Blood Res 2018; 53(1):
Published online March 31, 2018
https://doi.org/10.5045/br.2018.53.1.1
© The Korean Society of Hematology
Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pediatric acute myeloid leukemias (AMLs) are a heterogeneous group of diseases that can be classified based on morphology, lineage, and genetics. Recent improvements in the outcomes of pediatric AML reflect the use of intensive chemotherapy and post-remission treatment with additional anthracyclines and high-dose cytarabine or hematopoietic stem cell transplantation (HSCT). Advances in supportive care allowing for the administration of optimally intensive therapy with low morbidity and mortality rates have also contributed to improving the survival rates of patients with pediatric AML. As a result, several groups now achieve complete remission (CR) rates of 80–90%, relapse rates of 30–40%, event-free survival (EFS) rates of 50%, and overall survival (OS) rates of nearly 70% [1]. Along with the improvement of therapeutic strategies, progress in genomic research has revealed numerous somatic, karyotypic, and molecular alterations in pediatric AML. State-of-the-art sequencing technology has identified clinically significant genetic abnormalities that have been since incorporated in clinical practice for risk stratification of adult
In this issue of
Risk stratification based on genetic abnormalities is a critical determinant for predicting outcomes of pediatric AML. In the study by Song et al., patients with adverse cytogenetics showed significantly poorer outcomes than those with favorable cytogenetics, including t(8;21) or inv(16). With the progress in sequencing technologies, many genetic abnormalities of prognostic significance have been identified. Mutations of the nucleophosmin 1 gene or biallelic mutations of the CCAAT/enhancer-binding protein-alpha gene are now accepted generally as mutations conferring favorable prognosis in children [5,6]. Besides risk stratification at diagnosis, the measurement of minimal residual disease to evaluate the response to therapy is perhaps the best predictor of relapse. Assessments of genetic features at diagnosis and response to therapy have become routine for risk stratification in most current clinical trials.
HSCT is another important treatment modality that has improved the outcomes of AML in children. In the study by Song et al. ≥60% of patients received HSCT, which demonstrated the survival benefit of HSCT over chemotherapy alone. Moreover, they also reported that patients who received autologous HSCT showed worse survival than those who received allogeneic HSCT. Therefore, autologous HSCT was abandoned in their recent cohort. Although autologous HSCT has no advantages over chemotherapy, allogeneic HSCT remains a viable option for a significant proportion of patients with pediatric AML. Additionally, while the survival of patients with pediatric AML with favorable risk features is excellent with chemotherapy alone, HSCT continues to be a critical component of treatment for selected patients, particularly those with high-risk or advanced AML. Remarkable improvements have been made in the field of HSCT in children and adolescents over the last decade because of the development of optimal conditioning regimens, more effective graft-versus-host disease (GVHD) prophylaxis, and advancements in post-transplant care. In an experienced transplant center, patients who received HSCT from a matched unrelated donor (URD) showed similar outcomes to those who received HSCT from a human leukocyte antigen (HLA)-matched sibling donor (MSD) [7,8]. Furthermore, the outcomes of HSCT even with an alternative donor, including transplants using umbilical cord blood or a haploidentical family donor, significantly improved [9,10]. In Song et al.'s study HSCT from MSD showed a favorable outcome of 80%, while that from URD showed a comparable outcome. Although there is no consensus regarding the indication for HSCT upon achieving the first CR, most investigators recommend allogeneic HSCT to patients with high-risk features or a poor response to therapy. Recent advances in HSCT with low transplant-related mortality due to better supportive care, adequate management of infections, effective GVHD prophylaxis, and optimal conditioning, along with an expanded donor pool, justify the application of allogeneic HSCT based on a refined risk group stratification to maximize the outcomes of pediatric AML.
Although the survival in pediatric AML has improved over the last decades, several unresolved issues, including the optimal intensity and combination of chemotherapy, benefits of allogeneic HSCT upon achieving the first CR, and use of risk-directed and response-based therapy, remain. Nationwide collaboration is essential to establish the most effective therapy with the lowest toxicity for pediatric AML. Furthermore, sustained progress in understanding the biology of AML and the concomitant development of new targeted agents for use in combination with conventional chemotherapeutic drugs will further improve the outcomes of pediatric AML.
Blood Res 2018; 53(1): 1-2
Published online March 31, 2018 https://doi.org/10.5045/br.2018.53.1.1
Copyright © The Korean Society of Hematology.
Ho Joon Im, M.D. Ph.D.*
Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pediatric acute myeloid leukemias (AMLs) are a heterogeneous group of diseases that can be classified based on morphology, lineage, and genetics. Recent improvements in the outcomes of pediatric AML reflect the use of intensive chemotherapy and post-remission treatment with additional anthracyclines and high-dose cytarabine or hematopoietic stem cell transplantation (HSCT). Advances in supportive care allowing for the administration of optimally intensive therapy with low morbidity and mortality rates have also contributed to improving the survival rates of patients with pediatric AML. As a result, several groups now achieve complete remission (CR) rates of 80–90%, relapse rates of 30–40%, event-free survival (EFS) rates of 50%, and overall survival (OS) rates of nearly 70% [1]. Along with the improvement of therapeutic strategies, progress in genomic research has revealed numerous somatic, karyotypic, and molecular alterations in pediatric AML. State-of-the-art sequencing technology has identified clinically significant genetic abnormalities that have been since incorporated in clinical practice for risk stratification of adult
In this issue of
Risk stratification based on genetic abnormalities is a critical determinant for predicting outcomes of pediatric AML. In the study by Song et al., patients with adverse cytogenetics showed significantly poorer outcomes than those with favorable cytogenetics, including t(8;21) or inv(16). With the progress in sequencing technologies, many genetic abnormalities of prognostic significance have been identified. Mutations of the nucleophosmin 1 gene or biallelic mutations of the CCAAT/enhancer-binding protein-alpha gene are now accepted generally as mutations conferring favorable prognosis in children [5,6]. Besides risk stratification at diagnosis, the measurement of minimal residual disease to evaluate the response to therapy is perhaps the best predictor of relapse. Assessments of genetic features at diagnosis and response to therapy have become routine for risk stratification in most current clinical trials.
HSCT is another important treatment modality that has improved the outcomes of AML in children. In the study by Song et al. ≥60% of patients received HSCT, which demonstrated the survival benefit of HSCT over chemotherapy alone. Moreover, they also reported that patients who received autologous HSCT showed worse survival than those who received allogeneic HSCT. Therefore, autologous HSCT was abandoned in their recent cohort. Although autologous HSCT has no advantages over chemotherapy, allogeneic HSCT remains a viable option for a significant proportion of patients with pediatric AML. Additionally, while the survival of patients with pediatric AML with favorable risk features is excellent with chemotherapy alone, HSCT continues to be a critical component of treatment for selected patients, particularly those with high-risk or advanced AML. Remarkable improvements have been made in the field of HSCT in children and adolescents over the last decade because of the development of optimal conditioning regimens, more effective graft-versus-host disease (GVHD) prophylaxis, and advancements in post-transplant care. In an experienced transplant center, patients who received HSCT from a matched unrelated donor (URD) showed similar outcomes to those who received HSCT from a human leukocyte antigen (HLA)-matched sibling donor (MSD) [7,8]. Furthermore, the outcomes of HSCT even with an alternative donor, including transplants using umbilical cord blood or a haploidentical family donor, significantly improved [9,10]. In Song et al.'s study HSCT from MSD showed a favorable outcome of 80%, while that from URD showed a comparable outcome. Although there is no consensus regarding the indication for HSCT upon achieving the first CR, most investigators recommend allogeneic HSCT to patients with high-risk features or a poor response to therapy. Recent advances in HSCT with low transplant-related mortality due to better supportive care, adequate management of infections, effective GVHD prophylaxis, and optimal conditioning, along with an expanded donor pool, justify the application of allogeneic HSCT based on a refined risk group stratification to maximize the outcomes of pediatric AML.
Although the survival in pediatric AML has improved over the last decades, several unresolved issues, including the optimal intensity and combination of chemotherapy, benefits of allogeneic HSCT upon achieving the first CR, and use of risk-directed and response-based therapy, remain. Nationwide collaboration is essential to establish the most effective therapy with the lowest toxicity for pediatric AML. Furthermore, sustained progress in understanding the biology of AML and the concomitant development of new targeted agents for use in combination with conventional chemotherapeutic drugs will further improve the outcomes of pediatric AML.