Table 5.2.
Umbilical cord blood transplantation for patients with thalassemia major
| Refs. | Transplant regimen | HLA match | TNC dose median (range) × 107/kg | Pesaro Class | No. of patients (age) | Alive without TM | Acute GvHD (Gr 2–4) | Chronic GvHD | Death (cause) |
|---|---|---|---|---|---|---|---|---|---|
| Related cord blood donors | |||||||||
| Issaragrisil et al. [38] | Bu 14 mg/kg, Cy 200 mg/kg, CSA, MTX | 6/6 | 3.9 | NR | 1(2.5) | 1 | 0 | 0 | 0 |
| Chik et al. [78] | Bu 16 mg/kg, Cy 150 mg/kg, ATG 110 mg/kg | 6/6 | 2.9 | NR | 1(10) | 0 | 0 | 0 | 0 |
| Lau et al. [79] | Bu 20 mg/kg, Cy 200 mg/kg, ATG 90 mg/kg, CSA, MTX | 6/6 | 8.8(6.2–11.4) | NR | 2(2.2–3.8) | 2 | 2(Gr 3) | 0 | 0 |
| Chan & Lin [80] | Bu 22 mg/kg, Cy 200 mg/kg | 6/6 | NR | NR | 1(2.1) | 1 | 0 | 0 | 0 |
| Hongeng et al. [81] | Bu 20 mg/kg, Cy 200 mg/kg, ATG 40 mg/kg, methylpred, CSA | 4/6 | 6.1 | NR | 1(3) | 0 | 1(Gr 2) | 0 | 1(sepsis) |
| Zhou et al. [82] | Bu 20 mg/kg, Cy 200 mg/kg, ATG 90 mg/kg, CSA, MTX | Class 1 | 4.8a | 5/6 | 1(L7) | 1 | 1 | 0 | 0 |
| Fang et al. [49] | Mixed | 6/6(6) | 6.6(3.4–12.7) | Class 2, 6 | 9(3.5–10) | 4 | 2 | 1 | 1(GvHD) |
| 5/6(1) | Class 3, 3 | ||||||||
| 3/6(2) | |||||||||
| Vanichsetakul et al. [83] | Bu 16–20 mg/kg, Cy 200 mg/kg, ATG, CSA ± methylpred | 6/6(3) | 2.9(1.49–5.3) | Class 1, 1 | 5(2.1–15) | 3(60%)b | 1 | 0 | 1 (Sepsis) |
| 4/6(1) | Class 2, 1 | ||||||||
| Class 3, 3 | |||||||||
| Walters et al. [44] | NR | NR | NR | 6/6 42 pts, 4/6 4 ptsc | 14(NR) | 12 | NR | NR | NR |
| Sun et al. [84] | Bu, Cy, ATGd, CSA ± MMF | 6/6(8) | (3.63–16.0) | Class 1 or 2, 10 | 12e (1.3–8.3) | 7 | 4 | 0 | 1(infection) |
| 4/6(4) | Class 3,2 | ||||||||
| Sun et al. [39] | Bu, Cy, ATGd | 6/6 | 20.8(19.5–23.3) | Class 2, 1 | 3 | 3f | 0 | NR | 0 |
| Class 3, 2 | |||||||||
| Goussetis et al. [45] | Bu 16 mg/kg, Cy 200 mg/kg, ATG 40 mg/kg ± Flu, CSA | 6/6(7) | 2.5(0.3–8) | Class 1, 1 | 8(3–15) | 7g | NR | NR | 0 |
| 5/6(1) | Class 2, 2 | ||||||||
| Class 3, 5 | |||||||||
| Locatelli et al. [34] | Bu ± Flu ± Cy ± ATG/ALG ± TT, CSA ± MTX | 6/6 | 3.9(1.5—14)h | Class 1 40 | 66(2–20)h | 53 | 7h | 0 | 3(2 hemorrhage, 1 organ failure)h |
| Class 2, 23 | |||||||||
| Class 3, 2 | |||||||||
| Total | - | Mostly 6/6 | - | - | 124 | 94(76%) | 15%(of total) | 1% | 6%(of total) |
| 19%(of engrafted) | |||||||||
| Unrelated cord blood donors | |||||||||
| Fang et al. [85] | Bu 20 mg/kg, Cy 200 mg/kg, Flu 150 mg/m2, TT 6 mg/kg, ATG 90 mg/kg, tac, MTX, methylpred | 6/6 | 7.5 | Class 3 | 1(5) | 1 | 1(Gr 3) | 0 | 0 |
| Tan et al. [86] | Bu 18 mg/kg, Cy 120 mg/kg, ATG, CSA, MTX | 4/6 | 6 | Class 2 | 1(5.5) | 1 | 0 | 0 | 0 |
| Hall et al. [87] | Bu 320 mg/m2, Cy 200 mg/kg, ATG 90 mg/kg, CSA, Methylpred | 4/6 | 19.1 | NR | 1(0.17) | 1 | 0 | 0 | 0 |
| Bradley et al. [88] | Bu, Flu, ATG, tac, MMF | 5/6 | 9.5 | NR | 1(0.5) | 0 | 0 | 0 | 0 |
| Ruggeri et al. [36] | Mixed, 30 pts myeloablative, 5 pts reduced-intensity | 6/6(5) | 4.9(1.1–9) | Class 1,9 | 35(4) | 8 | 23%i | 16%i | 12(7 transplant- related complications, 5 primary graft failure) |
| 5/6(14) | Class 2, 2 | ||||||||
| 4/6(15) | Class 3,4 | ||||||||
| NR 20 | |||||||||
| Jaing et al. [40] | Bu 14 mg/kg, Cy 200 mg/kg, ATG, CSA, methylpred | 6/6(8) | 7.8(2.8–14.7) | NR | 35(1.2–14) | 28j | 28 | 1 | 4(3 hemorrhage), 1 septicemia) |
| 5/6(16) | |||||||||
| 4/6(27) | |||||||||
| Gumuscu et al.k [89] | Bu 12.8 mg/kg, Cy 200 mg/kg, ATG 120 mg/kg, tac, MMF | 5/6 | 4.9 | N/A | 1(3.7) | 1 | 1 | 0 | 0 |
| Total | - | Mostly mismatched | - | - | 75 | 40(53%) | 51%(of total) | 9%(of total) | 21% |
| 95%(of engrafted) | 18%(of engrafted0 | ||||||||
Abbreviations: TNC total nucleated cell, TM thalassemia major, GvHD graft-versus-host disease, Bu busulfan, Cy cyclophosphamide, CSA cyclosporine A, MTX methotrexate, NR not reported, N/A not applicable, ATG anti-thymocyte globulin, Gr grade, methylpred methylprednisolone, MMF mycophenolate mofetil, Flu fludarabine, ALG anti-lymphocyte globulin, TT thiotepa, tac tacrolimus, pts patients
Patient has hemoglobin Bart’s disease. TNC is total count, not per kg
One additional patient maintained mixed chimerism but remains anemi
Includes 47 patients in the entire cohort: 14 patients with thalassemia, 8 patients with SCD, 25 other. Ten patients received peripheral blood stem cells or bone marrow from the same sibling donor
HLA-mismatched patients received hypertransfusions, continuous intravenous desferrioxamine, Hydroxyurea, Flu, Bu, Cy, and ATG
One donor was not a sibling
All patients received accompanying bone marrow from the same sibling donor
Two patients were re-transplanted and five patients received accompanying bone marrow from the same sibling donor
Includes subjects with SCD and thalassemia. GvHD percentage estimated with the assumption that GvHD incidence was the same in both populations since incidence not differentiated in patients with SCD versus thalassemia. Hemoglobin disorder type was also not differentiated among patients who died
Includes 51 patients: 35 have TM and 16 have SCD
Includes six patients who required second transplants (five CB, one peripheral blood stem cell)
Patient had homozygous α-thalassemia disease