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Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study

Yoav H. Messinger, Paul S. Gaynon, Richard Sposto, Jeannette van der Giessen, Elena Eckroth, Jemily Malvar and Bruce C. Bostrom for the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Consortium

Data supplements

Article Figures & Data

Figures

  • Figure 1

    Survival analysis of phase 2 patients. (A) OS of all 22 patients in phase 2 at 24 months is estimated to be 41% ± 13%. (B) Comparison of survival of patients who completed reinduction. Survival was significantly better in those who responded (CR or CRp) compared with those who did not (P < .001).

Tables

  • Table 1
  • Table 2

    Demographic and treatment data (n = 22)

    Sexn (%)
        Male14 (64)
        Female8 (36)
    Race/ethnicity
        White/non-Hispanic or unknown13 (59)
        White/Hispanic7 (32)
        Asian/non-Hispanic2 (9)
    Median age, y (range)12 (1.3-22.3)
    Lineage
        B-precursor ALL20 (91)
        T-cell ALL2 (9)
    Treatment attempts
        Failed 2 regimes17 (77)
        Failed 3 regimes5 (23)
    Previous BMT
        None18 (82)
        Yes4 (18)
    BM (at study entry) M322 (100)
    Treatment data
        Bortezomib: 4 planned doses22 (100)
        Completed therapy19 (86)
        Induction death3 (14)
        BM aplasiaNone
        Days to ANC > 750/μL, median (range)38 (27-48)
        Days to platelets > 75 000/μL, median (range)35 (27-41)
    • ALL indicates acute lymphoblastic leukemia; ANC, absolute neutrophil count; BMT, BM transplantation; and M3, > 25% BM blasts.

  • Table 3

    Response data

    TotalBT
    n22202
    CR14 (64)*14 (70)0
    CRp2 (9)2 (10)0
    OR (CR + CRp)16 (73)16 (80)0
    SD/PD2 (9)02 (100)
    Toxic deaths3 (14)3 (15)0
    Undetermined1 (4.5)1 (5)0
    BM response
        M117 (77)17 (85)0
        M2/M32 (9)02 (100)
        Toxic deaths3 (14)3 (15)0
    • Values are n (%).

    • B indicates B-precursor ALL; T, T-cell ALL; CR, complete remission; CRp, complete remission without platelet recovery; M1, < 5% bone marrow blasts; M2, 5%-25% BM blasts; M3, > 25% BM blasts; OR, overall response; PD, progressive disease; and SD, stable disease.

    • * 95% exact confidence interval 41%-83%.

    • 95% exact confidence interval 50%-89%.

    • Response could not be determined: M1 achieved but treated with additional chemotherapy before peripheral recovery.

  • Table 4

    Toxicity data

    CategoryToxicity gradeTotal
    345
    Hematologic1421022
    CardiacHypertension/hypotension3104
    CoagulationHypofibrinogenemia, coagulopathy, thrombosis, lower gastrointestinal hemorrhage5005
    GastrointestinalAnorexia, dehydration, diarrhea4004
    Pyrexia1001
    Infection45310
    MetabolicALT, AST, GGT, bilirubin6309
    Amylase, lipase1102
    Hypercalcemia, hypocalcemia7007
    Hypophosphatemia3003
    Hyperglycemia, hypoglycemia6107
    Hyperkalemia, hypokalemia4408
    Hypernatremia0101
    Hyponatremia8008
    Hypoalbuminemia5005
    Total metabolic176018
    NeurologicCerebral ischemia, encephalopathy1012
    Peripheral neuropathy: motor and sensory2002
    PainAbdominal, extremity, external ear3003
    RespiratoryCough, hiccups, hypoxia, pleural effusion, pneumonitis3205
    Total patients with toxicity2121322
    • ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; and GGT, gamma glutamyl transpeptidase.