Busulfan and subsequent malignancy: An evidence‐based risk assessment

Background 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 char...

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Published in:	Pediatric blood & cancer Vol. 71; no. 1; pp. e30738 - n/a
Main Authors:	Long‐Boyle, Janel R., Kohn, Donald B., Shah, Ami J., Spencer, Sueli Marques, Sevilla, Julian, Booth, Claire, López Lorenzo, José Luis, Nicoletti, Eileen, Shah, Arpita, Reatz, Meredith, Matos, Joana, Schwartz, Jonathan D.
Format:	Journal Article
Language:	English
Published:	Glenview Wiley Subscription Services, Inc 01-01-2024
Subjects:	Acute myeloid leukemia Busulfan busulfan conditioning Fludarabine Gene therapy Hematology hematopoietic cell transplant Hematopoietic stem cells Malignancy Myelodysplastic syndrome Oncology Pediatrics Risk assessment secondary malignancies Sickle cell disease Stem cell transplantation Treosulfan
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Summary:	Background 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. Procedure 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. Results 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. Conclusion 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1545-5009 1545-5017
DOI:	10.1002/pbc.30738