Demographics and main clinico-diagnostic characteristics of 572 patients randomly assigned to receive induction chemotherapy with either ICE or sHD
| Patient characteristics . | All patients (N = 572) . | ICE (N = 286) . | sHD (N = 286) . | P . |
|---|---|---|---|---|
| Age (at randomization), median (range), y | 52 (16-73) | 53 (16-73) | 50 (18-72) | .34 |
| >60 y, n (%) | 140 (24.5) | 73 (25.5) | 67 (23.4) | .55 |
| Sex | ||||
| Male, n (%) | 301 (52.6) | 156 (54.5) | 145 (50.7) | .35 |
| Diagnosis, n (%) | ||||
| AML morphological subtype* | .82 | |||
| SR | 478 (83.6) | 240 (83.9) | 238 (83.2) | |
| HR | 94 (16.4) | 46 (16.1) | 48 (16.8) | |
| HR MDS | 6 (1.0) | 3 (1.0) | 3 (1.0) | |
| AML category | .80 | |||
| De novo | 494 (86.4) | 248 (86.7) | 246 (86.0) | |
| Non de novo† | 78 (13.6) | 38 (13.3) | 40 (14.0) | |
| ECOG PS, n (%) | .01 | |||
| 0 | 292 (51.1) | 130 (45.5) | 162 (56.6) | |
| 1 | 232 (40.6) | 134 (46.9) | 98 (34.3) | |
| 2 | 42 (7.3) | 19 (6.6) | 23 (8.0) | |
| 3 | 6 (1.0) | 3 (1.0) | 3 (1.0) | |
| Clinical features, n (%) | ||||
| Hepatomegaly | 42 (7.3) | 20 (7.0) | 22 (7.7) | .74 |
| Splenomegaly | 65 (11.4) | 29 (10.1) | 36 (12.6) | .35 |
| Extramedullary involvement | 71 (12.4) | 34 (11.9) | 37 (12.9) | .70 |
| Hematology, median (range) | ||||
| Hemoglobin, g/dL | 9.1 (3-15.8) | 9.3 (3.6-14.8) | 8.9 (3-15.8) | .82 |
| WBC, ×109/L | 10.5 (0.5-990) | 12.3 (0.5-990) | 9.2 (0.6-260) | .10 |
| Platelets, ×109/L | 53 (2-852) | 53 (2-815) | 53.5 (3-852) | .74 |
| Peripheral blood blast cells, % | 47.5 (0-100) | 46 (0-100) | 48 (0-100) | .94 |
| Bone marrow blast cells, % | 77 (0-100) | 80 (6-100) | 74.5 (0-100) | .18 |
| Cytogenetics, n (%) | ||||
| Favorable | 52 (9.1) | 23 (8.0) | 29 (10.1) | .59 |
| t(8;21)‡ | 20 (3.5) | 10 (3.5) | 10 (3.5) | |
| inv(16)§,‖ | 32 (5.6) | 13 (4.5) | 19 (6.6) | |
| Intermediate | ||||
| Normal karyotype | 272 (47.6) | 142 (49.7) | 130 (45.5) | .31 |
| Abnormal¶ | 9 (1.6) | 4 (1.4) | 5 (1.7) | .08 |
| Adverse# | 170 (29.7) | 82 (28.7) | 88 (30.8) | .52 |
| Other | 12 (2.1) | 6 (2.1) | 6 (2.1) | 1.0 |
| Unknown | 57 (10.0) | 29 (10.1) | 28 (9.8) | .88 |
| Genetics, n (%) | ||||
| MLL-rearrangement | 24/397 (6.0) | 10/200 (5.0) | 14/197 (7.1) | .65 |
| FLT3-ITD+ | 103/569 (18.1) | 55/284 (19.4) | 48/285 (16.8) | .58 |
| FLT3-PM+ | 40/555 (7.2) | 22/275 (8.0) | 18/280 (6.4) | .36 |
| NPM1+ | 167/551 (30.3) | 87/277 (31.4) | 80/274 (29.2) | .68 |
| CBFB-MYH11+‖ | 41/557 (7.4) | 16/278 (5.8) | 25/279 (9.0) | .33 |
| AML1/ETO+‡ | 27/558 (4.8) | 15/277 (5.4) | 12/281 (4.3) | .45 |
| CEBPA+ | 19/361 (5.3) | 8/182 (4.4) | 11/179 (6.1) | .60 |
| NILG risk group, n (%)** | .13 | |||
| SR | 156 (27.3) | 70 (24.5) | 86 (30.1) | |
| HR | 416 (72.7) | 216 (75.5) | 200 (69.9) | |
| ELN 2010 risk group, n (%) | .56 | |||
| Favorable | 166 (29.0) | 82 (28.7) | 84 (29.4) | |
| Intermediate 1 | 147 (25.7) | 80 (28.0) | 67 (23.4) | |
| Intermediate 2 | 70 (12.2) | 36 (1.6) | 34 (11.9) | |
| Adverse | 135 (23.6) | 60 (21.0) | 75 (26.2) | |
| Unknown | 54 (9.4) | 28 (9.8) | 26 (9.1) |
| Patient characteristics . | All patients (N = 572) . | ICE (N = 286) . | sHD (N = 286) . | P . |
|---|---|---|---|---|
| Age (at randomization), median (range), y | 52 (16-73) | 53 (16-73) | 50 (18-72) | .34 |
| >60 y, n (%) | 140 (24.5) | 73 (25.5) | 67 (23.4) | .55 |
| Sex | ||||
| Male, n (%) | 301 (52.6) | 156 (54.5) | 145 (50.7) | .35 |
| Diagnosis, n (%) | ||||
| AML morphological subtype* | .82 | |||
| SR | 478 (83.6) | 240 (83.9) | 238 (83.2) | |
| HR | 94 (16.4) | 46 (16.1) | 48 (16.8) | |
| HR MDS | 6 (1.0) | 3 (1.0) | 3 (1.0) | |
| AML category | .80 | |||
| De novo | 494 (86.4) | 248 (86.7) | 246 (86.0) | |
| Non de novo† | 78 (13.6) | 38 (13.3) | 40 (14.0) | |
| ECOG PS, n (%) | .01 | |||
| 0 | 292 (51.1) | 130 (45.5) | 162 (56.6) | |
| 1 | 232 (40.6) | 134 (46.9) | 98 (34.3) | |
| 2 | 42 (7.3) | 19 (6.6) | 23 (8.0) | |
| 3 | 6 (1.0) | 3 (1.0) | 3 (1.0) | |
| Clinical features, n (%) | ||||
| Hepatomegaly | 42 (7.3) | 20 (7.0) | 22 (7.7) | .74 |
| Splenomegaly | 65 (11.4) | 29 (10.1) | 36 (12.6) | .35 |
| Extramedullary involvement | 71 (12.4) | 34 (11.9) | 37 (12.9) | .70 |
| Hematology, median (range) | ||||
| Hemoglobin, g/dL | 9.1 (3-15.8) | 9.3 (3.6-14.8) | 8.9 (3-15.8) | .82 |
| WBC, ×109/L | 10.5 (0.5-990) | 12.3 (0.5-990) | 9.2 (0.6-260) | .10 |
| Platelets, ×109/L | 53 (2-852) | 53 (2-815) | 53.5 (3-852) | .74 |
| Peripheral blood blast cells, % | 47.5 (0-100) | 46 (0-100) | 48 (0-100) | .94 |
| Bone marrow blast cells, % | 77 (0-100) | 80 (6-100) | 74.5 (0-100) | .18 |
| Cytogenetics, n (%) | ||||
| Favorable | 52 (9.1) | 23 (8.0) | 29 (10.1) | .59 |
| t(8;21)‡ | 20 (3.5) | 10 (3.5) | 10 (3.5) | |
| inv(16)§,‖ | 32 (5.6) | 13 (4.5) | 19 (6.6) | |
| Intermediate | ||||
| Normal karyotype | 272 (47.6) | 142 (49.7) | 130 (45.5) | .31 |
| Abnormal¶ | 9 (1.6) | 4 (1.4) | 5 (1.7) | .08 |
| Adverse# | 170 (29.7) | 82 (28.7) | 88 (30.8) | .52 |
| Other | 12 (2.1) | 6 (2.1) | 6 (2.1) | 1.0 |
| Unknown | 57 (10.0) | 29 (10.1) | 28 (9.8) | .88 |
| Genetics, n (%) | ||||
| MLL-rearrangement | 24/397 (6.0) | 10/200 (5.0) | 14/197 (7.1) | .65 |
| FLT3-ITD+ | 103/569 (18.1) | 55/284 (19.4) | 48/285 (16.8) | .58 |
| FLT3-PM+ | 40/555 (7.2) | 22/275 (8.0) | 18/280 (6.4) | .36 |
| NPM1+ | 167/551 (30.3) | 87/277 (31.4) | 80/274 (29.2) | .68 |
| CBFB-MYH11+‖ | 41/557 (7.4) | 16/278 (5.8) | 25/279 (9.0) | .33 |
| AML1/ETO+‡ | 27/558 (4.8) | 15/277 (5.4) | 12/281 (4.3) | .45 |
| CEBPA+ | 19/361 (5.3) | 8/182 (4.4) | 11/179 (6.1) | .60 |
| NILG risk group, n (%)** | .13 | |||
| SR | 156 (27.3) | 70 (24.5) | 86 (30.1) | |
| HR | 416 (72.7) | 216 (75.5) | 200 (69.9) | |
| ELN 2010 risk group, n (%) | .56 | |||
| Favorable | 166 (29.0) | 82 (28.7) | 84 (29.4) | |
| Intermediate 1 | 147 (25.7) | 80 (28.0) | 67 (23.4) | |
| Intermediate 2 | 70 (12.2) | 36 (1.6) | 34 (11.9) | |
| Adverse | 135 (23.6) | 60 (21.0) | 75 (26.2) | |
| Unknown | 54 (9.4) | 28 (9.8) | 26 (9.1) |
After amendment 3 (September 2009), patients older than 65 years were no longer enrolled into the study.
+, gene rearrangement or mutation; ITD, internal tandem duplication; PM, point mutation; NILG, Northern Italy Leukemia Group; sHD, sequential HD cytarabine/idarubicin; WBC, white blood cell count.
HR: minimally differentiated AML, erythroleukemia, megakaryoblastic leukemia, undifferentiated/bilineal/biphenotypic acute leukemia, acute panmyelosis with myelofibrosis, myeloid sarcoma, AML with multilineage dysplasia, HR MDS (marrow blast cells, 10%-20%); SR, all other morphological and diagnostic subsets.
AML after myelodysplastic or chronic myeloproliferative syndromes, related to another therapy (chemotherapy/radiotherapy for another cancer), or preceded by an antecedent hematologic disorder (unexplained cytopenia).
Total number with either method: 27/572 (4.7%).
inv(16), t(16;16), del(16q).
Total number with either method: 42/572 (7.3%).
Abnormalities included +6, +11, +13, +22, del(12p), t(9;11), -Y.
Adverse abnormalities included −5/del(5q), −7/del(7q), t(11;19)/t(11q23), and MLL gene rearrangements, t(9;22), abn 3q,9q,11q,12p,20q,21q,17p, iso(17q), +8, +21, t(3;3), t(3;5); inv(3), t(6;9), t(6;11), and complex karyotype with 3 or more unrelated clonal markers.
Eleven patients with concurrent favorable and adverse cytogenetics were included in the adverse group, as per protocol design.