University of California, San Francisco, California, USA.
University of California, Los Angeles, California, USA.
Pediatr Blood Cancer. 2024 Jan;71(1):e30738. doi: 10.1002/pbc.30738. Epub 2023 Oct 19.
The incidence of secondary malignancies associated with busulfan exposure is considered low, but has been poorly characterized. Because this alkylating agent is increasingly utilized as conditioning prior to gene therapy in nonmalignant hematologic and related disorders, more precise characterization of busulfan's potential contribution to subsequent malignant risk is warranted.
We conducted a literature-based assessment of busulfan and subsequent late effects, with emphasis on secondary malignancies, identifying publications via PubMed searches, and selecting those reporting at least 3 years of follow-up.
We identified eight pediatric and 13 adult publications describing long-term follow-up in 570 pediatric and 2076 adult hematopoietic cell transplant (HCT) recipients. Secondary malignancies were reported in 0.5% of pediatric HCT recipients, with no cases of myelodysplastic syndrome (MDS) or acute myelocytic leukemia (AML). Fatal secondary malignancies were reported in 0.8% of 1887 evaluable adult HCT recipients, and an overall incidence of secondary malignancies of 4.8% was reported in a subset of 389 evaluable adult patients. We also reviewed long-term results from eight publications evaluating lentiviral- and human promotor-based HSC-targeted gene therapy in 215 patients with nonmalignant conditions, in which busulfan/treosulfan monotherapy or busulfan/fludarabine was the only conditioning. Two malignancies were reported in patients with sickle cell disease (SCD), one of which was potentially busulfan-related. No additional malignancies were reported in 173 patients with follow-up of 5-12 years.
The incidence of busulfan-related secondary malignancies is low, and likely to be substantially less than 1% in pediatric transplant recipients, especially those receiving busulfan monotherapy for nonmalignant conditions other than SCD.
与白消安暴露相关的继发性恶性肿瘤的发病率较低，但特征描述较差。由于这种烷化剂在非恶性血液病和相关疾病的基因治疗前越来越多地被用作预处理，因此更准确地描述白消安对随后恶性风险的潜在贡献是必要的。
我们通过 PubMed 搜索进行了基于文献的白消安和随后的晚期效应评估，重点是继发性恶性肿瘤，确定出版物，并选择至少随访 3 年的报告。
我们确定了 8 项儿科和 13 项成人文献，描述了 570 例儿科和 2076 例成人造血细胞移植（HCT）受者的长期随访。儿科 HCT 受者中有 0.5%报告了继发性恶性肿瘤，无骨髓增生异常综合征（MDS）或急性髓细胞性白血病（AML）病例。1887 例可评估的成年 HCT 受者中有 0.8%报告了致命性继发性恶性肿瘤，在 389 例可评估的成年患者亚组中报告了 4.8%的继发性恶性肿瘤总发生率。我们还审查了 8 项文献的长期结果，这些文献评估了非恶性疾病中基于慢病毒和人启动子的 HSC 靶向基因治疗，在 215 例患者中，白消安/硫代硫酸钠单药或白消安/氟达拉滨是唯一的预处理。在镰状细胞病（SCD）患者中报告了 2 例恶性肿瘤，其中 1 例可能与白消安有关。在 173 例随访 5-12 年的患者中未报告其他恶性肿瘤。
白消安相关继发性恶性肿瘤的发病率较低，在儿科移植受者中，尤其是在接受白消安单药治疗非 SCD 以外的非恶性疾病的患者中，发病率很可能远低于 1%。
