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Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children's Oncology Group and SWOG

Phoenix A. Ho, Kenneth J. Kopecky, Todd A. Alonzo, Robert B. Gerbing, Kristen L. Miller, Julia Kuhn, Rong Zeng, Rhonda E. Ries, Susana C. Raimondi, Betsy A. Hirsch, Vivian Oehler, Craig A. Hurwitz, Janet L. Franklin, Alan S. Gamis, Stephen H. Petersdorf, Jeanne E. Anderson, John E. Godwin, Gregory H. Reaman, Cheryl L. Willman, Irwin D. Bernstein, Jerald P. Radich, Frederick R. Appelbaum, Derek L. Stirewalt and Soheil Meshinchi

Data supplements

Article Figures & Data

Figures

  • Figure 1

    Distribution of FLT3/ITD within cytogenetic groups by IDH1 SNP status in adult AML. FLT3/ITD was present in 90% of SNP-positive adult AML patients with normal karyotype; conversely, FLT3/ITD was present in only 9% of SNP-positive adult AML patients with cytogenetic abnormalities.

  • Figure 2

    Prognostic significance of IDH1 SNP rs11554137 in adult and pediatric AML patients. Kaplan-Meier estimates of (A) OS and (B) RFS for adult (SWOG) and pediatric (COG) patients with or without SNP rs11554137. RFS was significantly worse in SNP-positive adult patients (P = .0014).

  • Figure 3

    OS and RFS stratified by risk group and IDH1 SNP status in 186 adult AML patients. Kaplan-Meier estimates of (A) OS and (B) RFS are shown by risk group and, within the adverse risk group, IDH1 SNP status. Tick marks indicate censored observations. Among adult patients with adverse risk based on karyotype or FLT3/ITD, the IDH1 SNP was not significantly associated with OS (P = .94) or RFS (P = .28).

Tables

  • Table 1

    Characteristics of adult and pediatric AML patients by SNP status

    CharacteristicPediatric AMLCharacteristicAdult AML
    IDH1 SNP+ (n = 27)IDH1 SNP (n = 226)PIDH1 SNP+ (n = 30)IDH1 SNP (n = 244)P
    N%N%N%N%
    SexSex
        Male176312354.399    Male113713756.052
        Female103710346    Female196310744
    Age, yAge, y
        Median (range)5.8(0.15-17.2)10.4(0.07-21.6).046*    Median (range)63(22-76)63(18-88).59
        0-2 y12445123    18-55 y11377129
        3-10 y6226931    56-67 y11378334
        > 11 y93310647     > 68 y8279037
    Race.55Race.0039*
        White186915777    White206721789
        Black6233015    Black930177
        Asian28126    Asian0073
        Other0063    Other0010
        Unknown121    Unknown1321.00
    Ethnicity.19Ethnicity.21
        Hispanic284018    Hispanic2762
        Non-Hispanic239217782    Non-Hispanic289323898
        Unknown29    Unknown00
    WBC, × 109/L, median (range)33.2(0.98-495)19.6(0.8-409).240WBC, × 109/L, median (range)26.5(2.7-298)29.8(0.7-274).82
    BM blasts, %, median (range)72(22-97)68(0-100).596BM blasts, %, median (range)80(8-97)70(0-99).025*
    CytogeneticsCytogenetics
        Normal3134421.426    Normal11467642.83
        t(8;21)282713.747    CBF002212.083
        Abnormal 165212613.336    −7/7q−14158.7
        Abnormal 113134622.274    +8142715.21
        t(6;9)(p23;q34)00731.000    Other11464022.022*
        −7/7q−2873.236    No data665
        −5/5q−00311.000
        +814199.703FLT3/ITD
        Other8332914.033*    Present13487533.140
        No data318    Absent145215167
    318
    FLT3/ITDFLT3/ITD by karyotype
        Present4152511.527    Normal
        Absent238520189        Present9902941.0053*
        Unknown00        Absent1104159
        Abnormal
            Present1912131.00
            Absent10918386
    NPM1 mutationNPM1 mutation
        Present00105.604    Present9357032.823
        Absent2310019195    Absent176515168
        Unknown425    Unknown423
    CEBPA mutationCEBPA mutation
        Yes27105.629    Yes00631.000
        No259320695    No2810021797
        Unknown010    Unknown221
    • * Significant P value.

    • CBF abnormality includes t(8;21), inv(16), and t(16;16). Three patients with +8 also have CBF abnormalities, and another 3 have −7/7q−.

    • Two patients with −7/7q− also have +8; another 2 patients with −7/7q− also have t(8;21); and a fifth patient with −7 also has der(8)t(8;21)(q12;p11) as part of a complex karyotype.

  • Table 2

    Distribution of adult AML patients in risk categories by IDH1 SNP status

    IDH1 SNP+ (n = 21)IDH1 SNP (n = 165)
    N%N%
    Favorable risk
        CBF AML002012
        CN, FLT3154125
    Adverse risk
        CN, FLT3+9432918
        Any other cytogenetics11527545