比较儿童和青年急性淋巴细胞白血病治疗后发生骨坏死的临床表型、时间和危险因素。

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia.

机构信息

Department of Pediatrics and Adolescent Medicine, the Juliane Marie Center, University Hospital Rigshospitalet, Copenhagen, Denmark.

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

出版信息

Pediatr Blood Cancer. 2018 Oct;65(10):e27300. doi: 10.1002/pbc.27300. Epub 2018 Jun 26.

DOI:10.1002/pbc.27300

PMID:29943905

Abstract

BACKGROUND

Treatment-related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL).

PROCEDURE

This study included 1,489 patients with ALL, aged 1-45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate-week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults.

RESULTS

ON was diagnosed in 67 patients, yielding a 5-year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple-joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0-9.9 years (0.7 years [range: 0.2-2.1]) compared with adolescents (1.8 years [range: 0.3-3.7, P < 0.001]) and adults (2.1 years [range: 0.4-5.3, P = 0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.1-4.2) but not in children aged 1.1-9.9 years (HR = 2.4, 95% CI: 0.9-6.2, P = 0.08) or adults aged 19-45 years (HR = 1.1, 95% CI: 0.3-4.0). Age above 10 years at ALL diagnosis (odds ratio [OR] = 3.7, P = 0.026) and multiple joints affected at ON diagnosis (OR = 3.4, P = 0.027) were risk factors for developing severe ON.

CONCLUSION

We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.

摘要

背景

治疗相关的骨坏死（ON）是急性淋巴细胞白血病（ALL）治疗的严重并发症。

方法

本研究纳入了 1489 例年龄为 1-45 岁的 ALL 患者，按照北欧儿科血液学和肿瘤学协会 ALL2008 方案治疗，在延迟强化阶段每两周使用一次地塞米松，前瞻性登记有症状的 ON。我们旨在比较儿童和青少年中 ON 的危险因素、发病时间和临床特征。

结果

67 例患者诊断为 ON，5 年累积发生率为 6.3%，但女性青少年中为 28%。ALL 诊断时的中位年龄分别为 12.1 岁和 14.9 岁（女性和男性）。在 ON 诊断时，59 例患者有骨痛（91%），30 例（46%）有多关节受累。1.0-9.9 岁儿童与青少年（0.7 年[范围：0.2-2.1]）和成人（1.8 年[范围：0.3-3.7，P<0.001]）相比，ALL 与 ON 诊断之间的中位间隔时间明显更短（P<0.001）。女性是青少年患者的危险因素（风险比[HR]为 2.1，95%置信区间[CI]为 1.1-4.2），但不是 1.1-9.9 岁儿童（HR 为 2.4，95%CI 为 0.9-6.2，P=0.08）或 19-45 岁成人（HR 为 1.1，95%CI 为 0.3-4.0）。ALL 诊断时年龄大于 10 岁（比值比[OR]为 3.7，P=0.026）和 ON 诊断时多个关节受累（OR 为 3.4，P=0.027）是发生严重 ON 的危险因素。