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Article Figures & Data

Figures

  • Fig. 1.

    Cumulative incidence of t-ML.

    The incidence of t-ML differed among the 14 patients who received radiation therapy (RT) and G-CSF, the 44 patients who received RT and no G-CSF, the 85 patients who received G-CSF but no RT, and the 269 patients who received neither G-CSF nor RT (P = .017). For those who did not receive RT (bottom left), there was a higher incidence (P = .0192) of t-ML top among those who did versus did not receive G-CSF (6-year estimates, 11.0% ± 3.5% versus 2.7% ± 1.3%). For those who did not receive G-CSF (bottom right), there was a higher incidence (P = .0038) of t-ML among those who received RT (6-year estimate, 12.3% ± 5.3%) than among those who did not receive RT (6-year estimate, 2.7% ± 1.3%).

Tables

  • Table 1.

    Induction and consolidation therapy Total XIIIA and XIIIB

    WindowMethotrexate (1 g/m2 or 30 mg/m2 every 6 h × 6), mercaptopurine (1 g/m2), or methotrexate plus mercaptopurine, day 137 38
    InductionPred (40 mg/m2/d), days 5–33
    VCR (1.5 mg/m2/wk × 4), days 5, 12, 19, and 26
    Daunorubicin (25 mg/m2), days 5 and 12
    Asparaginase (10 000 U/m2) start, day 5; thrice weekly × 2 weeks (3 weeks in those with poor early response)
    VP (300 mg/m2) + (AraC 300 mg/m2), days 27, 30, and 34
    XIIIA only: randomize G-CSF vs placebo at day 35
    ConsolidationHDMTX (2 g/m2) days 48 and 55 + MP (75 mg/m2/day) × 14 days
    • Pred indicates prednisone; VCR, vincristine; VP, etoposide; AraC, cytarabine; HDMTX, high-dose methotrexate; and MP, mercaptopurine.

  • Table 2.

    Systemic continuation therapy Total XIIIA and XIIIB

    WeekTotal XIIIA low riskTotal XIIIA intermediate/high riskTotal XIIIB low riskTotal XIIIB intermediate/high risk
    1MP + MTXVP + cycloMP + MTXVP + cyclo
    2MP + MTXMP + MTXMP + MTXMP + MTX
    3MP + MTXMTX + AraCMP + MTXMTX + AraC
    4Pred + VCRPred + VCR + asparaginaseDex + VCRDex + VCR
    5MP + MTXVP + cycloMP + MTXVP + cyclo
    6MP + MTXMP + HDMTXMP + MTXMP + HDMTX
    7MP + HDMTXVP + AraCMP + HDMTXVP + AraC
    8Pred + VCRPred + VCR + asparaginaseDex + VCRDex + VCR
    • Doses during continuation therapy were as follows: MP (mercaptopurine), 75 mg/m2/d; MTX (methotrexate), 40 mg/m2/wk; VP (etoposide), 300 mg/m2/wk; cyclo (cyclophosphamide), 300 mg/m2/wk; AraC (cytarabine), 300 mg/m2/wk; Pred (prednisone), 40 mg/m2/d; asparaginase (Elspar; Merck, West Point, PA), 10 000 IU/m2/wk; and dex (dexamethasone), 8 mg/m2/d. Patients at higher risk to develop central nervous system relapse received additional doses of intrathecal therapy along with cranial irradiation at 1800 cGy in 12 fractions over 2.5 weeks beginning at week 56; those with central nervous system leukemia at diagnosis received 2400 cGy in 16 fractions over 3 weeks beginning at week 56. Continuation therapy consisted of repeated 8-week cycles of the drugs listed above for a total of 120 weeks, except that (1) in both protocols, the HDMTX was replaced by MTX at 40 mg/m2 after week 55; (2) in the intermediate/high-risk arm of Total XIIIA, reinduction therapy was given at week 32–38, and asparaginase was omitted after reinduction; and (3) in both arms of Total XIIIB, reinduction therapy was given at weeks 16 to 21.

  • Table 3.

    Patient presenting features

    Age at diagnosis, yNo. (%)
     Younger than 115 (3.6)
     1 to 9259 (62.9)
     10 or older138 (33.5)
    Sex
     Male236 (57.3)
     Female176 (42.7)
    Race
     White311 (75.5)
     Black68 (16.5)
     Other33 (8.0)
    WBC count, cells/mm3
     Lower than 50 000302 (73.3)
     50 000 or higher110 (26.7)
    DNA index
     1.16 or higher92 (22.3)
     Other320 (77.7)
    CNS status
     CNS-2, 3 or traumatic with blasts166 (40.3)
     CNS-1, traumatic without blasts246 (59.7)
    Lineage
     B346 (84.0)
     T66 (16.0)
    Philadelphia chromosome
     Absent397 (96.4)
     Present13 (3.2)
     Not known2 (0.5)
    t(1;19)
     Absent386 (93.7)
     Present18 (4.4)
     Not known8 (1.9)
    t(4;11)
     Absent393 (95.4)
     Present11 (2.7)
     Not known8 (1.9)
    TEL/AML1
     Absent335 (81.3)
     Present60 (14.6)
     Not known17 (4.1)
    Received G-CSF
     Yes99 (24.0)
     No313 (76.0)
    Received irradiation
     Yes57 (13.8)
     No355 (86.2)
  • Table 4.

    Numbers of patients per protocol by irradiation and G-CSF therapy

    ProtocolNo G-CSFReceived G-CSF
    No
    irradiation
    Received
    irradiation
    No
    irradiation
    Received
    irradiation
    Total XIIIA low risk7040
    Total XIIIA intermediate/high risk62166313
    Total XIIIB low risk113040
    Total XIIIB intermediate/high risk8728141