Haploidentical hematopoietic stem cell transplantation in pediatric and adolescent patients: A study of the Spanish hematopoietic stem cell transplantation group (GETH)

Introduction: The main advantages of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are the immediate availability of donors, the possibility of developing cell therapy approaches with different novel transplant platforms, and the procedure's cost savings.MethodologyWe retrospectively analyzed the pediatric haplo-HSCT activity of the Spanish hematopoietic stem-cell transplantation group (GETH) between 1999 and 2016, aiming to study clinical characteristics and outcomes by describing patient groups with non-malignant disease (NMD) or malignant disease (MD) and the impact of 2 different periods (1999–2009 and 2010–2016) on long-term outcomes.ResultsTwelve centers performed 232 haplo-HSCTs in 227 children, representing 10% of all pediatric allogeneic HSCT activity in Spain from 1999 to 2016, with a notable increase since 2013. Most haplo-HSCTs (86.7%) were performed in patients with MD; 95% received peripheral blood stem cells from donors, and 78.9% received ex vivo T-cell depleted grafts. Non-manipulated grafts using post-transplantation cyclophosphamide have been incorporated since 2012. We observed a higher percentage of graft failure in NMD versus MD (32% vs. 15.6%; p=0.029). Relapse and transplant-related mortality were the procedure's main limitations in MD and NMD, respectively. Five-year overall survival was 48.5% (SE 3.9), with no statistically significant difference when comparing the MD and NMD cohorts. Patients who received previously a HSCT the overall survival was significantly decreased. We observed no survival improvement over time.ConclusionsAlthough haplo-HSCT is an increasingly employed treatment option, our patients’ results need improvement. We need to develop reference centers, especially for NMD whose rarity makes it difficult to gain experience. (AU)

Introducción: Las principales ventajas del trasplante de progenitores hematopoyéticos de donante haploidéntico (haplo-TPH) son la disponibilidad inmediata de donantes, la posibilidad de desarrollar terapia celular postrasplante y el ahorro de costes al obviar el proceso de búsqueda de donante.MetodologíaAnalizamos retrospectivamente la actividad haplo-TPH en población pediátrica del grupo español de trasplante hematopoyético (GETH) entre 1999 y 2016, con el objetivo de estudiar las características clínicas y los resultados mediante la descripción de grupos de pacientes con enfermedad no malignas (ENM) o enfermedad maligna (EM) y el impacto de dos períodos diferentes (1999-2009 y 2010-2016) en los resultados a largo plazo.ResultadosDoce centros realizaron 232 haplo-TPH en 227 niños, lo que representa el 10% de toda la actividad de TPH alogénicos pediátricos en España entre 1999-2016, con un aumento notable desde 2013. La mayoría de los haplo-TPH (86,7%) se realizaron en pacientes con EM; el 95% recibió progenitores hematopoyéticos de sangre periférica y el 78,9% recibió injertos con purgado de células T ex vivo. Los injertos no manipulados con ciclofosfamida postrasplante se realizaron a partir de 2012. Observamos un mayor porcentaje de fallos del injerto en la ENM que en la EM (32% frente a 15,6%; p=0,029). La recaída y la mortalidad relacionada con el trasplante fueron las principales limitaciones del procedimiento en la EM y la ENM, respectivamente. La supervivencia global a cinco años fue del 48,5% (EE 3,9), sin diferencias estadísticamente significativas al comparar las cohortes con EM y ENM. En los pacientes que recibieron previamente un TPH, la supervivencia global se redujo significativamente. No observamos mejoría en la supervivencia a lo largo del tiempo. (AU)

Haploidentical hematopoietic stem cell transplantation in pediatric and adolescent patients: A study of the Spanish hematopoietic stem cell transplantation group (GETH).

INTRODUCTION: The main advantages of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are the immediate availability of donors, the possibility of developing cell therapy approaches with different novel transplant platforms, and the procedure's cost savings. METHODOLOGY: We retrospectively analyzed the pediatric haplo-HSCT activity of the Spanish hematopoietic stem-cell transplantation group (GETH) between 1999 and 2016, aiming to study clinical characteristics and outcomes by describing patient groups with non-malignant disease (NMD) or malignant disease (MD) and the impact of 2 different periods (1999-2009 and 2010-2016) on long-term outcomes. RESULTS: Twelve centers performed 232 haplo-HSCTs in 227 children, representing 10% of all pediatric allogeneic HSCT activity in Spain from 1999 to 2016, with a notable increase since 2013. Most haplo-HSCTs (86.7%) were performed in patients with MD; 95% received peripheral blood stem cells from donors, and 78.9% received ex vivo T-cell depleted grafts. Non-manipulated grafts using post-transplantation cyclophosphamide have been incorporated since 2012. We observed a higher percentage of graft failure in NMD versus MD (32% vs. 15.6%; p=0.029). Relapse and transplant-related mortality were the procedure's main limitations in MD and NMD, respectively. Five-year overall survival was 48.5% (SE 3.9), with no statistically significant difference when comparing the MD and NMD cohorts. Patients who received previously a HSCT the overall survival was significantly decreased. We observed no survival improvement over time. CONCLUSIONS: Although haplo-HSCT is an increasingly employed treatment option, our patients' results need improvement. We need to develop reference centers, especially for NMD whose rarity makes it difficult to gain experience.