Table 1.
Baseline transplantation characteristics
| All (n = 32) | Group 1: Never cGvHD (n = 10) | Group 2: Resolved cGvHD (n = 11) | Group 3: Active cGvHD (n = 11) | p-value | |
|---|---|---|---|---|---|
| Patient age at the time of transplantation, years | |||||
| Median (IQR) | 39 (26, 47) | 42 (34, 49) | 28 (21, 49) | 40 (31, 48) | .199 |
| Patient age at the time of survey, years | |||||
| Median (IQR) | 53 (37, 62) | 59 (45, 63) | 41 (29, 60) | 54 (36, 62) | .264 |
| Follow-up time, months | |||||
| Median (IQR) | 153 (113, 191) | 174 (103, 231) | 152 (113, 199) | 151 (120, 182) | .623 |
| Gender, n (%) | |||||
| Women | 13 (41.0%) | 3 (30.0%) | 5 (45.5%) | 5 (45.5%) | .712 |
| Men | 19 (59.0%) | 7 (70.0%) | 6 (54.5%) | 6 (54.5%) | |
| Diagnosis, n (%) | |||||
| Primary AML | 22 (68.8%) | 7 (70.0%) | 7 (63.6%) | 8 (72.7%) | .895 |
| Secondary AML | 10 (31.3%) | 3 (30.0%) | 4 (36.4%) | 3 (27.3%) | |
| 2017 European LeukemiaNet genetic risk stratification, n (%) | |||||
| Favorable | 6 (18.8%) | 2 (20.0%) | 3 (27.3%) | 1 (9.1%) | .829 |
| Intermediate | 18 (56.3%) | 6 (60.0%) | 5 (45.5%) | 7 (63.6%) | |
| Adverse | 8 (25.0%) | 2 (20.0%) | 3 (27.3%) | 3 (27.3%) | |
| Remission status at the time of transplantation, n (%) | |||||
| First complete remission (CR1) | 15 (46.9%) | 5 (50.0%) | 4 (36.4%) | 6 (54.5%) | .700 |
| First partial remission (PR1), CR2 | 12 (37.5%) | 3 (30.0%) | 6 (54.5%) | 3 (27.3%) | |
| > CR2, primary refractory AML | 5 (15.6%) | 2 (20.0%) | 1 (9.1%) | 2 (18.2%) | |
| Hematopoietic stem cell transplantation comorbidity index (HCT-CI), n (%) | |||||
| 0 | 16 (50.0%) | 6 (60.0%) | 4 (36.4%) | 6 (54.5%) | .712 |
| 1–2 | 11 (34.4%) | 2 (20.0%) | 5 (45.5%) | 4 (36.4%) | |
| ≥ 3 | 5 (15.6%) | 2 (20.0%) | 2 (18.2%) | 1 (9.1%) | |
| Karnofsky performance score, n (%) | |||||
| < 80 | 4 (12.5%) | 1 (10.0%) | 1 (9.1%) | 2 (18.2%) | .779 |
| ≥ 80 | 28 (87.5%) | 9 (90.0%) | 10 (90.9%) | 9 (81.8%) | |
| Donor type, n (%) | |||||
| Matched sibling donor | 10 (31.3%) | 2 (20.0%) | 3 (27.3%) | 5 (45.5%) | .637 |
| Matched unrelated donor | 17 (53.1%) | 7 (70.0%) | 5 (45.5%) | 5 (45.5%) | |
| Mismatched unrelated donor | 4 (12.5%) | 1 (10.0%) | 2 (18.2%) | 1 (9.1%) | |
| Haploidentical, mismatched related donor | 1 (3.1%) | 0 (-) | 1 (9.1%) | 0 (–) | |
| Stem cell source, n (%) | |||||
| Peripheral blood | 30 (93.8%) | 8 (80.0%) | 11 (100%) | 11 (100%) | .320 |
| Bone marrow | 1 (3.1%) | 1 (10.0%) | 0 (–) | 0 (–) | |
| Cord blood | 1 (3.1%) | 1 (10.0%) | 0 (–) | 0 (–) | |
| Conditioning regimen, n (%) | |||||
| Myeloablative (MAC) | 23 (71.9%) | 8 (80.0%) | 10 (90.9%) | 5 (45.5%) | .047 |
| Reduced intensity (RIC) | 9 (28.1%) | 2 (20.0%) | 1 (9.1%) | 6 (54.5%) | |
| Chemotherapeutic regimen, n (%) | |||||
| 8 Gy TBI/CY2/Fludarabine | 15 (46.9%) | 7 (70.0%) | 5 (45.5%) | 3 (27.3%) | .090 |
| FLAMSA-RIC/CY2/4 Gy TBI | 9 (28.1%) | 2 (20.0%) | 1 (9.1%) | 6 (54.5%) | |
| 12 Gy TBI/CY2 | 5 (15.6%) | 0 (–) | 3 (27.3%) | 2 (18.2%) | |
| 8 Gy TBI/Fludarabine | 3 (9.4%) | 1 (10.0%) | 2 (18.2%) | 0 (–) | |
| GvHD-prophylaxis, n (%) | |||||
| Cyclosporine/MTX | 26 (81.2%) | 9 (90.0%) | 10 (90.9%) | 7 (63.6%) | .322 |
| Cyclosporine/Mycophenolate mofetil | 4 (12.5%) | 1 (10.0%) | 0 (–) | 3 (27.3%) | |
| Post-transplantation Cyclophosphamide/tacrolimus/Mycophenolate mofetil | 2 (6.3%) | 0 (–) | 1 (9.1%) | 1 (9.1%) | |
| Anti-Thymocyte Globulin (ATG), n (%) | |||||
| Yes | 23 (71.9%) | 9 (90.0%) | 9 (81.8%) | 5 (45.5%) | .051 |
| No | 9 (28.1%) | 1 (10.0%) | 2 (18.2%) | 6 (54.5%) | |
| Donor-recipient cytomegalic-virus-status, n (%) | |||||
| Negative/negative | 16 (50.0%) | 5 (50.0%) | 8 (72.7%) | 3 (27.3%) | .143 |
| Negative/positive | 6 (18.8%) | 1 (10.0%) | 0 (-) | 5 (45.5%) | |
| Positive/positive | 6 (18.8%) | 2 (20.0%) | 2 (18.2%) | 2 (18.2%) | |
| Positive/negative | 4 (12.5%) | 2 (20.0%) | 1 (9.1%) | 1 (9.1%) | |
| Female donor to male recipient, n (%) | |||||
| Yes | 5 (15.6%) | 1 (10.0%) | 2 (18.2%) | 2 (18.2%) | .840 |
| No | 27 (84.4%) | 9 (90.0%) | 9 (81.8%) | 9 (81.8%) | |
| Grade II–IV acute GvHD, n (%) | |||||
| Yes | 12 (37.5%) | 4 (40.0%) | 4 (36.4%) | 4 (36.4%) | .981 |
| No | 20 (62.5%) | 6 (60.0%) | 7 (63.6%) | 7 (63.6%) | |
| Acute GvHD grade (n = 12) | |||||
| Grade II | 9 (75.0%) | 3 (75.0%) | 3 (75.0%) | 3 (75.0%) | .558 |
| Grade III | 2 (16.7%) | 1 (25.0%) | 0 (–) | 1 (25.0%) | |
| Grade IV | 1 (8.3%) | 0 (–) | 1 (25.0%) | 0 (–) | |
| Survival in CR/relapse, n (%) | |||||
| Survival in CR | 29 (90.6%) | 10 (100%) | 9 (81.8%) | 10 (90.9%) | .361 |
| Relapse* | 3 (9.4%) | 0 (-) | 2 (18.2%)¶ | 1 (9.1%) § | |
Never cGvHD (chronic Graft-versus-Host Disease): never having cGvHD; Resolved cGvHD: all signs of clinically activity of cGvHD have disappeared, past history of cGvHD, no use of immunosuppression; Active cGvHD: physician reported inflammatory manifestations of cGvHD
TBI 8 Gy/Cy2/Fludarabine: 8 Gy TBI (four 2 Gy doses on two consecutive days), Cyclophosphamide 2 × 60 mg/kg on two consecutive days, Fludarabine 3 × 30 mg/m2 on three consecutive days
FLAMSA-RIC/TBI 4 Gy/Cy2: FLAMSA regimen (d -12 to d -9): Fludarabine 4 × 30 mg/m2, HD-Ara-C 4 × 2000 mg/m2, Amsacrine 4 × 100 mg/m2. Reduced intensity conditioning (RIC)-regimen after 3 days of rest: 4 Gy TBI on d-5 (two 2 Gy doses), Cyclophosphamide (2 × 40 mg/kg for MRD or 2 × 60 mg/kg for MUD, MMRD or MMUD) on d -4 to d -3 , Antithymocyte globulin 10 mg/kg for MRD or 20 mg/kg for MUD, MMRD, MMUD from d-4 to d-2, prophylactic donor lymphocyte infusions at day + 120 or 30 days after discontinuation of immunosuppression: 1–5 × 106 CD3+ cells/kg
TBI 12 Gy/Cy2: 12 Gy TBI (Six 2 Gy doses on three consecutive days, d -7 to d -5), Cyclophosphamide 2 × 60 mg/kg on 2 consecutive days (d -4 to d -3)
TBI 8 Gy/Fludarabine: 8 Gy TBI (four 2 Gy doses on 2 consecutive days, d-5 and d-4), Fludarabine 4 × 30 mg/m2 (d -5 to d -2)
*At time of the evaluation: All patients with relapse in history were in complete remission of the initial diagnosed AML after donor lymphocyte infusions (n = 2 ¶) and therapy with azacitidine (n = 1 §) for a median time of 43.8 months (IQR 34.0, 98.6 months)