Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.
Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.
Balgobind
Brian V
BV
Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Raimondi
Susana C
SC
Harbott
Jochen
J
Zimmermann
Martin
M
Alonzo
Todd A
TA
Auvrignon
Anne
A
Beverloo
H Berna
HB
Chang
Myron
M
Creutzig
Ursula
U
Dworzak
Michael N
MN
Forestier
Erik
E
Gibson
Brenda
B
Hasle
Henrik
H
Harrison
Christine J
CJ
Heerema
Nyla A
NA
Kaspers
Gertjan J L
GJ
Leszl
Anna
A
Litvinko
Nathalia
N
Nigro
Luca Lo
LL
Morimoto
Akira
A
Perot
Christine
C
Pieters
Rob
R
Reinhardt
Dirk
D
Rubnitz
Jeffrey E
JE
Smith
Franklin O
FO
Stary
Jan
J
Stasevich
Irina
I
Strehl
Sabine
S
Taga
Takashi
T
Tomizawa
Daisuke
D
Webb
David
D
Zemanova
Zuzana
Z
Zwaan
C Michel
CM
van den Heuvel-Eibrink
Marry M
MM
D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D018572:Disease-Free Survival; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007390:International Agencies; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D014178:Translocation, Genetic
C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase