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.