Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Sujin Choi; Bo Kyung Kim; Hong Yul Ahn; Kyung Taek Hong; Jung Yoon Choi; Hee Young Shin; Hyoung Jin Kang

doi:10.5045/br.2020.2020127

Quick links

Most Cited Most Read Ahead of Print Archives Go to E-submission

Original Article

Split Viewer

Blood Res 2020; 55(4):

Published online December 31, 2020

https://doi.org/10.5045/br.2020.2020127

Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Sujin Choi¹, Bo Kyung Kim^1,2, Hong Yul Ahn^1,2, Kyung Taek Hong^1,2, Jung Yoon Choi^1,2, Hee Young Shin^1,2, Hyoung Jin Kang^1,2,3

Author Info. +

¹Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, ²Seoul National University Cancer Research Institute, Seoul, ³Wide River Institute of Immunology, Hongcheon, Korea

Correspondence to : Hyoung Jin Kang, M.D., Ph.D.
Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
E-mail: kanghj@snu.ac.kr

Received: June 4, 2020; Revised: September 29, 2020; Accepted: October 16, 2020

Abstract

Go to

Abstract

Background
Acute myeloid leukemia (AML) with internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with poor outcomes. This study aimed to analyze the outcomes of pediatric AML patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era.
Methods
We retrospectively reviewed and identified 18 patients diagnosed with non-M3 AML with FLT3-ITD mutations at Seoul National University Children’s Hospital between May 2008 and August 2019.
Results
The median age was 13 years (range, 6-19 yr). The median follow-up time was 43 months (range, 6-157 mo). Fourteen patients received BH-AC-based (N4-Behenoy1-1-b-D-arabinofuranosy1cytosine) and 4 received cytarabine-based induction chemotherapy. Complete remission (CR) was achieved in 72.2% of the patients after the first induction chemotherapy and 80% of the patients achieved CR after salvage therapy. The overall CR rate was 94% (17/18 patients). These 17 patients underwent hematopoietic stem cell transplantation (9 matched unrelated donors, 5 matched related donors, and 3 haploidentical donors). Relapse occurred in 22% of the patients. Event free survival and overall survival rates were 53.8±12.1% and 53.6±12.1%, respectively, and they were not significantly different according to the type of induction chemotherapy (P=0.690) or the type of donor (P=0.102).
Conclusion
This study outlines the outcomes of pediatric AML patients with FLT3-ITD-mutations in one institution over a decade. Outcomes were significantly improved in this study compared to our previous report in 2004, where RFS and EFS were 0%. This study can provide baseline data for pediatric patients in the pre-FLT3 inhibitor era.

Keywords FLT3-ITD, Acute myeloid leukemia, Pediatric, Overall survival

Article

Original Article

Blood Res 2020; 55(4): 217-224

Published online December 31, 2020 https://doi.org/10.5045/br.2020.2020127

Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Sujin Choi¹, Bo Kyung Kim^1,2, Hong Yul Ahn^1,2, Kyung Taek Hong^1,2, Jung Yoon Choi^1,2, Hee Young Shin^1,2, Hyoung Jin Kang^1,2,3

Correspondence to:Hyoung Jin Kang, M.D., Ph.D.
Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
E-mail: kanghj@snu.ac.kr

Received: June 4, 2020; Revised: September 29, 2020; Accepted: October 16, 2020

Abstract

Keywords: FLT3-ITD, Acute myeloid leukemia, Pediatric, Overall survival

Abstract

Fig 1.

Download

Figure 1.Treatment and outcome of patients. ^a)Enocitabine, idarubicin, intrathecal cytarabine; ^b)cytarabine, idarubicin, mitoxantrone.Abbreviations: AML, acute myeloid leukemia; CR, complete remission; DOD, died of disease; HSCT, hematopoietic stem cell transplant; MRD, matched related donor; MUD, matched unrelated donor; N, number; NED, no evidence of disease; TRM, treatment-related mortality.

Blood Research 2020; 55: 217-224https://doi.org/10.5045/br.2020.2020127

Fig 2.

Download

Figure 2.Patients’ overall survival (OS) and event free survival (EFS).
Abbreviations: Haplo, haploidentical; HSCT, hematopoietic stem cell transplant; MRD, matched related donor; MUD, matched unrelated donor.

Blood Research 2020; 55: 217-224https://doi.org/10.5045/br.2020.2020127

Table 1 . Characteristics of patients with FLT3 mutations..

N	18
Median age at diagnosis	13 (6–19)
Gender (N) F:M	11:7
Prognostic factors (%)
Primary refractory	5 (27.8)
High WBC counta)	4 (22.2)
Secondary AML	2 (11.1)
FAB (N, %)
M1	7 (38.9)
M2	4 (22.2)
M4	6 (33.3)
M5	1 (5.5)
Cytogenetic/molecular (N, %)
Normal	9 (50)
inv (16)	0
KMT2A/MLL	1 (5.5)
PML/RARA	0
AML1/ETO	3 (16.7)
FLT/TKD	1 (5.5)
Induction chemotherapy (N, %)
BH-AC-basedb)	14 (77.7)
Cytarabine-basedc)	4 (22.2)
HSCT (N, %)	17 (94.4)
MUD	9 (52.9)
MRD	5 (27.8)
Haploidentical	3 (16.7)

^a)WBC count of >100×10⁹/L at diagnosis; ^b)enocitabine, idarubicin, intrathecal cytarabine; ^c)cytarabine, idarubicin, mitoxantrone..

Abbreviations: AML, acute myeloid leukemia; CR, complete remission; DOD, died of disease; FAB, French-American-British classification; HSCT, hematopoietic stem cell transplant; MRD, matched related donor; MUD, matched unrelated donor; N, number; TRM, treatment-related mortality..

Table 2 . Characteristics and outcome of study patients (N=18)..

Pt. No.	Sex	Age (yr)	FAB	Cytogenetics at diagnosis	Combined molecularabnormalitya)	Induction	CRd)	HSCT donor type (HLA)	Dx to HSCT(M)	CR to HSCT(M)	Conditio-ning regimen	Engraft-ment (D)	HSCT Compli-cation	OS (entry to death, M)	Relapse (RFS, M)e)	HSCT to last follow up (M)	Outco-me
1	F	19	M4	46, XX		BH-ACb)	Yes	MUD(10/10)	7	5	TBIAcFluda	16	-	16	Yes (4)	9	DOD
2	M	11	M2	46,XY,t(5;21;8) (q13;q22;q22)/46,XY	AML1/ETO	BH-AC	Yes	MUD(9/10)	4	3	TBIAcFluda	14	skin aGVHDlung cGVHD	21	No	16	TRM
3	F	9	M2	49,XX,+8,+11,+18/46,XX		BH-AC	Yes	MUD(10/10)	7	6	TBIAcFluda	14	VOD, liver cGVHD	19	No	11	TRM
4	F	16	M4	46, XX		BH-AC	Yes	MUD(10/10)	7	6	TBIAcFluda	19	lung cGVHD	157	No	150	Alive
5	F	14	M4	46,XX,t(6;9)(p23;q34)46,XX,inv(1)(p13q21),t(6;9)(p23;q34)	DEK/NUP214	BH-AC	Yes	MUD(9/10)	5	4	TBIAcFluda	19	-	130	No	124	Alive
6	F	7	M5	46, XX		BH-AC	Yes	MUD(9/10)	3	2	BuFluVPATG	17	lung cGVHD	108	No	104	Alive
7	M	9	M1	46, XY		BH-AC	Yes	MRD	6	4	TBIAcFluda	12	-	13	Yes (4)	6	DOD
8	M	12	M1	46, XY		BH-AC	Yes	MRD	4	3	BuFluVPATG	11	VOD	106	No	102	Alive
9	F	10	M1	46,XX,t(7;11) (p15;p15)		BH-AC	Yes	MRD	4	3	BuFluVPATG	11	-	36	Yes (28)	32	TRM
10	F	15	M2	46,XX,t(8;21) (q22;q22)	AML1/ETO	BH-AC	Yes	MUD(10/10)	5	4	BuFluVPATG	11	-	106	No	100	Alive
11	M	18	M1	46,XY,t(6;9)(p23;q34)/46,XY	DEK/NUP214	BH-AC	Yes	MRD	5	4	BuFluVPATG	10	VOD, liver cGVHD	7	No	2	TRM
12	F	11	M1	46 XY		BH-AC	Yes	MRD	4	2	BuFluVPATG	10	VOD	32	Yes (12)	27	DOD
13	M	6	M4	46, XY	FLT3/TKD	BH-AC	Yes	MUD(10/10)	4	3	BuFluVPATG	11	VOD,lung cGVHD	101	No	96	Alive
14	F	13	M1	46,XX,16qh+		BH-AC	Yes	MUD(10/10)	4	1	BuFluVPATG	13	skin aGVHD	50	No	46	Alive
15	M	16	M2	45,X,-Y,t(8;21)(q22;q22)	AML1/ETO	Cytarabinec)	Yes	Haplo-identical	7	5	BuFluCy	20	-	73	No	66	Alive
16	F	13	M4	46,XX,t(11;19) (q23;p13.3)	MLL	Cytarabine	Yes	Haplo-identical	5	3	BuFluCy	18	-	70	No	65	Alive
17	M	16	M4	46, XY		Cytarabine	No	(-)	-	-	(-)	-	-	6	No	-	DOD
18	F	14	M1	46, XX	NPM1	Cytarabine	Yes	Haplo-identical	4	3	BuFluCy	16	-	13	No	9	Alive

^a)All patients were tested for FLT3/TKD, CBFB inv(16), AML1/ETO, MLL, and PML/RARA rearrangements at diagnosis. Other molecular abnormalities were tested in some patients only ^b)enocitabine, idarubicin, intrathecal cytarabine; ^c)cytarabine, idarubicin, mitoxantrone; ^d)CR including primary CR and CR after salvage therapies; ^e)months from end of therapy to relapse..

Abbreviations: aGVHD, acute graft versus host disease; BuFluCy, busulfan, fludarabine, cyclophosphamide; BuFluVPATG, Busulfan, etoposide, thymoglobulin, fludarabine; cGVHD, chronic graft versus host disease; CR, complete remission; DOD, died of disease; Dx, diagnosis; FAB, French–American–British classification; HSCT, hematopoietic stem cell transplant; MRD, matched related donor; MUD, matched unrelated donor; TBIAcFluda, TBI, AraC, thymoglobulin, fludarabine; TRM, treatment related mortality; VOD, veno-occlusive disease..

Volume 59 2024

Current Issue Archives

Article Tools

2.3

Original Article

Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Abstract

Article

Original Article

Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Abstract

Fig 1.

Fig 2.

Article Tools

Stats or Metrics

Share this article on

Related articles in BR

Treatment outcome and prognostic factors in relapsed pediatric acute myeloid leukemia

What is new in acute myeloid leukemia classification?

Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis