Prognostic factors in infants with acute myeloid leukemia

Abstract

Little is known about the factors that affect treatment outcome in very young children with acute myeloid leukemia (AML). We therefore analyzed the prognostic impact of various presenting clinical and laboratory features by discrete age group in 299 children with AML treated in four consecutive clinical trials between 1980 and 1997. Differences in presenting features, as well as treatment outcome, were compared between children aged 12 months or less (n = 28) or 13 to 24 months (n = 28) and those more than 24 months of age (n = 243). Children in the two youngest groups (24 months of age or less) had similar presenting features and treatment outcome. Collectively, these 56 children were significantly more likely than the 243 older patients to have M4 or M5 leukemia (70% vs 30%), CNS leukemia (33% vs 22%), the t(9;11) (p22;q23) (18% vs 6%) or other 11q23 translocations (23% vs 3%), and less likely to have Auer rods (2% vs 54%) or the t(8;21) (q22;q22) (0% vs 17%). Among patients aged 24 months or less, two factors independently predicted a favorable prognosis: FAB M4 or M5 leukemia (relative risk of relapse, 0.4; 95% confidence interval, 0.2-0.9) and the t(9;11) (relative risk, 0.3; 95% confidence interval , 0.1-1.0). Leukocyte count and 11q23 translocations other than the t(9;11) lacked prognostic significance. Among older patients, a leukocyte count Ͻ50 × 10 9 /l and the presence of the t(9;11) conferred a favorable prognosis. Leukemia (2000) 14, 684-687.

True

“…Our data on infant AML and the data previously reported in infant ALL and AML showed that some infant leukemias with a normal karyotype or chromosome abnormalities other than 11q23 translocations had MLL rearrangements (Tables 1 and 2). These findings may explain the higher incidence of the 11q23/MLL rearrangements in the present series and the series of infant AML reported by Hilden et al 9 or Martinez-Climent et al 23 than in that reported by Pui et al 7 The great majority of AML infants with 11q23/MLL rearrangements in the present series had M4 or M5 type, and a similar association has been reported in adult as well as infant AML with 11q23/MLL rearrangements. 24,25 While t(4;11)(q21;q23) or t(11;19)(q23;p13.3) predominated in infant ALL with 11q23/MLL rearrangements, [4][5][6]8 none of the 11q23 translocations reported for the present series or the previously reported series seemed to predominate in infant and adult AML with 11q23/MLL rearrangements.…”

“…2,3 Several investigators have reported that 11q23/MLL rearrangements are frequent (70-80%) in infant acute lymphoblastic leukemia (ALL), and unequivocally predict a poor clinical outcome. [4][5][6][7][8] Acute myeloid leukemia (AML) is less common than ALL in infants, and only two series of infant AML have previously evaluated frequency and prognostic implication of 11q23/MLL rearrangements. 7,9 Recurrent chromosome translocations other than 11q23 translocations in infant AML include t(1;22)(p13;q13) and t(8;16)(p11;p13), which are associated with AML, M7 and AML, M4/M5, respectively.…”

“…[4][5][6][7][8] Acute myeloid leukemia (AML) is less common than ALL in infants, and only two series of infant AML have previously evaluated frequency and prognostic implication of 11q23/MLL rearrangements. 7,9 Recurrent chromosome translocations other than 11q23 translocations in infant AML include t(1;22)(p13;q13) and t(8;16)(p11;p13), which are associated with AML, M7 and AML, M4/M5, respectively. 10,11 No other recurrent translocations have formerly been identified in infant AML.…”

True

“…Most infant patients with ALL are near-diploid (45-47 chromosomes) with structural abnormalities and a high frequency of 11q23 rearrangements, and very few have the high hyperdiploidy (Ͼ50 chromosomes) associated with a good prognosis. Moreover, infants with ALL have a poor prognosis compared with ALL in children у1 year of age at diagnosis, and much of the poor outcome has been attributed to a breakpoint in chromosomal band 11q23, [1][2][3][4][5] which occurs in approximately 50% of infants with ALL studied by cytogenetic analyses 1,[6][7][8] and approximately 75% studied by molecular techniques. 4,6,[8][9][10][11] Although deletions, inversions and unbalanced translocations are found, the 11q23 breakpoint usually occurs as part of a reciprocal translocation, with many different 11q23 partner chromosomes described, the most common being t(4;11)(q21;q23), occurring in 30-45% of infants when studied by chromosomal analysis.…”

“…4,6,[8][9][10][11] Although deletions, inversions and unbalanced translocations are found, the 11q23 breakpoint usually occurs as part of a reciprocal translocation, with many different 11q23 partner chromosomes described, the most common being t(4;11)(q21;q23), occurring in 30-45% of infants when studied by chromosomal analysis. 1,3,5 Both cytogenetic and molecular analyses have been used to determine the presence and prognostic significance of 11q23 aberrations in infant ALL. Molecular studies of MLL, the gene involved in most 11q23 rearrangements, 4 show that approximately 70% of infants have rearranged MLL and that abnormal MLL correlates with a poor outcome.…”