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Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

Koen van Besien, Andrew Artz, Richard E. Champlin, Danielle Guarneri, Michael R. Bishop, Julianne Chen, Usama Gergis, Tsiporah Shore, Hongtao Liu, Gabriela Rondon, Sebastian A. Mayer, Samer A. Srour, Wendy Stock and Stefan O. Ciurea

Article Figures & Data

Figures

Tables

  • Table 1.

    Patient, disease, and transplant characteristics

    Patient characteristicsHaplo, n (%)Haplo-cord, n (%)P
    N170137
    Age, median (IQR 25-75)41 (25-51)44 (45-53).006
    Female/male74/9659/78
    Transplant indication
     AML81 (48)63 (46).01
     MDS10 (6)19 (14)
     ALL34 (20)16 (12)
     NHL/HL16 (10)24 (18)
     CML23 (14)8 (6)
     Other5 (3)*7 (5)
    Disease risk index
     Low21 (12)9 (7).02
     Intermediate75 (44)62 (45)
     High66 (39)44 (32)
     Very high8 (5)22 (16)
    Comorbidity
     HCT CI <353 (31)50 (36).7
     HCT CI ≥3116 (69)86 (64)
    ABO
     No mismatch126 (74)46 (34)<.000
     Major mismatch5 (3)35 (26)
     Minor mismatch37 (22)38 (28)
     Major and minor mismatch2 (1)18 (13)
    CMV§
     Rec neg/donor neg9 (5)14 (10).01
     Rec neg/donor Pos10 (6)20 (15)
     Rec pos148 (87)102 (74)
     Missing31
    Sex||
     Sex match98 (58)72 (53).38
     Sex mismatch72 (42)64 (46)
     Missing1
    Conditioning
     Fludarabine melphalan alone43 (25)112 (82)
     Fludarabine melphalan + TBI26 (15)25 (18)#
     Fludarabine melphalan + thiotepa101 (59)
    Haploidentical donor source
     Peripheral blood11 (7)137 (100)
     Bone marrow159 (93)0
    MFU survivors, mo41540.0001
    • ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia, CML, chronic myeloid leukemia, HCT CI, hematopoietic cell transplantation comorbidity index; IQR, interquartile range; MDS, myelodysplastic syndromes; NHL/HL, non-Hodgkin lymphoma/Hodgkin lymphoma; MFU, median follow-up.

    • * 4 chronic lymphocytic leukemia, 1 multiple myeloma.

    • 1 multiple myeloma, 3 chronic lymphocytic leukemia, 3 myeloproliferative disorder.

    • For haplo-cord, only CBU blood group is considered.

    • § For haplo-cord, seropositivity of either CBU or haplo donor is considered positive.

    • || For haplo-cord, only CBU sex is considered.

    • TBI 200 cGy.

    • # 22 TBI 400 cGy 3 TBI 600 cGy.

  • Table 2.

    Engraftment and GVHD

    EventP
    Median days to ANC >0.5 × 109/L (IQR)
     Haplo18 (16-20).001
     Haplo-cord11 (10-14)
    Median days to platelet >20 × 109/L (IQR)
     Haplo25 (20-32).025
     Haplo-cord22 (17-36)
    Cumulative incidence grade 2-4 acute GVHD, day 100 (95% CI)
     Haplo33% (27-39).0001
     Haplo-cord16% (9-23)
    Cumulative incidence grade 3-4 acute GVHD, day 100 (95% CI)
     Haplo9% (5-13).275
     Haplo-cord5% (1-9)
    Cumulative incidence chronic GVHD at 1 y (95% CI)
     Haplo16% (12-20).0001
     Haplo-cord4% (0-10)
    • ANC, absolute neutrophil count.

  • Table 3.

    Relapse, NRM, PFS, and OS (multivariate analysis)

    P
    EventnHR (95% CI)OverallPairwise*
    NRM
     Study cohort.36
      Haplo1701.0
      Haplo-cord1371.34 (0.83-2.16)
     CIBMTR disease risk index.0006
      Low300.9 (0.4-2.2).80
      Intermediate1371
      High1102.00 (1.21-3.31).007
      Very high371.44 (0.94-2.18).09
    Age, y.01
      ≥401861
      <401210.51 (0.30-0.84)
    Relapse/progression
    Study cohort.6
      Haplo1701
      Haplo-cord1370.48 (0.31-0.75)
     CIBMTR disease risk index<.0001
      Low300.5 (0.2-1.4).19
      Intermediate1371
      High1102.35 (1.51-3.68).0002
      Very high372.22 (1.66-2.97)<.0001
    Conditioning.004
      No TBI2531
      TBI540.37 (0.19-0.74)
    Disease-free survival
    Study cohort.5
      Haplo1701
      Haplo-cord1370.91 (0.67-1.22)
    CIBMTR disease risk index<.0001
      Low300.7 (0.35-1.4).28
      Intermediate1371
      High1102.19 (1.57-3.06)<.0001
      Very high301.88 (1.49-2.39)<.0001
    Conditioning.02
      No TBI2531
      TBI540.61 (0.39-0.94)
    Age, y
      ≥401861.06
      <401210.75 (0.55-1.02)
    OS
    Study cohort0.21
      Haplo1701
      Haplo-cord1370.81 (0.62-1.18)
    CIBMTR-disease risk index<.0001
      Low300.8 (0.4-1.5).51
      Intermediate1371
      High1102.14 (1.50-3.05)<.0001
      Very high371.73 (1.35-2.21)<.0001
    Age, y
      ≥401861.08
      <401210.74 (0.54-1.04)
    • Risk factors evaluated: age (<40 vs ≥40), sex, disease (AML/MDS vs lymphoma vs ALL vs other, HCT CI < 3 vs ≥3, CIBMTR DRI, use of TBI).

    • * Reference group: intermediate.

  • Table 4.

    Nonrelapse deaths

    Haplo (n = 170)Haplo-cord (n = 137)
    n (%)Cumulative Incidence at 1 y, % (95% CI)n (%)Cumulative incidence at 1 y, % (95% CI)P (Gray test)
    Fatal infection13 (7)7.6 (7.4-8)20 (15)6.6 (6.2-7.0).51
    GVHD9 (5)3.5 (3.2-3.8)1 (1)0.0 (0-0.01).02
     Acute GVHD7 (4)2.3 (2.1-2.5)1 (1)0.0 (0-0.01).06
     Chronic GVHD2 (1)1 (0.8-1.2)00.20
    PTLD004 (3)2.9 (2.6-3.2).01
    Graft rejection/poor graft function3 (1.5)1.8 (1.6-2)8 (6)5 (4.6-5.4).06
    Unknown5 (3)0
    Other9 (5)*5 (3.5)
    • * Haplo: hemorrhage, 3; secondary malignancy, 1; liver failure/veno-occlusive disease, 1; adult respiratory distress syndrome/respiratory failure, 2; cardiac failure, 2.

    • Haplo-cord: liver failure/VOD, 1; ARDS/respiratory failure, 3; vasculitis, 1.