Treatment outcome and prognostic factors in relapsed pediatric acute myeloid leukemia

Jung Hwan Lee; Hee Young Ju; Ju Kyung Hyun; So Jin Kim; Hee Won Cho; Jae Kyung Lee; Ji Won Lee; Ki Woong Sung; Keon Hee Yoo

doi:10.5045/br.2023.2023152

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Original Article

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Blood Res 2023; 58(4):

Published online December 31, 2023

https://doi.org/10.5045/br.2023.2023152

Treatment outcome and prognostic factors in relapsed pediatric acute myeloid leukemia

Jung Hwan Lee¹, Hee Young Ju¹, Ju Kyung Hyun¹, So Jin Kim¹, Hee Won Cho¹, Jae Kyung Lee¹, Ji Won Lee¹, Ki Woong Sung¹, Keon Hee Yoo^1,2,3

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¹Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, ²Department of Health Science and Technology, SAIHST, Sungkyunkwan University School of Medicine, ³Cell & Gene Therapy Institute, Samsung Medical Center, Seoul, Korea

Correspondence to : Keon Hee Yoo, M.D., Ph.D.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
E-mail: hema2170@skku.edu

Received: August 9, 2023; Revised: October 23, 2023; Accepted: October 26, 2023

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

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Abstract
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Background
Despite improved outcomes for pediatric patients with acute myeloid leukemia (AML), the prognosis for relapse remains poor. This study aimed to examine the clinical factors associated with prognosis in relapsed pediatric AML.
Methods
We conducted a chart review of pediatric patients with AML who experienced their first relapse and received treatment at our institution between 2008 and 2019. Risk stratification at diagnosis was performed according to the definition suggested by the ongoing AML 2012 study in Korea, and the clinical factors associated with prognosis were analyzed.
Results
A total of 27 pediatric patients with relapsed AML were identified. The 5-year overall survival (OS) and event-free survival (EFS) rates were 32.9% and 32.9%, respectively. A duration ≥12 months from diagnosis to relapse had a favorable impact on survival outcomes (5-yr OS, 64.0% vs. 15.7%; P=0.007). Patients who achieved complete remission (CR) after 1 course of chemotherapy following relapse (N=15) had a 5-year OS rate of 59.3%, while none of the other patients survived (P＜0.0001). Additionally, the 5-year OS differed significantly based on the risk group at initial diagnosis (62.3% [favorable and intermediate prognosis groups, N=11] vs. 13.3% [poor prognosis group, N=15]; P=0.014).
Conclusion
Patients with a longer duration of CR before relapse, who achieved CR following 1 course of reinduction chemotherapy, and were in the favorable or intermediate prognosis group at diagnosis demonstrated better outcomes. These findings emphasize the importance of tailoring treatment strategies based on the expected prognosis at relapse in pediatric patients with AML.

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Keywords: Acute myeloid leukemia, Pediatric, Relapse, Prognosis

Article

Original Article

Blood Res 2023; 58(4): 181-186

Published online December 31, 2023 https://doi.org/10.5045/br.2023.2023152

Treatment outcome and prognostic factors in relapsed pediatric acute myeloid leukemia

Jung Hwan Lee¹, Hee Young Ju¹, Ju Kyung Hyun¹, So Jin Kim¹, Hee Won Cho¹, Jae Kyung Lee¹, Ji Won Lee¹, Ki Woong Sung¹, Keon Hee Yoo^1,2,3

Correspondence to:Keon Hee Yoo, M.D., Ph.D.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
E-mail: hema2170@skku.edu

Received: August 9, 2023; Revised: October 23, 2023; Accepted: October 26, 2023

Abstract

Keywords: Acute myeloid leukemia, Pediatric, Relapse, Prognosis

Abstract

Fig 1.

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Figure 1.Determination of prognosis groups in AML 2012 trial. Both risk features and treatment response were taken into account in determining the prognostic group.
Abbreviations: AMKL, acute megakaryocytic leukemia; CBF, core-binding factor; CR, complete remission; NR, no response; PR, partial response.

Blood Research 2023; 58: 181-186https://doi.org/10.5045/br.2023.2023152

Fig 2.

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Figure 2.Overall survival (OS) and event-free survival (EFS) rates. OS and EFS of all patients with first relapse of pediatric AML (A). Comparisons of OS rates between the early vs. late relapsers (B), those who achieved CR after 1 course of reinduction chemotherapy vs. others (C), and those in the favorable or intermediate prognosis groups (FG+IG) vs. poor prognosis group (PG) (D).

Blood Research 2023; 58: 181-186https://doi.org/10.5045/br.2023.2023152

Table 1 . Patient characteristics..

	N (%)/median (range)
Sex
Male	15 (55.6)
Female	12 (44.4)
Initial WBC count, median (/μL)	20,400 (1,650–265,800)
Age at relapse, median (yr)	6.0 (1.0–18.0)
Interval from diagnosis to first relapse (mo)	7 (2–33)
Remission after 1 course of reinduction
Yes	15 (53.6)
No	12 (46.4)
Prognosis group at initial diagnosis
Favorable	4 (14.8)
Intermediate	7 (25.9)
Poor	15 (55.6)
Not available	1 (3.7)
Relapsed site
BM only	21 (77.8)
EM only	5 (18.5)
BM+EM	1 (3.7)
Molecular abnormality
FTL3-ITD	4 (14.8)
c-KIT in CBF AML	1 (3.7)
CEBPA	2 (7.4)
Others	20 (74.1)

Abbreviations: BM, bone marrow; CBF, core-binding factor; EM, extramedullary..

Table 2 . Univariate analysis of prognostic factors..

	N	5-yr OS (%)	P	5-yr EFS (%)	P	Hazard ratio (95% CI)
Sex
Male	15	38.9	0.745	33.3	0.810	1.175 (0.445–3.052)
Female	12	27.8	0.745	27.3	0.810	1.175 (0.445–3.052)
Initial WBC count (/μL)
<20,000	13	34.6	0.989	33.3	0.951	1.007 (0.378–2.683)
>20,000	13	30.8	0.989	27.7	0.951	1.007 (0.378–2.683)
Age at relapse (yr)
0–10	16	35.0	0.782	30.0	0.908	1.144 (0.430–3.046)
>10	11	34.1	0.782	30.0	0.908	1.144 (0.430–3.046)
Interval from diagnosis to first relapse (mo)
≥12	10	64.0	0.007	60.0	0.008	4.636 (1.792–12.000)
<12	17	15.7	0.007	12.5	0.008	4.636 (1.792–12.000)
Remission after 1 course of reinduction
Yes	15	59.3	<0.0001	59.3	<0.0001	7.206 (2.403–21.610)
No	12	0.0	<0.0001	0.0	<0.0001	7.206 (2.403–21.610)
Prognostic group
FG+IG	11	62.3	0.014	60.0	0.002	3.640 (1.360–9.743)
PG	15	13.3	0.014	10.0	0.002	3.640 (1.360–9.743)
Relapsed site
BM only	21	33.3	0.258	33.0	0.676
EM only	5	40.0		40.0
BM+EM	1	0.0		0.0
Molecular abnormality
FTL3-ITD	4	0.0	0.019	0.0	0.109
c-KITin CBF AML	1	100.0		100.0
CEBPA	2	100.0		100.0
Others	20	30.9		30.7
Previous transplant
No	15	26.8	0.382	25.7	0.511	1.557 (0.584–4.150)
Yes	12	43.8	0.382	41.7	0.511	1.557 (0.584–4.150)

Abbreviations: BM, bone marrow; CBF, core-binding factor; EFS, event-free survival; EM, extramedullary; OS, overall survival; FG, favorable prognosis group; IG, intermediate prognosis group; PG, poor prognosis group..

Table 3 . Multivariate analysis of prognostic factors affecting survival..

	Odds ratio	95% CI	P
Interval from diagnosis to first relapse	2.799	0.763–10.267	0.121
Remission after 1 course of reinduction	16.674	3.490–79.658	0.001
Prognostic group	1.199	0.227–6.339	0.831