Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation

Abstract Background Allogeneic hematopoietic cell transplantation (allo‐HCT) remains a curative option for patients with high‐risk myeloid malignancies. Procedure We present our 10‐year experience (October 2012 to October 2021) of consecutive allo‐HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose—busulfan (BU), fludarabine (FLU), and melphalan (MEL). Twenty‐three children, adolescents, and young adult patients (CAYA) (median age 15.4 years) with acute myeloid leukemia (AML, n = 17), myelodysplastic syndrome (MDS, n = 4), or chronic myeloid leukemia (CML, n = 2) underwent allo‐HCT post‐BU‐FLU‐MEL. Four patients had treatment‐related AML/MDS. Donor/stem cell source was matched sibling donor (MSD) PBSC ( n = 7), matched unrelated donor (MUD) PBSC ( n = 2), umbilical cord blood (UCB) ( n = 3), or haploidentical‐BMT ( n = 11). Risk stratification was low ( n = 2), intermediate ( n = 15), high ( n = 3), and very high risk ( n = 1). The two patients with CML had failed tyrosine kinase inhibitor therapies. Results With a median follow‐up of 41.6 months, the relapse rate is only 4.5% with an overall survival (OS) 100%, progression‐free survival (PFS) 95.5%, and graft‐versus‐host‐free‐relapse‐free survival (GRFS) 67.8%. The donor source and the acute graft‐versus‐host disease (GvHD) prophylaxis regimen significantly impacted grade II–IV aGvHD 66.7% versus 19.2% ( p = .039 ) and chronic graft‐versus‐host‐disease (cGvHD) 66.7% versus 0% ( p = .002 ) in the patients receiving MSD or MUD PBSC compared to haplo‐BMT, respectively, resulting in improved GRFS in haplo‐BMT, 83.3% compared to 40% matched donor peripheral blood stem cell transplant (PBSCT) ( p = .025 ). Conclusions Our results demonstrate that BU‐FLU‐MEL is efficacious conditioning for disease control in young patients with myeloid malignancies undergoing MSD or alternative donor allo‐HCT, but in the setting of PBSC grafts with cyclosporine A‐methotrexate (CSA‐MTX) GvHD prophylaxis, it results in an unacceptably high incidence of GvHD.