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Letters to the Editor
The clinical and biological characteristics of
NUP98-KDM5A pediatric acute myeloid leukemia
Pediatric acute myeloid leukemia (AML) is a rare, het- erogeneous disease, characterized by recurrent cytoge- netic and molecular aberrations.1,2 Genetic aberrations are the most important prognostic factor, besides early response to treatment.3,4 In pediatric AML, improvement of clinical outcome has reached a plateau, despite inten- sive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) in selected cases, leading to event-free survival rates of approximately 55-60% in the current era.1,2,5 Hence, identification of prognostic sub- groups is important for risk-group stratification.1,5 Furthermore, novel therapeutic options should be explored for pediatric AML, with the objective of improv- ing survival especially for patients with high-risk sub- types, such as those with the NUP98-NSD1 rearrange- ment (NUP98-KDM5A+).6,7
Here, we present the results of a collaborative study between the Children’s Oncology Group (COG) and European AML study groups, aimed to define the biolog- ical and clinical characteristics of AML patients carrying NUP98-KDM5A outside acute megakaryoblastic leukemia. The methodology and analysis are described in detail in the Online Supplementary Methods. In total 2,393 patients were included from various trials by the COG, AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica), BFM (Berlin-Frankfurt-Münster) group, CPH (Czech Pediatric Hematology Working Group), DCOG (Dutch Childhood Oncology Group) and LAME (Leucémie Aiquë Myéloblastique Enfant). NUP98- KDM5A rearrangements were detected in 47/2,393 pedi- atric AML cases (2.0%) with similar prevalence in the COG and European cohorts (Table 1). The median age of the NUP98-KDM5A+ patients was significantly lower than that of patients without this fusion gene (3.2 vs. 9.4 years; P=0.001) (Table 1, Online Supplementary Figure S1A). The median white blood cell count of NUP98-
Table 1. Clinical characteristics of pediatric patients with or without NUP98-KDM5A rearrangements.
Characteristic
Total, n.
Group
COG (03p1/0531/1031), n (%)
European, n (%) Gender
Male, n (%) Female, n (%) Unknown, n
Median age at diagnosis, years (range)
Unknown, n
Median WBC x109/L (range) FAB type, n (%)
NUP98-KDM5A+ 47
36 (77)
11 (23)
24 (53)
21 (47)
2
3.2 (0.07-18.5) 2
11.7 (1.8-237.3)
NUP98-KDM5A – 2346
2003 (85)
343 (15)
1215 (52) 1114 (48) 17
9.4 (0-29.8) 13
23.9 (0.2-2730)
P
0.093
0.877
0.001
0.006
0.617 0.568 0.017 0.026 0.911 <0.001 <0.001 1.000
1.000
0.885
0.005 <0.001 0.002 0.001 0.913
M0 1(3) 41(3)
M1
M2
M4
M5
M6
M7
Other
Not otherwise specified
Treatment response
CR obtained, n (%) Refractory disease, n (%) Unknown, n
HSCT in CR1
5-year survival, % (2SE)
Event-free survival Overall survival Relapse risk Relapse-free survival
Transplant-related mortality
2 (7) 1 (3) 2 (7) 6 (21) 5 (17) 10 (34) 2 (7) 18*
41 (91) 4 (9) 2
7 (15)
29.6 (14.6) 34.1 (16.1) 62.6 (16.7) 32.5 (15.7) 4.9 (6.8)
161 (13) 280 (22) 317 (25) 275 (22) 16 (1) 99 (8) 87 (7) 1070*
2011 (90) 224 (10) 111 332 (14)
47.0 (2.1) 63.7 (2.1) 42.5 (2.3) 51.6 (2.1) 5.9 (1.1)
630
*The AAML1031 study did not collect data on FAB types; however, we were able to determine acute megakaryoblastic leukemia status for AAML1031 patients according totheWorldHealthOrganizationcriteria.COG:Children’sOncologyGroup;WBC:whitebloodcellcount;FAB:FrenchAmericanBritishmorphologyclassification;CR:com- plete remission; HSCT: hematopoietic stem cell transplant; CR1: first complete remission; SE, standard error.
haematologica | 2021; 106(2)