Patients' characteristics and important clinical data
. | Case 1 . | Case 2 . | Case 3 . |
|---|---|---|---|
| Age, y | 53 | 22 | 58 |
| Sex, patient/donor | Female/female | Male/male | Male/female |
| Diagnosis | CML | CML | MDS |
| Conditioning, mg/kg BW | |||
| Busulfan | 14 | 14 | 12 |
| Cyclophosphamide | 120 | 120 | 120 |
| VP16 | — | — | 30 |
| PBSCT type | Matched related donor | Matched related donor | Matched related donor |
| Mismatches | 1: HLA-A | No | No |
| CD34+ dose/kg | 4.22 × 106 | 4.6 × 106 | 4.3 × 106 |
| Contaminating CD3+ cells | 2 × 103/kg | 1 × 104/kg | 3.6 × 104/kg |
| SGM T cells, CD3+/kg | 4.8 × 106 | 5.46 × 106 | 4.9 × 106 |
| Second infusion (d) | 4.8 × 106 (65) | 5.46 × 106 (58) | No* |
| GvHD prophylaxis | Cyclosporin A | Cyclosporin A | Cyclosporin A |
| Beginning d | −1 | −1 | −1 |
| GvHD (overall grade/d) | Yes (1/23) | No | Yes (11/14) |
| GCV treatment (d) | No | No | Yes (17-26) |
| Outcome | Resolved spontaneously | NA | Resolution |
| Engraftment (chimerism) | Yes (full) | Yes (full) | Yes (full) |
| Neutrophils, d | 11 | 12 | 13 |
| Platelets, d | 10 | 13 | 16 |
| SGM T cells in vivo | Early loss (d 23) after 2nd infusion; only present for 2 d | Present for more than 3 mo | Loss after GCV treatment (d 25) |
| Special remarks | HSV infection during transplantation | Increasing bcr/abl levels at ≈ 1 y | — |
| Clinical outcome | Secondary graft failure (d 156); 2nd allo-PBSCT; severe complications; patient died | DLI for MRD (1 × 107 kg) at 1 y 3 m, alive/well | Secondary graft failure (d 119); 2nd allo-PBSCT; severe complications; patient died |
. | Case 1 . | Case 2 . | Case 3 . |
|---|---|---|---|
| Age, y | 53 | 22 | 58 |
| Sex, patient/donor | Female/female | Male/male | Male/female |
| Diagnosis | CML | CML | MDS |
| Conditioning, mg/kg BW | |||
| Busulfan | 14 | 14 | 12 |
| Cyclophosphamide | 120 | 120 | 120 |
| VP16 | — | — | 30 |
| PBSCT type | Matched related donor | Matched related donor | Matched related donor |
| Mismatches | 1: HLA-A | No | No |
| CD34+ dose/kg | 4.22 × 106 | 4.6 × 106 | 4.3 × 106 |
| Contaminating CD3+ cells | 2 × 103/kg | 1 × 104/kg | 3.6 × 104/kg |
| SGM T cells, CD3+/kg | 4.8 × 106 | 5.46 × 106 | 4.9 × 106 |
| Second infusion (d) | 4.8 × 106 (65) | 5.46 × 106 (58) | No* |
| GvHD prophylaxis | Cyclosporin A | Cyclosporin A | Cyclosporin A |
| Beginning d | −1 | −1 | −1 |
| GvHD (overall grade/d) | Yes (1/23) | No | Yes (11/14) |
| GCV treatment (d) | No | No | Yes (17-26) |
| Outcome | Resolved spontaneously | NA | Resolution |
| Engraftment (chimerism) | Yes (full) | Yes (full) | Yes (full) |
| Neutrophils, d | 11 | 12 | 13 |
| Platelets, d | 10 | 13 | 16 |
| SGM T cells in vivo | Early loss (d 23) after 2nd infusion; only present for 2 d | Present for more than 3 mo | Loss after GCV treatment (d 25) |
| Special remarks | HSV infection during transplantation | Increasing bcr/abl levels at ≈ 1 y | — |
| Clinical outcome | Secondary graft failure (d 156); 2nd allo-PBSCT; severe complications; patient died | DLI for MRD (1 × 107 kg) at 1 y 3 m, alive/well | Secondary graft failure (d 119); 2nd allo-PBSCT; severe complications; patient died |
CML indicates chronic myelogenous leukemia; MDS, myelodysplastic syndrome; PBSCT, peripheral blood stem cell transplantation; GCV, ganciclovir; NA, not applicable; DLI, donor leukocyte infusion; MRD, minimal residual disease.
The protocol allowed a second infusion of 1 to 5 × 106/kg SGM donor T cells on day 60 only if no GvHD higher than grade 1 had developed.