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成人急性髓系白血病强化治疗后的第二原发性非髓系恶性肿瘤:一项基于丹麦人群的队列研究。

Second primary non-myeloid malignancies following intensive treatment for adult acute myeloid leukaemia: a Danish population-based cohort study.

作者信息

Nielsen Nanna Nørtoft, Jensen Jonas Faartoft, Baech Joachim, Trab Trine, El-Galaly Tarec Christoffer, Schöllkopf Claudia, Ørskov Andreas Due, Ommen Hans Beier, Granfeldt Lene Sofie, Kristensen Daniel Tuyet, Severinsen Marianne Tang

机构信息

Department of Haematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.

Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

Lancet Reg Health Eur. 2024 Dec 30;50:101204. doi: 10.1016/j.lanepe.2024.101204. eCollection 2025 Mar.

Abstract

BACKGROUND

Second primary malignancies (SPMs) are a well-known, long-term complication of antineoplastic treatment. This nationwide cohort study examined the risk of non-myeloid SPMs in survivors of adult acute myeloid leukaemia (AML) treated with intensive chemotherapy and, in some cases, allogeneic stem cell transplantation (alloSCT), compared to a matched general population.

METHODS

Patients with incident AML between 2000 and 2018, alive and aged 18-70 years two years after start of intensive chemotherapy, were included and matched 1:10 to comparators from the general Danish population on sex, age, and the Nordic Multimorbidity Index. Exclusion criteria were non-myeloid SPMs for both AML survivors and comparators.

FINDINGS

A total of 750 AML survivors and 7500 comparators were followed for a median of 10.6 years. The hazard ratio (HR) of non-myeloid SPMs was 1.55 (95% confidence interval [CI] 1.27-1.89) for AML survivors compared to comparators, driven by non-melanoma skin cancer (HR 2.52, 95% CI 1.90-3.35), not of solid cancer (HR 1.14, 95% CI 0.87-1.49). The 10-year cumulative incidences of any non-myeloid SPM were 13.5% (95% CI 10.6-16.5%) in AML survivors and 11.9% (95% CI 11.1-12.8%) in matched comparators. Additionally, AML survivors consolidated with alloSCT had a higher hazard rate of non-myeloid SPMs compared to non-transplanted AML survivors (adjusted HR 1.50, 95% CI 1.00-2.26).

INTERPRETATION

The increased rate of non-myeloid SPMs observed in this population-based cohort study of AML survivors was almost entirely driven by non-melanoma skin cancer and is thus outweighed by the importance of intensive chemotherapy.

FUNDING

Svend Andersen, Heinrich Kopps, and Karen Elise Jensen's Foundation.

摘要

背景

第二原发性恶性肿瘤(SPM)是抗肿瘤治疗一种广为人知的长期并发症。这项全国性队列研究调查了接受强化化疗以及在某些情况下接受异基因干细胞移植(alloSCT)的成年急性髓系白血病(AML)幸存者发生非髓系SPM的风险,并与匹配的普通人群进行比较。

方法

纳入2000年至2018年间确诊的AML患者,在强化化疗开始两年后存活且年龄在18至70岁之间,按照1:10的比例与丹麦普通人群中的对照者进行匹配,匹配因素包括性别、年龄和北欧多病指数。排除标准为AML幸存者和对照者均患有非髓系SPM。

研究结果

共对750名AML幸存者和7500名对照者进行了中位时间为10.6年的随访。与对照者相比,AML幸存者发生非髓系SPM的风险比(HR)为1.55(95%置信区间[CI] 1.27 - 1.89),主要由非黑色素瘤皮肤癌导致(HR 2.52,95% CI 1.90 - 3.35),而非实体癌的风险比为1.14(95% CI 0.87 - 1.49)。AML幸存者中任何非髓系SPM的10年累积发病率为13.5%(95% CI 10.6 - 16.5%),匹配的对照者为11.9%(95% CI 11.1 - 12.8%)。此外,与未接受移植的AML幸存者相比,接受alloSCT巩固治疗的AML幸存者发生非髓系SPM的风险率更高(调整后HR 1.50,95% CI 1.00 - 2.26)。

解读

在这项基于人群的AML幸存者队列研究中观察到的非髓系SPM发生率增加几乎完全由非黑色素瘤皮肤癌导致,因此强化化疗的重要性超过了这一风险。

资助

斯文德·安德森、海因里希·科普斯和卡伦·埃莉斯·詹森基金会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3da1/11750488/b10223436ace/gr1.jpg

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