Original Article

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Blood Res 2018; 53(1):

Published online March 31, 2018

https://doi.org/10.5045/br.2018.53.1.25

© The Korean Society of Hematology

Improvement of treatment outcome over 2 decades in children with acute myeloid leukemia

Tae Yang Song1, Sang Hoon Lee1, Gun Kim1, Hee Jo Baek1,2, Tai Ju Hwang1, and Hoon Kook1,2*

1Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

2Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Correspondence to : Hoon Kook, M.D., Ph.D. Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun 58128, Korea. hoonkook@chonnam.ac.kr

Received: July 17, 2017; Revised: August 30, 2017; Accepted: September 21, 2017

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.

Abstract

Background

The prognosis of pediatric acute myeloid leukemia (AML) has recently improved. This study aimed to describe the epidemiology, changes in treatment strategies, and improvement of outcomes in Gwangju-Chonnam children with AML over 2 decades.

Methods

Medical records of 116 children with newly diagnosed AML were retrospectively reviewed for demographic characteristics, prognostic groups including cytogenetic risks, treatment protocols, and survival rates over the periods between 1996 and 2005 (Period I, N=53), and 2006 and 2015 (Period II, N=38).

Results

The annual incidence of AML has decreased with reduced pediatric population. The 5-year Kaplan-Meier (K-M) estimated overall survival (OS) and event-free survival (EFS) rates in 110 AML patients were 53.2±5.1% and 43.8±5.1%, respectively. The 5-year OS rate significantly improved during period II (70.3±7.0%) as compared to that during period I (40.0±6.8%) (P =0.001). The 5-year OS was not significantly different among cytogenetic risk groups (P =0.11). Fifty-eight patients underwent hematopoietic stem cell transplantation (HSCT). The K-M 5-year estimated survival for transplanted patients was 53.7±7.0%, while that for chemotherapy-only patients was 30.1±9.1% (P =0.014). Among the prognostic factors, treatment modality was the only independent factor. The chemotherapy-only group had a relative risk of 2.06 for death compared with the transplantation group (P=0.015).

Conclusion

The survival of Korean children with AML has improved to a level comparable with that of developed countries over 2 decades, owing to a change in induction strategy, better supportive care with economic growth, refinement of HSCT techniques including a better selection of patients based on prognostic groups, and stem cell donor selection.

Keywords Acute myeloid leukemia, Cytogenetics, Child, Hematopoietic stem cell transplantation, Survival rate

Article

Original Article

Blood Res 2018; 53(1): 25-34

Published online March 31, 2018 https://doi.org/10.5045/br.2018.53.1.25

Copyright © The Korean Society of Hematology.

Improvement of treatment outcome over 2 decades in children with acute myeloid leukemia

Tae Yang Song1, Sang Hoon Lee1, Gun Kim1, Hee Jo Baek1,2, Tai Ju Hwang1, and Hoon Kook1,2*

1Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

2Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Correspondence to:Hoon Kook, M.D., Ph.D. Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun 58128, Korea. hoonkook@chonnam.ac.kr

Received: July 17, 2017; Revised: August 30, 2017; Accepted: September 21, 2017

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.

Abstract

Background

The prognosis of pediatric acute myeloid leukemia (AML) has recently improved. This study aimed to describe the epidemiology, changes in treatment strategies, and improvement of outcomes in Gwangju-Chonnam children with AML over 2 decades.

Methods

Medical records of 116 children with newly diagnosed AML were retrospectively reviewed for demographic characteristics, prognostic groups including cytogenetic risks, treatment protocols, and survival rates over the periods between 1996 and 2005 (Period I, N=53), and 2006 and 2015 (Period II, N=38).

Results

The annual incidence of AML has decreased with reduced pediatric population. The 5-year Kaplan-Meier (K-M) estimated overall survival (OS) and event-free survival (EFS) rates in 110 AML patients were 53.2±5.1% and 43.8±5.1%, respectively. The 5-year OS rate significantly improved during period II (70.3±7.0%) as compared to that during period I (40.0±6.8%) (P =0.001). The 5-year OS was not significantly different among cytogenetic risk groups (P =0.11). Fifty-eight patients underwent hematopoietic stem cell transplantation (HSCT). The K-M 5-year estimated survival for transplanted patients was 53.7±7.0%, while that for chemotherapy-only patients was 30.1±9.1% (P =0.014). Among the prognostic factors, treatment modality was the only independent factor. The chemotherapy-only group had a relative risk of 2.06 for death compared with the transplantation group (P=0.015).

Conclusion

The survival of Korean children with AML has improved to a level comparable with that of developed countries over 2 decades, owing to a change in induction strategy, better supportive care with economic growth, refinement of HSCT techniques including a better selection of patients based on prognostic groups, and stem cell donor selection.

Keywords: Acute myeloid leukemia, Cytogenetics, Child, Hematopoietic stem cell transplantation, Survival rate

Fig 1.

Figure 1.

Flow diagram of patients.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 2.

Figure 2.

Annual incidence of newly diagnosed pediatric acute myeloid leukemia.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 3.

Figure 3.

The 5-year Kaplan-Meier estimated (K-M) overall survival (OS) (A) and event-free survival (EFS) (B) for 110 childhood acute myeloid leukemia cases acute promyelocytic leukemia. The OS (C) and EFS (D) were compared according to study period.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 4.

Figure 4.

The 5-year Kaplan-Meier overall survival (K-M OS) (A) and event-free survival (EFS) (B) for 91 childhood acute myeloid leukemia cases, excluding acute promyelocytic leukemia. The OS (C) and EFS (D) were compared according to study period.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 5.

Figure 5.

The 2-year Kaplan-Meier overall survival (K-M OS) (A) and event-free survival (EFS) (B) for 91 childhood acute myeloid leukemia cases by induction regimen.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 6.

Figure 6.

The 5-year Kaplan-Meier overall survival (K-M OS) (A) and event-free survival (EFS) (B) for 91 childhood acute myeloid leukemia cases by cytogenetic prognostic group.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 7.

Figure 7.

The 5-year Kaplan-Meier overall survival (K-M OS) for 91 childhood acute myeloid leukemia cases by treatment modality.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Fig 8.

Figure 8.

The 5-year Kaplan-Meier overall survival (K-M OS) by stem cell sources.

Blood Research 2018; 53: 25-34https://doi.org/10.5045/br.2018.53.1.25

Table 1 . Demographic characteristics of childhood acute myeloid leukemia by study period..

a)Comparison between period I (1996–2005) and period II (2006–2015)..

Abbreviations: WBC, white blood cell count; FAB, French-American-British..


Table 2 . Trend of treatment policy for childhood acute myeloid leukemia by study period..

Abbreviations: AML 2012, double induction regimen consisting of idarubicin (IDA) or mitoxantrone plus cytarabine based chemotherapy; BM, bone marrow; KSBRM, idarubicin plus N4-behenoyl-1-β-D-arabinofuranosyl cytosine (BHAC) based chemotherapy; PB, peripheral blood; UCB, umbilical cord blood..


Table 3 . Outcome following induction therapy in pediatric acute myeloid leukemia cases..

Abbreviations: AML 2012, double induction regimen consisting of idarubicin (IDA) or mitoxantrone plus cytarabine based chemotherapy; KSBRM, idarubicin plus N4-behenoyl-1-β-D-arabinofuranosyl cytosine (BHAC) based chemotherapy; Responder, complete remission plus partial remission..


Table 4 . The 5-year Kaplan-Meier overall survival (K-M OS) and event-free survival (EFS) by prognosis factors..

Abbreviations: BM, bone marrow; EFS, event-free survival; K-M, Kaplan-Meier; OS, overall survival; PB, peripheral blood; UCB, umbilical cord blood; WBC, white blood cell count..


Table 5 . Cox proportional hazards model to predict the prognosis of children with acute myeloid leukemia (AML)..

a)Relative risk (95% confidence interval)..

Abbreviation: CI, Confidence interval..


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