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Related and unrelated donor transplantation for β-thalassemia major: results of an international survey

Chunfu Li, Vikram Mathews, Soyoung Kim, Biju George, Kyle Hebert, Hua Jiang, Changgang Li, Yiping Zhu, Daniel A. Keesler, Jaap Jan Boelens, Christopher C. Dvorak, Rajni Agarwal, Jeffery J. Auletta, Rakesh K. Goyal, Rabi Hanna, Kimberly Kasow, Shalini Shenoy, Angela R. Smith, Mark C. Walters and Mary Eapen

Article Figures & Data

Figures

  • Figure 1.

    Event-free survival. (A) Event-free survival by age at transplantation. The 5-year probabilities of event-free survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years were 86% (83% to 89%), 80% (76% to 84%), and 63% (48% to 78%), respectively. (B) Event-free survival by donor type. The 5-year probabilities of event-free survival after HLA-matched relative, HLA-mismatched relative, HLA-matched unrelated, and HLA-mismatched unrelated donor transplants were 86% (83% to 88%), 70% (61% to 79%), 82% (75% to 89%), and 78% (70% to 86%), respectively.

  • Figure 2.

    Overall survival. (A) Overall survival by age at transplantation The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years were 90% (88% to 93%), 84% (80% to 87%), and 63% (45% to 82%), respectively. (B) Overall survival by donor type. The 5-year probabilities of overall survival after HLA-matched relative, HLA-mismatched relative, HLA-matched unrelated, and HLA-mismatched unrelated donor transplants were 89% (87% to 91%), 73% (64% to 82%), 87% (81% to 93%), and 83% (74% to 91%), respectively.

  • Figure 3.

    Graft failure. (A) Graft failure by age at transplantation. The 5-year probabilities of graft failure for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years were 8% (6% to 10%), 10% (7% to 12%), and 22% (7% to 34%), respectively. (B) Graft failure by donor type. The 5-year probabilities of graft failure after HLA-matched relative, HLA-mismatched relative, HLA-matched unrelated, and HLA-mismatched unrelated donor transplants were 9% (6% to 11%), 21% (12% to 29%), 6% (3% to 9%), and 11% (5% to 18%), respectively.

Tables

  • Table 1.

    Patient and transplant characteristics

    No. (%)
    Age at transplantation, y
     ≤6638 (57)
     7-15439 (40)
     16-2533 (3)
    Sex
     Male/female696 (63)/414 (37)
    Red blood cell transfusions prior to transplantation
     <2040 (4)
     20-50304 (27)
     >50634 (57)
     Not reported132 (12)
    Iron chelation
     Adequate117 (11)
     Inadequate981 (88)
     Not reported12 (1)
    Hepatomegaly
     Absent280 (25)
     Present806 (73)
     Not reported24 (2)
    Donor type
     HLA-matched relative677 (61)
     HLA-mismatched relative78 (7)
     HLA-matched unrelated252 (23)
     HLA-mismatched unrelated103 (9)
    Graft type
     Bone marrow321 (29)
     Peripheral blood682 (61)
     Cord blood107 (10)
    In vivo T-cell depletion
     Yes/none827 (75)/283 (25)
    Conditioning regimen
     BU/Cy/TT/FLU376 (34)
     BU/Cy/FLU259 (23)
     BU/Cy249 (22)
     Treosulfan/TT/FLU169 (15)
     BU or melphalan ± TT ± FLU57 (5)
    GVHD prophylaxis
     Calcineurin inhibitor/methotrexate/mycophenolate187 (17)
     Calcineurin inhibitor/methotrexate446 (40)
     Calcineurin inhibitor/mycophenolate350 (32)
     Calcineurin inhibitor alone31 (3)
     Posttransplant Cy/cyclosporine/mycophenolate96 (9)
  • Table 2.

    Risks factors for event-free survival and overall survival

    OutcomesEvents/evaluableHR (95% CI)P
    Event-free survival
     Age at transplantation, y
      ≤684/6381.00<.001
      7-1587/4391.46 (1.07-2.00).017
      16-2514/333.03 (1.68-5.47)<.001
    Donor type
      HLA-matched relative108/6771.00<.001
      HLA-mismatched relative29/782.75 (1.81-4.16)<.001
      HLA-matched unrelated26/2521.25 (0.75-2.07).39
      HLA-mismatched unrelated22/1031.60 (0.95-2.71).08
     Conditioning regimen
      Bu/Cy/TT/FLU28/3761.00<.001
      Bu/Cy/FLU27/2591.32 (0.78-2.25).31
      Bu/Cy71/2493.11 (1.80-5.40)<.001
      Treosulfan/TT/FLU38/1692.79 (1.61-4.83)<.001
      Bu or melphalan ± TT ± FLU21/575.09 (2.81-9.21)<.001
     Transplant period
      2012-201674/6571.00.008
      2006-201173/3391.66 (1.17-2.35).01
      2000-200538/1141.96 (1.16-3.33).01
    Overall survival
    Age at transplantation, y
      ≤657/6381.00<.001
      7-1573/4391.84 (1.29-2.63)<.001
      16-2512/334.35 (2.28-8.30)<.001
    Donor type
      HLA-matched relative83/6771.00<.001
      HLA-mismatched relative25/783.30 (1.93-4.77)<.001
      HLA-matched unrelated19/2521.13 (0.64-2.02).67
      HLA-mismatched unrelated15/1031.56 (0.85-2.88).16
    Conditioning regimen
      Bu/Cy/TT/FLU25/3761.00<.001
      Bu/Cy/FLU22/2591.32 (0.74-2.34).34
      Bu/Cy55/2493.61 (2.15-6.07)<.001
      Treosulfan/TT/FLU30/1692.22 (1.23-4.030.008
      Bu or melphalan ± TT ± FLU10/572.55 (1.18-5.50).02
  • Table 3.

    Five-year probabilities of event-free and overall survival by age and donor type

    Donor typeEvent-free survival (95% CI), %Overall survival (95% CI), %
    Age, ≤6 y
     HLA-matched relative88 (84-91)92 (89-95)
     HLA-mismatched relative73 (59-86)75 (61-87)
     HLA-matched unrelated89 (83-93)93 (88-96)
     HLA-mismatched unrelated83 (73-91)89 (81-96)
    Age, 7-15 y
     HLA-matched relative80 (75-85)84 (79-88)
     HLA-mismatched relative56 (39-73)62 (44-78)
     HLA-matched unrelated89 (82-95)91 (83-97)
     HLA-mismatched unrelated71 (54-85)79 (63-91)
    • Patients aged 16-25 years: N = 24 patients who received HLA-matched related donor transplantation with event-free survival of 58% (14 of 24) and overall survival of 63% (15 of 24). N = 4 patients received HLA-mismatched related donor transplantation and only 2 patients are alive. N = 4 patients received HLA-matched unrelated donor transplantation and all patients are alive. N = 1 patient received HLA-mismatched unrelated donor transplantation and is death.

  • Table 4.

    Risks factors for graft failure, grade II-IV acute and chronic GVHD

    OutcomesEvents/evaluableHR (95% CI)P
    Graft failure
     Age at transplantation, y
      ≤649/6381.00.02
      7-1543/4391.30 (0.86-1.96).21
      16-257/333.03 (1.36-6.73).006
     Donor type
      HLA-matched relative58/6771.00<.001
      HLA-mismatched relative17/782.84 (1.65-4.88)<.001
      HLA-matched unrelated13/2520.61 (0.33-1.11).10
      HLA-mismatched unrelated11/1031.31 (0.68-2.50).42
    Acute GVHD
    Age at transplantation, y
      ≤693/6341.00.002
      7-1578/4361.10 (0.71-1.70).66
      16-2510/332.23 (1.30-3.84).003
     Donor type
      HLA-matched relative80/6741.00<.001
      HLA-mismatched relative27/773.33 (2.15-5.17)<.001
      HLA-matched unrelated54/2512.44 (1.72-3.46)<.001
      HLA-mismatched unrelated20/1011.94 (1.19-3.16).008
     Transplant period
      2012-201685/6531.00<.001
      2006-201168/3381.70 (1.23-2.35).001
      2000-200528/1122.50 (1.61-4.00)<.001
    Chronic GVHD
     Donor type
      HLA-matched relative52/6271.00<.001
      HLA-mismatched relative14/702.64 (1.42-4.89).002
      HLA-matched unrelated21/2492.13 (1.13-4.00).02
      HLA-mismatched unrelated24/1014.25 (2.43-7.44)<.001
     Conditioning regimen
      Bu/Cy/TT/FLU17/3721.00<.001
      Bu/Cy/FLU24/2552.03 (1.09-3.78).03
      Bu/Cy41/2236.78 (3.59-12.81)<.001
      Treosulfan/TT/FLU20/1407.25 (3.41-15.41)<.001
      Bu or melphalan ± TT ± FLU9/571.94 (0.82-4.60).13
     Recipient sex
      Male82/6591.00
      Female29/3880.59 (0.38-0.91).02