A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Dolores Grosso, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L. Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss and Neal Flomenberg

Article Figures & Data


  • Figure 1

    Fever curves after DLI are correlated with clinical events. A typical temperature curve from an engrafting patient is shown in green. Curves from the 2 patients with anti-donor antibodies who rejected their grafts are shown in red and blue. The boundary between the febrile and afebrile ranges (100.4°F) is shown by the horizontal solid black line. The afebrile range is shaded gray. Engrafting patients generally developed fever within 24 hours after DLI. The fever spikes persisted despite the use of acetaminophen and other comfort measures until after the second dose of CY. In the setting of anti-donor antibodies, patients developed fever within a few hours of the DLI, rapidly defervesced, and remained afebrile thereafter.

  • Figure 2

    Neutrophil and platelet engraftment. Cumulative incidences of neutrophil and platelet engraftment were 85.2% and 74.1%, respectively.

  • Figure 3

    Immune recovery after haploidentical transplantation. CD3+/CD4+ cell counts (A) and CD3+/CD8+ cell counts (B) of 16 patients alive and disease-free at least 6 months after HSCT are shown.

  • Figure 4

    Acute GVHD. Cumulative incidences of grades II-IV and III-IV GVHD were 59.2% and 7.4%, respectively.

  • Figure 5

    Relapse-related mortality and NRM. Cumulative incidences of relapse-related mortality and NRM were 29.6% and 22.2%, respectively.

  • Figure 6

    Probability of overall survival. Survival for all patients in the trial is shown as the solid black line (48% 3-year overall survival). Patients without BM morphologic or radiographic evidence of disease at the time of transplantation are shown with the dashed line (75% 3-year overall survival). Patients with BM or radiographic evidence of disease are shown in the dotted line (27% 3-year overall survival).


  • Table 1

    Patient characteristics

    Subjects, n27
    Median age, y (range)
        Recipient52 (19-67)
        Donor39 (24-65)
    Disease and disease status at HSCT
        AML CR1 with high-risk features*5
        AML CR22
        AML primary induction failure2
        AML in resistant relapse7
        Biphenotypic leukemia with disease at HSCT1
        ALL CR2 (Ph)3
        ALL (Ph+) morphologic remission1
        NHL chemotherapy resistant3
        Aplastic anemia1
        Previous transplant2
        Secondary malignancy2
    Recipient/donor transplantation combinations
    CMV serostatus recipient (R) and donor (D)
    HLA antigen mismatches (GVH direction) (A, B, Cw, DRB1), n
    KIR mismatches
        HLA-C group 15
        HLA-C group 24
        HLA-C and HLA-Bw42
        No KIR mismatch15
    • * Based on cytogenetics, secondary disease, CNS/tissue involvement, or arising from MDS.

    • Patient had 4 mismatches in HVG direction only and was counted for toxicity only

    • KIR ligand missing in recipient but present in donor. Missing self as defined by Ruggeri et al.18

    • AML indicates acute myeloid leukemia; CR, complete remission; Ph, Philadelphia chromosome; ALL, acute lymphoblastic leukemia; MDS, myelodysplastic syndrome; and NHL, nonHodgkin lymphoma.

  • Table 2

    Graft characteristics

    Step 1Step 2
    CD3+/kg × 108 median (range)CD34+/kg × 106 median (range)Residual CD3+ cells/kg in CD34+ product × 104 median (range)
    2.0 (1.7 in 1 patient, 2.0 in 26 patients)3.6 (1.3-7.4)0.51 (0.13-6.9)