Clinical Impact of Extramedullary Disease on Allogeneic Hematopoietic Cell Transplantation in Pediatric Acute Myeloid Leukemia: A Nationwide Retrospective Study

Introduction Children with acute myeloid leukemia (AML) commonly have extramedullary disease (EMD), which occurs as lesions in the central nervous system (CNS) and as myeloid sarcoma (MS) in the skin, obit, bones, gingivae, and solid organs. Currently, the impact of EMD on outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric AML patients is unclear. Objectives We aimed to determine the impact of EMD on allo-HCT in pediatric AML patients and identify factors influencing the clinical outcome in these patients. Methods Data from 678 children (median age, 7 years; range, 0.3–15 years) who underwent their first allo-HCT for de novo AML between 2006 and 2016 were obtained from the Japanese Data Center for Hematopoietic Cell Transplantation. We then compared outcomes between patients with EMD at diagnosis [EMD group, n = 158; consisting of CNS lesion (n = 47), CNS lesion + MS (n = 9), and MS (n = 102)] and those without EMD (non-EMD group, n = 520). The median follow-up period for survivors was 4.5 years. Results In patients with EMD, lesions occurred in the CNS (n = 56), liver/spleen/lymphoid tissue (n = 35), bone (n = 25), skin (n = 24), orbit (n = 21), oral cavity/paranasal sinus (n = 21), kidney/urinary tract (n = 5), testes (n = 3), and other regions (n = 6), with some overlap. Patients in the EMD group tended to be younger at diagnosis (median age of 2 vs. 7, P P P P  = 0.25 and 0.02), respectively. Leukemia-free survival (LFS) rates at 4 years were 53% in the EMD group and 51% in the non-EMD group ( P  = 0.99). The combination of lesions in the CNS and MS was associated with a poor prognosis ( P  = 0.06). Subgroup analysis by remission status showed similar results, but the presence of bone lesions was associated with poor outcomes after allo-HCT in non-remission AML (LFS rates at 4 years, 0% for patients with bone lesions vs. 27% for patients without, P  = 0.03). Multivariate analysis revealed that EMD did not impact the transplant outcomes and identified that the remission status and PS were independent prognosis factors for LFS after allo-HCT in pediatric AML patients with EMD. Conclusion Our data suggest that the presence of EMD in pediatric AML does not influence transplant outcomes and should thus not be considered a poor prognostic factor. However, bone lesions may be associated with poor prognosis after allo-HCT in non-remission AML. A larger international study is warranted to confirm these findings.