Table 5.1.
Umbilical cord blood transplantation for patients with sickle cell disease
| Refs. | Transplant regimen | TNC dose median (range) × 107/kg | HLA match | No. of patients (age) | Alive without SCD | Acute GvHD (Gr 2–4) | Chronic GvHD (extensive) | Death (cause) |
|---|---|---|---|---|---|---|---|---|
| Related cord blood donors | ||||||||
| Brichard et al. [33] | Bu 16 mg/kg, Cy 200 mg/kg, ATG, CSA | 4.6 | 6/6 | 1(5) | 1 | 0 | 0 | 0 |
| Miniero et al. [71] | Bu 16 mg/kg, Cy 200 mg/kg, CSA ± MTX | (3.5–6.0) | 6/6 | 3(3–11) | 2 | 0 | 0 | 0 |
| Gore et al. [72] | Bu 726 mg/m2, Cy 200 mg/kg, ATG, CSA | 2.3 | 6/6 | 1(9) | 1 | 0 | 0 | 0 |
| Walterset al. [44] | NR | NR | 6/6 42 pts, 4/6 4 ptsa |
8(NR) | 6 | NR | NR | 1(intractable seizures) |
| Matthes- Martin et al. [73] | TLI(2 Gy), Flu 160 mg/m2, Mel 140 mg/m2, Alem 1 mg/kg, CSA, MMF | NR | 6/6 | 1(11.1) | 1 | 0 | 0 | 0 |
| Locatelli et al. [34] | Bu ± Flu ± Cy ± ATG/ALG ± TT, CSA ± MTX | 3.9(1.5—14)b | 6/6 | 30(2–20)b | 27 | 11%(Gr 2–3)b | 0 | 3(2 hemorrhage, 1 organ failure)b |
| Total | - | - | Mostly 6/6 | 44 | 38(86%) | 11% | 0 | 9%(of total) |
| Unrelated cord blood donors | ||||||||
| Mazur et al. [74] | Rituximab, Alem, TT (600 mg/m2), 600 cGy TBI, tac + MMF3 | 4.2 | 4/6 | 1(9) | 1 | 0 | 0 | 0 |
| Adamkie- wicz et al. [75] |
Mixed, 4 pts myeloablative, 3 pts reduced-intensity | (1.5–9.3) | 5/6 2 pts, 4/6 5 pts | 7(3.4–16.8) | 3 | 4 | 1 | 1(multi-organ failure) |
| Sauter et al. [76] | Reduced-intensity | 3.8 and 2.0c | 5/6 | 1(22) | 1 | 0 | 0 | 0 |
| Ruggeri et al. [36] | Mixed, 9 pts myeloablative, 7 pts reduced-intensity | 6(2–12) | 6/6(2) | 16(6) | 8 | 23%d | 16%d | 1 acute GvHD |
| 5/6(4) | ||||||||
| 4/6(10) | ||||||||
| Kamani et al. [37] | Alem 48 mg, Flu 150 mg/m2, Mel 140 mg/m2, CSA or tac + MMF | 6.4(3.1–7.6) | 6/6(1) | 8(7.4–16.2) | 3 | 2(Gr 2) | 1(extensive) | 1(respiratory failure) |
| 5/6(7) | ||||||||
| Radha- krishnan et al. [77] | Bu 12.8–16 mg/kg, Flu 180 mg/m2, Alem 54 mg/m2, MMF, tac | NR | NR | 8(1–10) | 4 | 4 | 1(limited) | 3(infection) |
| Total | - | - | Mostly mismatched | 41 | 20(49%) | 20%(of total) | 7%(of total) | 15%(of total) |
| 40%(of engrafted) | 15%(of engrated) | |||||||
Abbreviations: TNC total nucleated cell, SCD sickle cell disease, GvHD graft-versus-host disease, Bu busulfan, Cy cyclophosphamide, ATG anti-thymocyte globulin, CSA cyclosporine A, N/A not applicable, MTX methotrexate, Gr grade, NR not reported, pts patients, TLI total lymphoid irradiation, Gy gray, Flu fludarabine, Mel melphalan, Alem alemtuzumab, MMF mycophenolate mofetil, ALG anti-lymphocyte globulin, TT thiotepa, TBI total body irradiation, tac tacrolimus
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
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
Patient received a double umbilical cord unit transplant
Includes 51 patients: 35 have TM and 16 have SCD