Busulfan and subsequent malignancy: An evidence-based risk assessment

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Busulfan is an alkylating agent used in conditioning before gene therapy for nonmalignant disorders.
• The incidence of secondary malignancies associated with busulfan is considered low but poorly characterized.
• Precise characterization of busulfan's contribution to secondary malignant risk is warranted.

Purpose of the Study:

• To assess the incidence of secondary malignancies following busulfan exposure.
• To characterize the long-term effects of busulfan, particularly secondary cancers.
• To evaluate busulfan's role in conditioning for gene therapy in nonmalignant conditions.

Main Methods:

• Literature-based assessment of busulfan and late effects, focusing on secondary malignancies.
• PubMed searches were conducted to identify relevant publications.
• Studies with at least 3 years of follow-up were selected for analysis.

Main Results:

• Reviewed 8 pediatric and 13 adult publications involving 570 pediatric and 2076 adult hematopoietic cell transplant (HCT) recipients.
• Secondary malignancies occurred in 0.5% of pediatric HCT recipients (no MDS or AML).
• Fatal secondary malignancies were reported in 0.8% of adult HCT recipients; overall incidence was 4.8% in a subset.
• In gene therapy studies (215 patients), two malignancies were reported in sickle cell disease (SCD) patients, one potentially busulfan-related.

Conclusions:

• The incidence of busulfan-related secondary malignancies is low.
• Risk is likely substantially less than 1% in pediatric transplant recipients.
• Risk is particularly low for pediatric patients receiving busulfan monotherapy for nonmalignant conditions, excluding SCD.