Treatments for children and adolescents with AML

Hyery Kim

doi:10.5045/br.2020.S002

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Blood Res 2020; 55(S1):

Published online July 31, 2020

https://doi.org/10.5045/br.2020.S002

Treatments for children and adolescents with AML

Hyery Kim

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Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul, Korea

Correspondence to : Hyery Kim, M.D., Ph.D.
Division of Pediatric Hematology/ Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 88-1 Olympic-ro 43-gil, Songpa-gu, Seoul 105505, Korea
E-mail: taban@hanmail.net

Received: November 26, 2019; Revised: January 30, 2020; Accepted: February 14, 2020

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

In recent decades, survival rates for childhood acute myeloid leukemia have remarkably improved, owing to chemotherapy intensification, allogeneic hematopoietic stem cell transplantation, and improved supportive care. Furthermore, treatment protocols have evolved and are currently better matched to prognostic factors and treatment responses. Recently, new molecular prognostic factors were discovered via leukemia genomic studies. Moreover, new tumor subtypes with independent gene expression profiles have been characterized. To broaden the therapeutic options for patients with poor prognoses, therapies that target specific candidate mutations are being identified. Additionally, new drugs are undergoing clinical trials, and immunotherapy is attracting significant interest as a treatment option for recurrent or refractory childhood acute myeloid leukemia.

Keywords Childhood, Adolescents, Acute myeloid leukemia, Treatment, Prognosis, Survival

Article

Review Article

Blood Res 2020; 55(S1): S5-S13

Published online July 31, 2020 https://doi.org/10.5045/br.2020.S002

Treatments for children and adolescents with AML

Hyery Kim

Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul, Korea

Correspondence to:Hyery Kim, M.D., Ph.D.
Division of Pediatric Hematology/ Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 88-1 Olympic-ro 43-gil, Songpa-gu, Seoul 105505, Korea
E-mail: taban@hanmail.net

Received: November 26, 2019; Revised: January 30, 2020; Accepted: February 14, 2020

Abstract

Keywords: Childhood, Adolescents, Acute myeloid leukemia, Treatment, Prognosis, Survival

Abstract

Table 1 . Genetic prognostic markers in international prospective clinical trials of pediatric patients with acute myeloid leukemia..

Study group (protocol no.)	Unfavorable prognostic markers	Favorable prognostic markers
Children’s Oncology Group (AAML1831)	inv(3)(q21q26.3)–MECOM-RPN1 fusion	t(8;21)(q22;q22) RUNX1-RUNX1T1
	t(6;9)(p23;q34.1)(DEKDEK-NUP214)	inv(16)/t(16;16)(p13.1q22) CBFB-MYH11
	Monosomy 7	NPM1 mutations
	Monosomy 5/5q	Biallelic CEBPA mutation
	Monosomy 5/5q-[EGR1(5q31)deleted]
	KMT2A(MLL)(11q23.3)
	-t(4;11)(q21;q23)
	-t(6;11)(q27;q23)
	-t(10;11)(p11.2;q23)
	-t(10;11)(p12;q23)
	-t(11;19)(q23;p13.3)
	NUP98(11p15.5)
	12p: Rearrangement or loss of ETV6
	t(16;21)(p11;q22)(FUS-ERG)
	FLT3/ITD+with allelic ratio>0.1%
	CBFA2T3-GLIS2
	RAM phenotype
	KAT6A (8p11.21) Fusion (10p12)(for patients who are 90 days or older)
	Non-KMT2A-MLLT10 Fusions
St. Jude Children’s Hospital (AML16)	DEK-NUP214 [t(6;9)]	Absence of high-risk features
	KAT6A-CREBBP [t(8;16)]
	RUNX1-CBFA2T3 [t(16;21)]
	-7, -5, 5q-, KMT2A-MLLT10 [t(6;11)]
	KMT2A-MLLT4 [t(10;11)]
	inv(3)(q21q26.2)
	CBFA2T3-GLIS2 [inv(16)(p13.3q24.3)]
	NUP98-KDM5A [t(11;12)(p15;p13)]
	ETV6-HLXB [t(7;12)(q36;p13)]
	NUP98-HOXA9 [t(7;11)(p15.4;p15)]
	NUP98-NSD1
	FLT3-ITD in combination with either NUP98-NSD1 fusion or WT1 mutation
	Acute megakaryoblastic leukemia with KMT2Arearrangements, CBFA2T3-GLIS2[inv(16)(p13.3q24.3)], or NUP98-KDM5A[t(11;12)(p15;p13)]
Berlin-Frankfurt-Münster	Complex karyotype	t(8;21)
	-5	inv(16)
	del(5q)-7
	Abnormalities of 3q
	FLT3 mutation
United Kingdom Medical Research Council (AML MRC 17)	Complex karyotype	t(8;21)/AML1-ETO
	-5	inv(16)/t(16;16)/CBFB-MYH11
	del(5q)-7
	Abnormalities of 3q
	FLT3 mutation

Table 2 . Recent publications on relapsed or refractory pediatric patients with acute myeloid leukemia..

Reference	Drugs	Response (No. of patients)
Niktoreh et al. 2019 [59]	Gemtuzumab ozogamicin±other chemotherapeutic agents	51% (36/71)
Cooper et al. 2019 [60]	CPX-351 (a liposomal preparation of cytarabine and daunorubicin)	81% (30/37) CR/CRp/CRi
van Eijkelenburg et al. 2018 [61]	Clofarabine, liposomal daunorubicin, high-dose cytarabine	68% (21/31) CR/CRi/PR
Messinger et al. 2017 [62]	Clofarabine, cyclophosphamide, and etoposide	51% (9/17) CR/CRp/CRi
Cooper et al. 2017 [63]	Plerixafor, high dose cytarabine, etoposide	23% (3/13) CR/CRp/CRi
Horton et al. 2014 [64]	Bortezomib, low-dose cytarabine, idarubicin	57.1% (8/14) CR/CRp/CRi (cycle 1)
Horton et al. 2014 [64]	Bortezomib, high-dose cytarabine, etoposide	47.8% (11/23) CR/CRp/CRi (cycle 1)
Cooper et al. 2014 [57]	Clofarabine, cytarabine	45% (21/47) CR/CRp
Shukla et al. 2014 [56]	Clofarabine, topotecan, vinorelbine, thiotepa	67% (8/12)
Kaspers et al. 2013 [55]	FLAG	59% (117/197)
Kaspers et al. 2013 [55]	FLAG+liposomal daunorubicin	69% (135/197)
Miano et al. 2012 [58]	Clofarabine, etoposide, cyclophosphamide	44% (7/16) CR/CRi
Inaba et al. 2011 [65]	Clofarabine, cytarabine, daily sorafenib	72% (8/11) CR/CRi
Inaba et al. 2010 [66]	Cladribine, topotecan	35% (9/26)

Abbreviations: CR, complete remission; CRi, complete remission with incomplete count recovery; CRp, notable CR with incomplete platelet recovery; FLAG, fludarabine, high dose cytarabine, filgrastim..