Myeloablative Busulfan, Fludarabine and Melphalan Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Childhood Myeloid Malignancy.

[BACKGROUND] Allogeneic hematopoietic stem cell transplant (HSCT) is a proven curative therapy for children with high-risk myeloid malignancies. Disease relapse, transplant-related mortality and graft versus host disease (GvHD) are the main causes of treatment failure and death post-transplant. The optimum pretransplant conditioning regimen is yet to be defined. There is limited data regarding the use of busulfan, fludarabine and melphalan as a myeloablative conditioning regimen in children receiving HSCT for myeloid malignancies.

[AIM] To evaluate the outcome of pharmacokinetic-guided busulfan dosing, in addition to fludarabine and melphalan, as a myeloablative conditioning regimen in children with myeloid malignancies.

[METHODS] We conducted a retrospective, single-center study of all patients <18 years of age who received busulfan, fludarabine, and melphalan conditioning prior to HSCT for myeloid malignancies between January 2013 and June 2023.

[RESULTS] Thirteen children were included in the study. Seven were heavily pretreated with two or more lines of therapy prior to HSCT. All thirteen had neutrophil engraftment and twelve had platelet engraftment. Mucositis was the only significant regimen-related toxicity, which completely resolved with standard management. Acute and chronic GVHD were seen in seven and two patients respectively, with favorable outcomes. One patient was salvaged following cytogenetic relapse, one died following morphological relapse, and one patient succumbed to infection. Eleven patients are currently alive without evidence of leukemia, myelodysplasia, or GvHD.

[CONCLUSION] Busulfan, fludarabine and melphalan conditioning was well tolerated and effective, representing a suitable treatment option for heavily pretreated children with high-risk myeloid malignancies prior to HSCT.