Patient, donor, and transplant characteristics
| Characteristics . | Evaluable, n . | n (%) . | Overall P value . | P value MRD+ vs MRD− . | |||
|---|---|---|---|---|---|---|---|
| All . | Non-CR . | Hematologic CR . | |||||
| MRD+ . | MRD− . | ||||||
| Total patients | 174 (100) | 52 | 94 | 28 | |||
| Age, median (range), y | 174 | 56 (21-75) | 58 (23-73) | 54 (21-75) | 57 (21-69) | 0.46 | 0.72 |
| Sex | |||||||
| Male | 174 | 74 (43) | 21 (40) | 38 (40) | 15 (54) | 0.43 | 0.31 |
| Female | 100 (57) | 31 (60) | 56 (60) | 13 (46) | |||
| Diagnosis | |||||||
| AML, de novo | 174 | 137 (79) | 39 (75) | 76 (81) | 22 (79) | 0.71 | 1.0 |
| AML-MR | 37 (21) | 13 (25) | 18 (19) | 6 (21) | |||
| NPM1 mutation type | |||||||
| A | 174 | 129 (78) | 38 (76) | 71 (78) | 20 (80) | 0.74 | 0.23 |
| B | 12 (7) | 3 (6) | 8 (9) | 1 (4) | |||
| D | 12 (7) | 3 (6) | 6 (7) | 3 (12) | |||
| Not classified | 21 (12) | 8 (15) | 9 (10) | 4 (14) | |||
| Comutations | |||||||
| FLT3-ITD | 171 | 93 (54) | 29 (57) | 49 (53) | 15 (56) | 0.88 | 0.97 |
| Allelic ratio, >0.5 | 154 | 55 (36) | 10 (23) | 35 (41) | 10 (40) | 0.059 | 0.74 |
| FLT3-TKD | 162 | 17 (10) | 7 (14) | 9 (10) | 1 (4) | 0.41 | 0.70 |
| biCEBPA | 101 | 2 (2) | 1 (3) | 0 (0) | 1 (9) | 0.13 | 0.17 |
| IDH1 | 105 | 11 (10) | 4 (13) | 4 (7) | 3 (18) | 0.37 | 0.19 |
| IDH2 | 105 | 16 (15) | 1 (3) | 13 (22) | 2 (12) | 0.056 | 0.50 |
| DNMT3A | 100 | 47 (47) | 19 (59) | 23 (41) | 5 (42) | 0.24 | 1.0 |
| TP53 | 146 | 1 (0.7) | 0 (0) | 1 (1) | 0 (0) | 0.69 | 1.0 |
| Karyotype | |||||||
| CN-AML | 165 | 146 (88) | 40 (80) | 82 (92) | 24 (92) | 0.26 | 0.83 |
| Complex-aberrant | 6 (4) | 3 (6) | 2 (2) | 1 (4) | |||
| Other | 13 (8) | 7 (14) | 5 (6) | 1 (4) | |||
| ELN 2010 | |||||||
| Favorable | 164 | 67 (41) | 19 (38) | 39 (44) | 9 (36) | 0.32 | 0.43 |
| Intermediate 1 | 80 (49) | 22 (44) | 43 (48) | 15 (60) | |||
| Intermediate 2 | 12 (7) | 7 (14) | 5 (6) | 0 (0) | |||
| Adverse | 5 (3) | 2 (4) | 2 (2) | 1 (4) | |||
| ELN 2017 | |||||||
| Favorable | 156 | 91 (58) | 31 (67) | 48 (55) | 12 (52) | 0.32 | 0.74 |
| Intermediate | 59 (38) | 12 (26) | 37 (43) | 10 (43) | |||
| Adverse | 6 (4) | 3 (7) | 2 (2) | 1 (4) | |||
| MRC classification | |||||||
| Favorable | 165 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.52 | 0.54 |
| Intermediate | 159 (96) | 47 (94) | 87 (98) | 25 (96) | |||
| Adverse | 6 (4) | 3 (6) | 2 (2) | 1 (4) | |||
| Induction chemotherapy | |||||||
| 7 + 3 | 174 | 79 (45) | 17 (33) | 47 (50) | 15 (54) | 0.008 | 0.71 |
| 7 + 3 + midostaurin | 38 (22) | 8 (15) | 22 (23) | 8 (29) | |||
| 7 + 3 + GO | 4 (2) | 3 (6) | 1 (1) | 0 (0) | |||
| s-HAM | 34 (20) | 17 (33) | 13 (14) | 4 (14) | |||
| Other | 17 (10) | 5 (10) | 11 (12) | 1 (3) | |||
| None | 2 (1) | 2 (4) | 0 (0) | 0 (0) | |||
| No. of chemotherapy cycles | |||||||
| Median (range) | 174 | 3 (0-25) | 3 (0-8) | 3 (1-25) | 3 (1-6) | 0.75 | 0.61 |
| FLT3-inhibitor before allo-SCT | |||||||
| Yes | 108 | 42 (39) | 10 (9) | 24 (22) | 8 (28) | 0.6 | 0.85 |
| No | 66 (61) | 24 (22) | 34 (31) | 8 (28) | |||
| Status at allo-SCT | |||||||
| CR1/CRi1 | 174 | 96 (56) | 0 (0) | 71 (76) | 25 (89) | < .0001 | 0.19 |
| CR2/CRi2 | 26 (14) | 0 (0) | 23 (24) | 3 (11) | |||
| Active disease | 52 (30) | 52 (100) | 0 (0) | 0 (0) | |||
| Indication for allo-SCT | |||||||
| Risk profile (ELN) | 174 | 57 (33) | 0 (0) | 41 (44) | 16 (57) | < .0001 | 0.01 |
| PIF | 25 (14) | 20 (38) | 3 (2) | 2 (7) | |||
| Hematologic relapse | 53 (30) | 30 (58) | 20 (22) | 3 (11) | |||
| Molecular relapse | 21 (12) | 0 (0) | 19 (20) | 2 (7) | |||
| Inadequate molecular response | 13 (8) | 0 (0) | 11 (12) | 2 (7) | |||
| Other∗ | 5 (3) | 2 (4) | 0 (0) | 3 (11) | |||
| HCT-CI score | |||||||
| 0 | 174 | 61 (35) | 12 (23) | 41 (44) | 8 (29) | 0.069 | 0.21 |
| 1-2 | 61 (35) | 24 (46) | 25 (27) | 12 (43) | |||
| ≥3 | 52 (30) | 16 (31) | 28 (30) | 8 (29) | |||
| Donor type | |||||||
| SIB-D | 174 | 40 (23) | 11 (21) | 18 (19) | 11 (39) | 0.12 | 0.06 |
| MUD | 83 (48) | 21 (40) | 50 (53) | 12 (43) | |||
| MMUD | 16 (9) | 7 (13) | 6 (6) | 3 (11) | |||
| Haploidentical | 35 (20) | 13 (25) | 20 (21) | 2 (7) | |||
| Donor age, median (range), y | 37 (15-69) | 36 (20-61) | 36 (15-69) | 40 (20-63) | 0.16 | 0.05 | |
| Donor sex | |||||||
| Male | 174 | 132 (76) | 38 (73) | 73 (78) | 21 (75) | 0.82 | 0.97 |
| Female | 42 (24) | 14 (27) | 21 (22) | 7 (25) | |||
| Donor sex match | |||||||
| Patient male/donor female | 174 | 16 (9) | 5 (10) | 8 (9) | 3 (11) | 0.80 | 0.38 |
| Patient female/donor male | 74 (43) | 22 (42) | 43 (46) | 9 (32) | |||
| Match | 84 (48) | 25 (48) | 43 (46) | 16 (57) | |||
| ABO blood group match | 174 | 79 (45) | 17 (33) | 48 (51) | 14 (50) | 0.089 | 1.0 |
| CMV match | 124 (71) | 39 (75) | 72 (77) | 13 (46) | 0.0049 | 0.005 | |
| CMV-negative in positive | 174 | 37 (21) | 12 (23) | 16 (17) | 9 (32) | 0.21 | 0.28 |
| CMV-positive in negative | 13 (7) | 1 (2) | 6 (6) | 6 (21) | 0.01 | 0.03 | |
| Cytoreduction prior conditioning | |||||||
| FLAMSA | 174 | 81 (47) | 32 (62) | 37 (39) | 12 (43) | 0.00021 | 0.47 |
| Other | 17 (10) | 10 (19) | 7 (7) | 0 (0) | |||
| None | 76 (44) | 10 (19) | 50 (53) | 16 (57) | |||
| Conditioning intensity | |||||||
| MAC | 174 | 28 (16) | 8 (15) | 18 (19) | 2 (7) | 0.31 | 0.16 |
| RIC | 146 (84) | 44 (85) | 76 (81) | 26 (93) | |||
| Stem cell source | |||||||
| PBSCs | 174 | 158 (91) | 44 (85) | 87 (93) | 27 (96) | 0.15 | 0.68 |
| BM | 16 (9) | 8 (15) | 7 (7) | 1 (4) | |||
| Median cell dose (range) | |||||||
| NC × 108/kg BW | 174 | 2.66 (1.75-5.1) | 2.66 (1.75-3.4) | 2.70 (2.4-3.4) | 2.2 | 0.56 | 0.25 |
| CD34+ × 106/kg BW | 7.3 (1.4-22.87) | 6.85 (3.6-22.87) | 7.31 (1.4-13.36) | 7.3 (4-16) | 0.76 | 0.68 | |
| In vivo TCD | |||||||
| ATG | 174 | 136 (78) | 38 (73) | 73 (78) | 25 (89) | 0.05 | 0.28 |
| PTCy | 38 (22) | 14 (27) | 21 (22) | 3 (11) | |||
| Characteristics . | Evaluable, n . | n (%) . | Overall P value . | P value MRD+ vs MRD− . | |||
|---|---|---|---|---|---|---|---|
| All . | Non-CR . | Hematologic CR . | |||||
| MRD+ . | MRD− . | ||||||
| Total patients | 174 (100) | 52 | 94 | 28 | |||
| Age, median (range), y | 174 | 56 (21-75) | 58 (23-73) | 54 (21-75) | 57 (21-69) | 0.46 | 0.72 |
| Sex | |||||||
| Male | 174 | 74 (43) | 21 (40) | 38 (40) | 15 (54) | 0.43 | 0.31 |
| Female | 100 (57) | 31 (60) | 56 (60) | 13 (46) | |||
| Diagnosis | |||||||
| AML, de novo | 174 | 137 (79) | 39 (75) | 76 (81) | 22 (79) | 0.71 | 1.0 |
| AML-MR | 37 (21) | 13 (25) | 18 (19) | 6 (21) | |||
| NPM1 mutation type | |||||||
| A | 174 | 129 (78) | 38 (76) | 71 (78) | 20 (80) | 0.74 | 0.23 |
| B | 12 (7) | 3 (6) | 8 (9) | 1 (4) | |||
| D | 12 (7) | 3 (6) | 6 (7) | 3 (12) | |||
| Not classified | 21 (12) | 8 (15) | 9 (10) | 4 (14) | |||
| Comutations | |||||||
| FLT3-ITD | 171 | 93 (54) | 29 (57) | 49 (53) | 15 (56) | 0.88 | 0.97 |
| Allelic ratio, >0.5 | 154 | 55 (36) | 10 (23) | 35 (41) | 10 (40) | 0.059 | 0.74 |
| FLT3-TKD | 162 | 17 (10) | 7 (14) | 9 (10) | 1 (4) | 0.41 | 0.70 |
| biCEBPA | 101 | 2 (2) | 1 (3) | 0 (0) | 1 (9) | 0.13 | 0.17 |
| IDH1 | 105 | 11 (10) | 4 (13) | 4 (7) | 3 (18) | 0.37 | 0.19 |
| IDH2 | 105 | 16 (15) | 1 (3) | 13 (22) | 2 (12) | 0.056 | 0.50 |
| DNMT3A | 100 | 47 (47) | 19 (59) | 23 (41) | 5 (42) | 0.24 | 1.0 |
| TP53 | 146 | 1 (0.7) | 0 (0) | 1 (1) | 0 (0) | 0.69 | 1.0 |
| Karyotype | |||||||
| CN-AML | 165 | 146 (88) | 40 (80) | 82 (92) | 24 (92) | 0.26 | 0.83 |
| Complex-aberrant | 6 (4) | 3 (6) | 2 (2) | 1 (4) | |||
| Other | 13 (8) | 7 (14) | 5 (6) | 1 (4) | |||
| ELN 2010 | |||||||
| Favorable | 164 | 67 (41) | 19 (38) | 39 (44) | 9 (36) | 0.32 | 0.43 |
| Intermediate 1 | 80 (49) | 22 (44) | 43 (48) | 15 (60) | |||
| Intermediate 2 | 12 (7) | 7 (14) | 5 (6) | 0 (0) | |||
| Adverse | 5 (3) | 2 (4) | 2 (2) | 1 (4) | |||
| ELN 2017 | |||||||
| Favorable | 156 | 91 (58) | 31 (67) | 48 (55) | 12 (52) | 0.32 | 0.74 |
| Intermediate | 59 (38) | 12 (26) | 37 (43) | 10 (43) | |||
| Adverse | 6 (4) | 3 (7) | 2 (2) | 1 (4) | |||
| MRC classification | |||||||
| Favorable | 165 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.52 | 0.54 |
| Intermediate | 159 (96) | 47 (94) | 87 (98) | 25 (96) | |||
| Adverse | 6 (4) | 3 (6) | 2 (2) | 1 (4) | |||
| Induction chemotherapy | |||||||
| 7 + 3 | 174 | 79 (45) | 17 (33) | 47 (50) | 15 (54) | 0.008 | 0.71 |
| 7 + 3 + midostaurin | 38 (22) | 8 (15) | 22 (23) | 8 (29) | |||
| 7 + 3 + GO | 4 (2) | 3 (6) | 1 (1) | 0 (0) | |||
| s-HAM | 34 (20) | 17 (33) | 13 (14) | 4 (14) | |||
| Other | 17 (10) | 5 (10) | 11 (12) | 1 (3) | |||
| None | 2 (1) | 2 (4) | 0 (0) | 0 (0) | |||
| No. of chemotherapy cycles | |||||||
| Median (range) | 174 | 3 (0-25) | 3 (0-8) | 3 (1-25) | 3 (1-6) | 0.75 | 0.61 |
| FLT3-inhibitor before allo-SCT | |||||||
| Yes | 108 | 42 (39) | 10 (9) | 24 (22) | 8 (28) | 0.6 | 0.85 |
| No | 66 (61) | 24 (22) | 34 (31) | 8 (28) | |||
| Status at allo-SCT | |||||||
| CR1/CRi1 | 174 | 96 (56) | 0 (0) | 71 (76) | 25 (89) | < .0001 | 0.19 |
| CR2/CRi2 | 26 (14) | 0 (0) | 23 (24) | 3 (11) | |||
| Active disease | 52 (30) | 52 (100) | 0 (0) | 0 (0) | |||
| Indication for allo-SCT | |||||||
| Risk profile (ELN) | 174 | 57 (33) | 0 (0) | 41 (44) | 16 (57) | < .0001 | 0.01 |
| PIF | 25 (14) | 20 (38) | 3 (2) | 2 (7) | |||
| Hematologic relapse | 53 (30) | 30 (58) | 20 (22) | 3 (11) | |||
| Molecular relapse | 21 (12) | 0 (0) | 19 (20) | 2 (7) | |||
| Inadequate molecular response | 13 (8) | 0 (0) | 11 (12) | 2 (7) | |||
| Other∗ | 5 (3) | 2 (4) | 0 (0) | 3 (11) | |||
| HCT-CI score | |||||||
| 0 | 174 | 61 (35) | 12 (23) | 41 (44) | 8 (29) | 0.069 | 0.21 |
| 1-2 | 61 (35) | 24 (46) | 25 (27) | 12 (43) | |||
| ≥3 | 52 (30) | 16 (31) | 28 (30) | 8 (29) | |||
| Donor type | |||||||
| SIB-D | 174 | 40 (23) | 11 (21) | 18 (19) | 11 (39) | 0.12 | 0.06 |
| MUD | 83 (48) | 21 (40) | 50 (53) | 12 (43) | |||
| MMUD | 16 (9) | 7 (13) | 6 (6) | 3 (11) | |||
| Haploidentical | 35 (20) | 13 (25) | 20 (21) | 2 (7) | |||
| Donor age, median (range), y | 37 (15-69) | 36 (20-61) | 36 (15-69) | 40 (20-63) | 0.16 | 0.05 | |
| Donor sex | |||||||
| Male | 174 | 132 (76) | 38 (73) | 73 (78) | 21 (75) | 0.82 | 0.97 |
| Female | 42 (24) | 14 (27) | 21 (22) | 7 (25) | |||
| Donor sex match | |||||||
| Patient male/donor female | 174 | 16 (9) | 5 (10) | 8 (9) | 3 (11) | 0.80 | 0.38 |
| Patient female/donor male | 74 (43) | 22 (42) | 43 (46) | 9 (32) | |||
| Match | 84 (48) | 25 (48) | 43 (46) | 16 (57) | |||
| ABO blood group match | 174 | 79 (45) | 17 (33) | 48 (51) | 14 (50) | 0.089 | 1.0 |
| CMV match | 124 (71) | 39 (75) | 72 (77) | 13 (46) | 0.0049 | 0.005 | |
| CMV-negative in positive | 174 | 37 (21) | 12 (23) | 16 (17) | 9 (32) | 0.21 | 0.28 |
| CMV-positive in negative | 13 (7) | 1 (2) | 6 (6) | 6 (21) | 0.01 | 0.03 | |
| Cytoreduction prior conditioning | |||||||
| FLAMSA | 174 | 81 (47) | 32 (62) | 37 (39) | 12 (43) | 0.00021 | 0.47 |
| Other | 17 (10) | 10 (19) | 7 (7) | 0 (0) | |||
| None | 76 (44) | 10 (19) | 50 (53) | 16 (57) | |||
| Conditioning intensity | |||||||
| MAC | 174 | 28 (16) | 8 (15) | 18 (19) | 2 (7) | 0.31 | 0.16 |
| RIC | 146 (84) | 44 (85) | 76 (81) | 26 (93) | |||
| Stem cell source | |||||||
| PBSCs | 174 | 158 (91) | 44 (85) | 87 (93) | 27 (96) | 0.15 | 0.68 |
| BM | 16 (9) | 8 (15) | 7 (7) | 1 (4) | |||
| Median cell dose (range) | |||||||
| NC × 108/kg BW | 174 | 2.66 (1.75-5.1) | 2.66 (1.75-3.4) | 2.70 (2.4-3.4) | 2.2 | 0.56 | 0.25 |
| CD34+ × 106/kg BW | 7.3 (1.4-22.87) | 6.85 (3.6-22.87) | 7.31 (1.4-13.36) | 7.3 (4-16) | 0.76 | 0.68 | |
| In vivo TCD | |||||||
| ATG | 174 | 136 (78) | 38 (73) | 73 (78) | 25 (89) | 0.05 | 0.28 |
| PTCy | 38 (22) | 14 (27) | 21 (22) | 3 (11) | |||
BW, body weight; CMV, cytomegalovirus; CN, cytogenetically normal; CRi, CR with incomplete remission; FLAMSA, chemotherapy regimen consisting of fludarabine, amsacrine, and cytarabine; GO, gemtuzumab ozogamicin; HCT-CI, hematopoietic cell transplantation–specific comorbidity index; kg, kilogram; IDH, isocitrate dehydrogenase; MAC, myeloablative conditioning; MR, myelodysplasia-related changes; MRC, Medical Research Council; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; NC, nucleated cells; NPM1, nucleophosmin; PBSCs, peripheral blood stem cells, PIF, primary induction failure; RIC, reduced intensity conditioning; s-HAM, sequential high-dose cytarabine plus mitoxantrone; SIB-D, sibling donor; TCD, T-cell depletion; TKD, tyrosine kinase domain; 7+3, combination of cytarabine with daunorubicin.
Other causes comprised: secondary AML (n = 3); BM failure after induction treatment (n = 1); and patient request in a patient with favorable risk profile according to ELN.