞计数、免疫球蛋白水平、定量淋巴细胞亚群、丝裂原诱导的淋巴细胞增殖、自然杀伤细胞功能和疫苗滴度。
对20例患者进行了评估;13例(65%)为女性,15例患有急性淋巴细胞白血病(75%)。诊断时的平均年龄为7.9岁。治疗结束时,所有患者均有一定程度的免疫功能障碍。治疗后6个月,持续异常包括:白细胞减少(25%)、中性粒细胞减少(15%)、淋巴细胞减少(5%)、低丙种球蛋白血症(25%)、一种或多种疫苗滴度低于治疗水平(100%)、淋巴细胞亚群水平异常(20%)、自然杀伤细胞功能降低(15%)或缺失(10%)以及淋巴细胞增殖反应异常(25%)。
所有患者在治疗结束时均有多种异常,并且在治疗完成6个月时所有患者均有一定程度的持续免疫功能障碍。这些实验室异常的临床意义目前尚不清楚;正在进行长期评估。我们证明儿童癌症幸存者存在持久的定量和功能性免疫缺陷,并且在治疗完成后可能仍有感染并发症的风险。