Multiple Hematopoietic Stem Cell Transplantations in Pediatric Acute Myeloid Leukemia: Prognostic Significance of Remission and Severe Sinusoidal Obstruction Syndrome.

Background: Relapsed or refractory cases of pediatric acute myeloid leukemia (AML) have poor outcomes despite advancements in chemotherapy and hematopoietic stem cell transplantation (HSCT). While a second HSCT is often a salvage option, its outcomes vary widely, and prognostic factors remain unclear.

Objectives: This study aimed to evaluate outcomes and identify prognostic factors in pediatric patients with AML who underwent multiple HSCTs.

Methods: We conducted a retrospective, multicenter study of 49 pediatric patients with AML who underwent two or more HSCTs at 18 Japan Association of Childhood Leukemia Study institutions during 2000-2019. Clinical data on patient demographics, disease status, transplant characteristics, and complications were collected. The primary endpoint was 5-year overall survival (OS) after the second HSCT. Kaplan-Meier and multivariate Cox regression analyses were performed.

Results: Of the 49 patients, three and 46 underwent three and two HSCTs, respectively. Among these 46 patients, 5-year OS after the second HSCT was 28.3%. Achieving hematological complete remission (CR) before the second HSCT was associated with significantly better outcomes (5-year OS: 45.0% vs. 0%, p < 0.01). Severe sinusoidal obstruction syndrome (SOS) after the second HSCT was a strong predictor of transplant-related mortality (5-year OS: 0% in severe SOS cases, p < 0.01). Patient age, donor type, conditioning regimen, and acute/chronic graft-versus-host disease were not significantly associated with survival in multivariate analysis.

Conclusions: Achieving CR before the second HSCT is critical for long-term survival, while severe SOS significantly worsens prognosis. Optimized pre-transplant strategies to reduce SOS risk are essential to improve outcomes of pediatric patients with AML who undergo multiple HSCTs.