Results
Patient, disease and transplant characteristics:Twenty-three pediatric and young adult patients with myeloid malignancies underwent allo-HCT following BU-FLU-MEL conditioning. The clinical characteristics of the patients are outlined in Table 1 . The median age at transplant was 15.4 years (0.6 to 27.2 years). Seventeen patients were male. Ethnic and/or racial minorities constituted 48% of all patients, the majority of whom (35%) were Hispanic.
Seventeen patients had AML with fourteen being de novo , one evolving from MDS and two were treatment related (t-AML) secondary to osteogenic and Ewings sarcoma therapy. The remaining patients included four patients with MDS, two of which were treatment related secondary to acute lymphoblastic leukemia (ALL) therapy, and two patients had chronic myeloid leukemia (CML). Most AML patients were transplanted in first remission (76%) while five MDS patients (including an MDS patient evolving to AML) did not receive conventional chemotherapy prior to conditioning (Table 1) . Cytogenetics were unfavorable in the majority of AML/MDS patients (Table 1) while the pediatric disease risk index (DRI) was intermediate in 71%, and high or very high in 19%21. Two patients with CML are included in this analysis, with one undergoing allo-HCT following accelerated phase while the other had T315I mutation in the BCR-ABL1 kinase domain.
Seven patients received PBSCT from an HLA-matched sibling. Unrelated donor allo-HCT included two patients who received a MUD PBSC graft, one patient who received a UCB unit and two patients who were infused with double UCB units. Eleven patients underwent T-cell replete haplo-BMT.
Engraftment and chimerism: All patients had trilineage engraftment with complete donor chimerism on their day +28 bone marrows biopsies. One patient who received haplo-BMT experienced secondary graft failure after early CMV reactivation and treatment with ganciclovir. He was salvaged 46 days after the initial transplant using a single day conditioning regimen followed by infusion of unmanipulated G-CSF mobilized PBSC from his original maternal donor and engrafted promptly (day +14)22, 23. All patients when re-assessed by peripheral blood chimerisms on days +100, +180 and +365 remained complete donor chimeras.
Graft-versus-host disease: The cumulative incidence of grades II-IV and III-IV acute GvHD (aGvHD) was 44.8% (Figure 1A) (MSD/MUD-PB 66.7% vs haplo-BMT 19.2%; P=0.039 )(Figure 1B) and 17.8% respectively (MSD/MUD-PB 33.3% vs haplo-BMT 10%; P=0.196 ) (Figure 1B) . The cumulative incidence of chronic GvHD (cGvHD) was 27.3% (Figure 1C)(MSD/MUD-PB 66.7% vs haplo-BMT 0%; P=0.002 ) (Figure 1D) and severe cGvHD was 9.1% respectively (Figure 1C ). Of the six patients with cGVHD (1 mild, 3 moderate, 2 severe) three previously had grade III-IV aGvHD, two had grade II aGvHD and one developed de novo cGvHD seven months after MSD PBSCT while off immunosuppression. Five of six patients required systemic steroid therapy and three were also given ruxolitinib with resolution/improvement of their cGvHD symptoms. Two patients continue on cGvHD therapy.
Survival: Two patients (8.7%) required admission to the intensive care unit (ICU) within their first 100 days post-allo-HCT. One patient developed hyperammonemia due to Ureaplasma parvum with metabolic encephalopathy necessitating intubation and mechanical ventilation24. The other patient was transferred to ICU because of mucositis needing brief intubation for airway support. Only one patient with infant AML who underwent haplo-BMT (paternal donor) in CR1 with 1.8% minimal residual disease (MRD)+ relapsed 13.6 months following transplantation resulting in a cumulative incidence of relapse of 4.5%. This patient received a second haplo-BMT (maternal donor) 16.6 months after the first and remains in remission without GvHD 8.2 months post second haplo-BMT. With a median follow-up of 39.6 months (range 11 to 115 months) the OS is 100% and PFS 95.5% (Figure 1E ). Taking into consideration both relapse and grade III-IV acute or chronic GvHD requiring systemic treatment, the GRFS is 67.8% (Figure 1E ) with haplo-BMT recipients having significantly improved GRFS 83.3% compared to 40% in patients receiving MSD or MUD PBSCT (P=0.025 ) (Figure 1F ).