Mutated WT1, FLT3-ITD, and NUP98-NSD1 Fusion in Various Combinations Define a Poor Prognostic Group in Pediatric Acute Myeloid Leukemia

Table 1

Patient Characteristics.

FEATURES		All patients		WT1 wild-type		WT1 mutated			FLT3-ITD neg.		FLT3-ITD pos.
		n	%	n	%	n	%	p	n	%	n	%	p
Study Population
Number ()		353	100	305	100	48	100		301	100	52	100
Age (years), median (range)		9.09		7.97		10.68		0.03	7.8		12.95		0.0001
		(0 -18)		(0 - 18)		(0.8 - 17.8)			(0 -18)		(2.7 - 17.9)
Gender
male		183	52%	159	52%	24	50%	0.783	153	51%	30	58%	0.36
female		170	48%	146	48%	24	50%		148	49%	22	42%
WBC count at diagnosis
median x 10^9 cells/L; (range)		24.5		24		42.85		0.1	20.1		73.5		0.0001
		(0.019 - 475)		(0.23 - 475)		(0.019 - 324)			(0.019-475)		(1.8 - 324)
Morphological Classification
FAB	M0	9	3%	7	2%	2	4%		5	2%	4	8%
	M1/M2	134	38%	107	35%	27	56%		100	33%	34	65%
	M4Eo+	31	9%	27	9%	4	8%		29	10%	2	4%
	M4Eo-/M5	132	37%	125	41%	7	15%	0.008	121	40%	11	21%	0.0001
	M6	3	1%	2	1%	1	2%		3	1%	0	0%
	M7	22	6%	21	7%	1	2%		22	7%	0	0%
	AUL/other	22	6%	16	5%	6	13%		21	7%	1	2%
Cytogenetics
	t(8;21)	38	11%	38	12%	4	8%		36	12%	2	4%
	inv(16)	32	9%	28	9%	0	0%		31	10%	1	2%
	MLL rearr.	61	17%	60	20%	1	2%	<0.0001	60	20%	1	2%	0.0001
	others	117	33%	99	32%	18	38%		97	32%	20	38%
	normal	97	27%	72	24%	25	52%		69	23%	28	54%
	no data	8	2%	8	3%	0	0%		8	3%	0	0%
NUP98-NSD1
	positive	15	4%	7	2%	8	17%	<0.0001	6	2%	9	17%	<0.0001
	negative	231	65%	198	65%	33	69%		197	65%	34	65%
	no data	107	30%	100	33%	7	15%		98	33%	9	17%
Co-mutations
FLT3-ITD	negative	301	85%	272	89%	29	60%	<0.0001
	positive	52	15%	33	11%	19	40%
WT1	wildtype	305	86%						272	90%	33	63%	0.0001
	mutated	48	14%						29	10%	19	37%
NPM1	wildtype	316	90%	273	90%	43	90%		277	92%	39	75%
	mutated	31	9%	26	9%	5	10%	0.69	20	7%	11	21%	0.0004
	no data	6	2%	6	2%	0	0%		4	1%	2	4%
nRAS	wildtype	282	80%	245	80%	37	77%		235	78%	47	90%
	mutated	59	17%	48	16%	11	23%	0.26	57	19%	2	4%	0.008
	no data	12	3%	12	4%	0	0%		9	3%	3	6%
KIT	wildtype	308	87%	267	88%	41	85%	0.51	266	88%	42	81%	0.31
	mutated	41	12%	34	11%	7	15%		33	11%	8	15%
	no data	4	1%	4	1%	0	0%		2	1%	2	4%
CEBPA	wildtype	163	46%	121	40%	42	88%	<0.0001	122	41%	41	79%	<0.0001
	single	6	2%	4	1%	2	4%		6	2%	0	0%
	double	10	3%	9	3%	1	2%		8	3%	2	4%
	no data	174	49%	174	57%	0	0%		165	55%	9	17%
HSCT
HSCT in 1ts CR		64	18%	56	18%	8	17%	0.78	53	18%	11	21%	0.54
Chemotherapy only		289	82%	249	82%	40	83%		248	82%	41	79%
Patient Status
	alive	251	71%	221	72%	30	63%		225	75%	26	50%
	deceased	73	21%	58	19%	15	31%	0.14	51	17%	22	42%	0.0001
	LFU	29	8%	26	9%	3	6%		25	8%	4	8%

n, number; WT1, Wilms tumor 1; FLT3-ITD, fms related tyrosine kinase 3-internal tandem duplication; WBC, white blood cell; FAB, French-American-British; M4Eo+, AML M4 subtype with the presence of atypical eosinophils; M4Eo-, AML M4 subtype without the presence of atypical eosinophils; AUL, acute undifferentiated leukemia; t, translocation; inv, inversion; MLL rear., rearrangement of MLL gene; NUP98-NSD1, Nucleoporin-Nuclear Receptor Binding SET Domain Protein 1 fusion gene; NPM1, nucleophosmin 1; NRAS, neuroblastoma RAS viral oncogene homolog; c-KIT, KIT proto-oncogene; CEBPA, CCAAT/enhancer binding protein (C/EBP) alpha; HSCT, hematopoietic stem cell transplantation; CR, complete remission; HSCT, hematopoietic stem cell transplantation; LFU, lost to follow-up. p-values derived from Pearson’s Chi-squares test.