Transplantation and cellular therapy · 2026
Overcoming Primary Graft Failure in Pediatric Allogeneic HSCT: Insights from Ten Centers of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).
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Daniel Mariona Morell, Romero Melissa Panesso, Carabante Maria Isabel Benítez, Enríquez Sara Vinagre, Forniels Mercedes Plaza, Torija Ivan López, Erburu Andrea Urtasun, Bueno David, Gómez Graciela, Fuentes Carolina, Hurtado Jose Maria Pérez, Amorós Jaime Verdú, Hoyos Santiago Pérez, Oficialdegui M Luz Uría, García Laura Alonso, Diaz-de-Heredia Cristina
Аннотация
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for malignant and non-malignant diseases; however, primary graft failure (GF) is a life-threatening complication, particularly with the increasing use of alternative donors and reduced-intensity conditioning (RIC) strategies. Data on outcomes and optimal management-especially in the pediatric population-remain limited and heterogeneous.
OBJECTIVES: The primary endpoint was overall survival (OS) in patients with primary GF. Secondary endpoints included OS in patients with primary GF after salvage HSCT and the evaluation of risk factors associated with engraftment and survival.
METHODS: We conducted a multicenter, retrospective, observational study including pediatric patients (<18 years) diagnosed with primary GF after a first allogeneic HSCT between January 2011 and July 2022 across 10 Spanish pediatric transplant centers.
RESULTS: A total of 1561 allogeneic HSCTs were performed. Fifty-seven patients developed primary GF, yielding an overall incidence of 3.65%, which was higher among transplants with donors with HLA disparities. One-year OS for patients with primary GF was 73%. Over 90% of patients underwent salvage HSCT, with 74% achieving engraftment. No risk factors for engraftment were identified. One-year OS after the second HSCT was 71%. Achieving engraftment after the second transplant was the only factor significantly associated with survival (1-year OS, 81% [95% CI, 65-90] vs. 43% [95% CI, 17-66]; p < 0.001). No other clinical or transplant-related variables showed significant associations with survival.
CONCLUSIONS: GF remains a major challenge and continues to limit the overall success of HSCT. The majority of patients underwent a second transplant, with engraftment achieved in 74% of patients. Overall survival was 68% at 2 years after the first transplant. The frequent use of RIC regimens including fludarabine and serotherapy in patients undergoing retransplantation reflects a commonly adopted clinical practice, although no specific conditioning regimen was significantly associated with engraftment or survival.
OBJECTIVES: The primary endpoint was overall survival (OS) in patients with primary GF. Secondary endpoints included OS in patients with primary GF after salvage HSCT and the evaluation of risk factors associated with engraftment and survival.
METHODS: We conducted a multicenter, retrospective, observational study including pediatric patients (<18 years) diagnosed with primary GF after a first allogeneic HSCT between January 2011 and July 2022 across 10 Spanish pediatric transplant centers.
RESULTS: A total of 1561 allogeneic HSCTs were performed. Fifty-seven patients developed primary GF, yielding an overall incidence of 3.65%, which was higher among transplants with donors with HLA disparities. One-year OS for patients with primary GF was 73%. Over 90% of patients underwent salvage HSCT, with 74% achieving engraftment. No risk factors for engraftment were identified. One-year OS after the second HSCT was 71%. Achieving engraftment after the second transplant was the only factor significantly associated with survival (1-year OS, 81% [95% CI, 65-90] vs. 43% [95% CI, 17-66]; p < 0.001). No other clinical or transplant-related variables showed significant associations with survival.
CONCLUSIONS: GF remains a major challenge and continues to limit the overall success of HSCT. The majority of patients underwent a second transplant, with engraftment achieved in 74% of patients. Overall survival was 68% at 2 years after the first transplant. The frequent use of RIC regimens including fludarabine and serotherapy in patients undergoing retransplantation reflects a commonly adopted clinical practice, although no specific conditioning regimen was significantly associated with engraftment or survival.