Studies of unrelated umbilical cord blood (UCB) transplantation in adults.
| . | Laughlin et al7 . | Sanz et al8 . | Rocha et al7,9 (Eurocord) . | Goldberg et al10 . | Cornetta et al11 (COBLT) . | Ooi et al12 . | Ooi et al13 . | Long et al14 . |
|---|---|---|---|---|---|---|---|---|
| a EFS is better in patients receiving graft with CD34+ cells >1.2 × 105/kg. | ||||||||
| b Patients under the age of 30 had significantly better survival. | ||||||||
| c100 day TRM is lower in patients with disease in chronic phase or remission, N.C.dose infused ≥ 2.0 × 107/kg and transplant performed after January 1998. | ||||||||
| d 10 patients received ex vivo expanded UCBT. | ||||||||
| e The high mortality and relapse reflects the poor risk patients enrolled. | ||||||||
| f All de novo AML. | ||||||||
| g All except 1 patients received UCB transplant as an upfront treatment and all patients received > 2 × 107 N.C. per weight, perhaps due to smaller size of patients (median weight 51 kg). | ||||||||
| h CD34+ cell dose infused correlated with rate of platelet recovery and age > 31 years was significant predictor of poorer event-free survival. | ||||||||
| *19 of the 57 patients were included in the study published by Laughlin et al.7 | ||||||||
| ** platelet > 50,000/μL | ||||||||
| *** All had MDS-related secondary acute myeloid leukemia | ||||||||
| **** 9 of 12 evaluable patients had acute acute graft-versus-host disease. | ||||||||
| Abbreviations: NA, not available; TRM, therapy-related mortality; N.C., nucleated cell dose; TAI , thoraco-abdominal radiation; Ara-C, cytarabine arabinoside; TBI, total body irradiation; ATG, antithymocyte globulin; Bu, bulsulfan; Cy, cyclophosphamide; Thio, thiotepa; Flu, fludarabine; Mel, melphalan; Pred, prednisone; CSA, MTX, methotrexate; GVHD, graft-versus-host disease; MDS, myelodysplastic syndrome | ||||||||
| Number of patients | 68 | 22 | 108 | 19 | 34 | 18 | 13 | 57* |
| Median Age (range, years) | 31.4 (17.6–58.1) | 29 (18–46) | 26 (15–53) | 48 (20–59) | 34.5 (18.2–55) | 43 (21–52) | 40 (20–51) | 31 (18–58) |
| Median weight (range, kg) | 69.2 (40.9–115.5) | 70 (41–85) | 60 (35–110) | 69 (52–126) | NA | 55.2 (NA) | 51 (43–68) | 70 (46–110) |
| Diseases (n) | ||||||||
| Hematological malignancies | 54 | 21 | 96 | 18 | 32 | 18 | 13 | 50 |
| Bone marrow failure syndrome/MDS | 13 | 1 | 12 | 1 | 2 | 6 | ||
| Number of HLA loci disparity (n) | ||||||||
| 0 | 2 | 1 | 6 | 4 | 1 | 0 | 0 | 2 |
| 0 | 2 | 1 | 6 | 4 | 1 | 0 | 0 | 2 |
| 1 | 18 | 13 | 38 | 8 | 10 | 4 | 4 | 8 |
| ≥ 2 | 48 | 8 | 64 | 7 | 23 | 14 | 9 | 47 |
| Preparative regimen (n) | TBI-based/ATG (n = 51) Bu-based/ATG (n = 14) Others/ATG (n = 4) | Thio/Bu/Cy/ATG (n = 21) Thio/Flu/ATG (n = 1) | NA | Cy/TBI/ATG (n = 13) Mel/TBI/ATG (n = 4) Bu/Cy (n = 2) | Cy/TBI (n = 27) Bu/Mel (n = 7) | TBI/Ara-C/Cy (n = 17) TBI/Ara-C/Flu (n = 1) | Cy/TBI/Ara-C (n = 13) | Cy or Mel with TBI or BU/ ATG n = 41 TAI/Cy/ATG (n = 1) |
| GVHD prophylaxis | CSA/Pred (n = NA) CSA (n = NA) | CSA/Pred (n = 22) | CSA/Pred (n = 77) Others (n = 31) | CSA/Pred (n = 13) FK506/Pred (n = 6) | NA CSA/MTX (n = 16) | CSA (n = 2) | CSA/MTX (n = 13) | CSA (n = 1) CSA/Pred (n = 56) |
| Median time to engraftment (range, days) | ||||||||
| ANC > 500/μL | 27 (13–59) | 22 (13–52) | 32 (13–60) | 28 (NA) | 28.5 (13–55) | 23 (16–41) | 22.5 (19–35) | 26 (12–55) |
| Platelet > 20,000/μL | 58 (35–142) | 69 (49–153) | 129 (26–176) | 56 (NA) | NA | 49 (31–263)** | 49 (30–164)** | 84 (35–167) |
| Probability of myeloid engraftment | 90% by 42 days | 100% at 60 days | 81% by day 60 | 75% by day 60 | 72% at day 60 | 94% | 92% | 80% at day 50 |
| GVHD (n) ( probability, %) | ||||||||
| Acute Grade II–IV | 33 (60%) | 16 (NA) | 44 (38) | NA | 11 (38%) | 10 (55%) | 9**** | 17 (41%) |
| Acute Grade III–IV | 11 (20%) | 7 (NA) | 27 (NA) | NA | 6 (21%) | 1 (6%) | – | 9 (22%) |
| Chronic/patients at risk | 12/33 | 9/10 | 15/58 | NA | NA | 14/18 | 8/11 | 8/25 |
| Median cell dose (range) | ||||||||
| N.C. infused (× 107/kg) | 1.6 (0.6–4) | 1.71 (1.01–4.96) | 1.71(0.2–6) | 1.8 (0.4–5.3) | 1.73 (1.11–3.75) | 2.51 (1.16–5.29) | 2.43 (2.09–4.06) | 1.5 (0.54–2.78) |
| CD34+cells infused (× 105/kg) | 1.2 (0.2–16.7) | 0.79 (0.27–2.60) | NA | NA | NA | NA | NA | 1.37 (0.02–12.45) |
| Therapy-related mortality (%) | 50% at 100 day | 43% at 100 day | 54% at 100 day | NA | NA | 6% | 0% | 56% |
| Survival (%) | NA | NA | 27% at 1 year | 20% for good risk and 21% for poor risk at 1 year | 30% at 180 days | 76% at 2 years | 76.2% at 2 years | 19% at 3 years |
| Event-free survival (%) | 26% at 40 monthsa | 53% at 1yearb | 21% at 1 yearc | NAd | NAe | 77% at 2 yearsf | NAg | 15% at 3 yearsh |
| Findings and Comments: | ||||||||
| . | Laughlin et al7 . | Sanz et al8 . | Rocha et al7,9 (Eurocord) . | Goldberg et al10 . | Cornetta et al11 (COBLT) . | Ooi et al12 . | Ooi et al13 . | Long et al14 . |
|---|---|---|---|---|---|---|---|---|
| a EFS is better in patients receiving graft with CD34+ cells >1.2 × 105/kg. | ||||||||
| b Patients under the age of 30 had significantly better survival. | ||||||||
| c100 day TRM is lower in patients with disease in chronic phase or remission, N.C.dose infused ≥ 2.0 × 107/kg and transplant performed after January 1998. | ||||||||
| d 10 patients received ex vivo expanded UCBT. | ||||||||
| e The high mortality and relapse reflects the poor risk patients enrolled. | ||||||||
| f All de novo AML. | ||||||||
| g All except 1 patients received UCB transplant as an upfront treatment and all patients received > 2 × 107 N.C. per weight, perhaps due to smaller size of patients (median weight 51 kg). | ||||||||
| h CD34+ cell dose infused correlated with rate of platelet recovery and age > 31 years was significant predictor of poorer event-free survival. | ||||||||
| *19 of the 57 patients were included in the study published by Laughlin et al.7 | ||||||||
| ** platelet > 50,000/μL | ||||||||
| *** All had MDS-related secondary acute myeloid leukemia | ||||||||
| **** 9 of 12 evaluable patients had acute acute graft-versus-host disease. | ||||||||
| Abbreviations: NA, not available; TRM, therapy-related mortality; N.C., nucleated cell dose; TAI , thoraco-abdominal radiation; Ara-C, cytarabine arabinoside; TBI, total body irradiation; ATG, antithymocyte globulin; Bu, bulsulfan; Cy, cyclophosphamide; Thio, thiotepa; Flu, fludarabine; Mel, melphalan; Pred, prednisone; CSA, MTX, methotrexate; GVHD, graft-versus-host disease; MDS, myelodysplastic syndrome | ||||||||
| Number of patients | 68 | 22 | 108 | 19 | 34 | 18 | 13 | 57* |
| Median Age (range, years) | 31.4 (17.6–58.1) | 29 (18–46) | 26 (15–53) | 48 (20–59) | 34.5 (18.2–55) | 43 (21–52) | 40 (20–51) | 31 (18–58) |
| Median weight (range, kg) | 69.2 (40.9–115.5) | 70 (41–85) | 60 (35–110) | 69 (52–126) | NA | 55.2 (NA) | 51 (43–68) | 70 (46–110) |
| Diseases (n) | ||||||||
| Hematological malignancies | 54 | 21 | 96 | 18 | 32 | 18 | 13 | 50 |
| Bone marrow failure syndrome/MDS | 13 | 1 | 12 | 1 | 2 | 6 | ||
| Number of HLA loci disparity (n) | ||||||||
| 0 | 2 | 1 | 6 | 4 | 1 | 0 | 0 | 2 |
| 0 | 2 | 1 | 6 | 4 | 1 | 0 | 0 | 2 |
| 1 | 18 | 13 | 38 | 8 | 10 | 4 | 4 | 8 |
| ≥ 2 | 48 | 8 | 64 | 7 | 23 | 14 | 9 | 47 |
| Preparative regimen (n) | TBI-based/ATG (n = 51) Bu-based/ATG (n = 14) Others/ATG (n = 4) | Thio/Bu/Cy/ATG (n = 21) Thio/Flu/ATG (n = 1) | NA | Cy/TBI/ATG (n = 13) Mel/TBI/ATG (n = 4) Bu/Cy (n = 2) | Cy/TBI (n = 27) Bu/Mel (n = 7) | TBI/Ara-C/Cy (n = 17) TBI/Ara-C/Flu (n = 1) | Cy/TBI/Ara-C (n = 13) | Cy or Mel with TBI or BU/ ATG n = 41 TAI/Cy/ATG (n = 1) |
| GVHD prophylaxis | CSA/Pred (n = NA) CSA (n = NA) | CSA/Pred (n = 22) | CSA/Pred (n = 77) Others (n = 31) | CSA/Pred (n = 13) FK506/Pred (n = 6) | NA CSA/MTX (n = 16) | CSA (n = 2) | CSA/MTX (n = 13) | CSA (n = 1) CSA/Pred (n = 56) |
| Median time to engraftment (range, days) | ||||||||
| ANC > 500/μL | 27 (13–59) | 22 (13–52) | 32 (13–60) | 28 (NA) | 28.5 (13–55) | 23 (16–41) | 22.5 (19–35) | 26 (12–55) |
| Platelet > 20,000/μL | 58 (35–142) | 69 (49–153) | 129 (26–176) | 56 (NA) | NA | 49 (31–263)** | 49 (30–164)** | 84 (35–167) |
| Probability of myeloid engraftment | 90% by 42 days | 100% at 60 days | 81% by day 60 | 75% by day 60 | 72% at day 60 | 94% | 92% | 80% at day 50 |
| GVHD (n) ( probability, %) | ||||||||
| Acute Grade II–IV | 33 (60%) | 16 (NA) | 44 (38) | NA | 11 (38%) | 10 (55%) | 9**** | 17 (41%) |
| Acute Grade III–IV | 11 (20%) | 7 (NA) | 27 (NA) | NA | 6 (21%) | 1 (6%) | – | 9 (22%) |
| Chronic/patients at risk | 12/33 | 9/10 | 15/58 | NA | NA | 14/18 | 8/11 | 8/25 |
| Median cell dose (range) | ||||||||
| N.C. infused (× 107/kg) | 1.6 (0.6–4) | 1.71 (1.01–4.96) | 1.71(0.2–6) | 1.8 (0.4–5.3) | 1.73 (1.11–3.75) | 2.51 (1.16–5.29) | 2.43 (2.09–4.06) | 1.5 (0.54–2.78) |
| CD34+cells infused (× 105/kg) | 1.2 (0.2–16.7) | 0.79 (0.27–2.60) | NA | NA | NA | NA | NA | 1.37 (0.02–12.45) |
| Therapy-related mortality (%) | 50% at 100 day | 43% at 100 day | 54% at 100 day | NA | NA | 6% | 0% | 56% |
| Survival (%) | NA | NA | 27% at 1 year | 20% for good risk and 21% for poor risk at 1 year | 30% at 180 days | 76% at 2 years | 76.2% at 2 years | 19% at 3 years |
| Event-free survival (%) | 26% at 40 monthsa | 53% at 1yearb | 21% at 1 yearc | NAd | NAe | 77% at 2 yearsf | NAg | 15% at 3 yearsh |
| Findings and Comments: | ||||||||