Advertisement

Excellent long-term survival of children with Down syndrome and standard-risk ALL: a report from the Children’s Oncology Group

Yousif Matloub, Karen R. Rabin, Lingyun Ji, Meenakshi Devidas, Johann Hitzler, Xinxin Xu, Bruce C. Bostrom, Linda C. Stork, Naomi Winick, Julie M. Gastier-Foster, Nyla A. Heerema, Eileen Stonerock, William L. Carroll, Stephen P. Hunger and Paul S. Gaynon

Data supplements

Article Figures & Data

Figures

Tables

  • Table 1.

    Interim maintenance regimens

    Oral methotrexate regimenIV methotrexate regimen
    Vincristine: 1.5 mg/m2 days 0 and 28Vincristine: 1.5 mg/m2 (maximum, 2 mg) every 10 d × 5
    Dexamethasone: PO 6 mg/m2/d days 0-4 and days 28-32Methotrexate: initial dose: 100 mg/m2 escalate by 50 mg/m2 per toxicity parameters every 10 d × 5
    Methotrexate: PO 20 mg/m2 weekly × 8Methotrexate intrathecal day 30
    Mercaptopurine: PO 75 mg/m2/d days 0-49
    Methotrexate: intrathecal day 28
  • Table 2.

    Characteristics of randomized patients with and without DS

    DSTotal DS, n = 75Non-DS, n = 2003P*
    PO MTX, n = 44IV MTX, n = 31P*
    Age at diagnosis, y
     <220.332184.07
     2-53220521393
     6-9101121426
    Sex
     Female2413.28371110.30
     Male201838893
    WBC
     <20 × 109/L3629.18651659.39
     ≥20 × 109/L8210343
     Unknown/missing0001
    CNS status
     CNS-13927.64661772.99
     CNS-221399
     CNS-30005
     Unknown/missing336127
    Cytogenetics
     ETV6-RUNX110.991357<.001
     Double trisomies 4 and 1051.396244.27
    BM day 7
     M12818.6446900.016
     M26713599
     M38614424
     Uninterpretable20235
     Not done/missing00045
    BM day 14
     M11813311065.99
     M200031
     M30000
     Uninterpretable0001
     Not done/missing261844905
    • —, not calculated.

    • * The χ2 or Fisher's exact test was used after excluding unknown/missing/uninterpretable/not done groups.

    • Patients (n = 1041) were analyzed for the presence of ETV6-RUNX1 transcript.

    • Patients (n = 1330) were analyzed for the presence of trisomies 4 and 10.

  • Table 3.

    Distribution of events in the randomized patients with and without DS

    Event typesPO MTXIV MTXSDIDDI
    DS (n = 44)Non-DS (n = 992)DS (n = 31)Non-DS (n = 1011)DS (n = 42)Non-DS (n = 993)DS (n = 33)Non-DS (n = 1010)
    Event-free36876299243789528905
    iBM54560344261
    iCNS27112216
    BM + CNS125107
    BM + testicular14113
    BM + other14311
    CNS + other1111
    Testicular9164
    Other relapse5142
    Second malignant neoplasm182146
    Death as first event15121314
    Total events81162875985105
    • —, not calculated; iBM, isolated BM relapse; iCNS, isolated CNS relapse.

  • Table 4.

    Comparison of incidence of grades 3/4 nonhematological toxicities among randomized patients with and without DS

    Induction DS/non-DS, %PConsolidation DS/non-DS, %PIM-1 DS/ non-DS, %PDI-1 DS/ non-DS, %PIM-2 DS/ non-DS, %PDI-2 DS/ non-DS, %PMaintenance DS/non-DS, %P
    Cardiovascular2.7/5.0.651.3/1.2.882.7/0.6.0321.4/1.1.800/00/1.2.563.0/0.8.045
    Coagulation5.3/6.0.470/0.5.541.4/0.1.0020/1.7.260/00/1.7.781.5/0.5.25
    Gastrointestinal*4.0/5.8.566.7/4.0.4816.2/3.6<.00116.4/7.0.00720.3/4.2<.00117.9/7.7.1315.2/6.7.027
    Hepatic10.7/7.2.5216.0/10.8.1716.2/12.9.389.6/4.8.07810.1/11.7.923.6/6.0.8425.8/31.2.14
    Infection/febrile neutropenia14.7/15.3.8418.7/9.9.01412.2/8.3.4628.8/23.9.4311.6/8.5.3732.1/26.4.7350.0/42.1.26
    Neurology2.7/5.1.606.7/4.2.194.1/3.6.881.4/2.9.732.9/1.9.827.1/3.0.367.6/3.8.18
    Renal/genitourinary0/0.5.830/0.4.880/0.1.850/0.2.950/0.1.850/0.2.810/0.3.64
    • —, not calculated.

    • * Differences in incidence mainly due to mucositis.

  • Table 5.

    Comparison of incidence of selected nonhematological toxicities among patients with and without DS randomized to MTX regimens

    PO MTXIV MTXDS patientsNon-DS patients
    DS, %Non-DS, %PDS, %Non-DS, %PPO, %IV, %PPO, %IV, %P
    ALT (grades 3/4)
     IM #116.317.1.7012.97.6.4816.312.9.6917.17.6<.001
     IM #27.513.9.406.98.6.847.56.9.6613.98.6.001
    Infection with neutropenia (grades 3/4)
     IM #14.72.6.4302.3.394.70.222.62.3.66
     IM #25.03.9.7201.5.5150.223.91.5.001
    Leukoencephalopathy (all grades)
     IM #100.2.9600.4.94000.20.4.61
     IM #200.1.8400.5.93000.10.5.25
    Mucositis (grades 3/4)
     IM #12.30.6.3029.03.4<.0012.329.0.0040.63.4<.001
     IM #2100.6<.00127.64.1<.0011027.6.130.64.1<.001
    Seizures (all grades)
     IM #100.1.833.21.2.5503.2.240.11.2.02
     IM #200.1.8400.8.89000.10.8.05
    • —, not calculated; ALT, alanine aminotransferase.