Comparison of the WT1 mutation studies performed by AMLSG, CALGB, and MRC
| . | AMLSG . | CALGB . | MRC . |
|---|---|---|---|
| Patients, n | 617 | 196 | 470 |
| Type of AML | De novo, s-AML, t-AML | De novo | 94% de novo AML |
| Age, y | 16-60 | 18-60 | 15-60; 13 patients > 60 |
| Median follow-up time, mo | 33 | 50.4 | 122.4 (range, 27-213) |
| Trials | AML HD93, AML HD98-A, AMLSG 07-04 | 9621, 19808 | MRC10, MRC12 |
| Exons | 1-10 | 7 and 9 | 7 and 9 |
| No. of mutated patients | 78/617 (13%) | 21/196 (11%) | 47/470 (10%) |
| Associated mutations (WT1mut) | FLT3-ITD (P = .001) CEBPAmut (P = .004) NPM1mut (inverse, P = .001) | FLT3-ITD (P = .06) | FLT3-ITD (P = .08) NPM1mut (inverse, P = .05) |
| Clinical characteristics (WT1mut) | ↓ age (P = .007) ↑ LDH serum levels (P = .007) ↑ PB blast counts (P = .01) | ↑ WBC counts (P = .01) | No difference in age, sex, type of AML, WBC count |
| Response to induction (WT1mut) | No difference in rate of CR, RD, and ED | No difference in rate of CR | Inferior response to induction therapy (P = .02) |
| Survival analysis (WT1mut) | |||
| Univariable analysis | No difference in RFS and OS | ↓ DFS (P < .001), ↓ OS (P < .001) | ↓ RFS (P = .005), ↓ OS (P = .007) |
| Multivariable analysis | No difference in RFS and OS | ↓ DFS (P = .009), ↓ OS (P < .001) | ↓ RFS (P < .02), ↓ OS (P < .04) |
| Explorative subset analysis | WT1mut/FLT3-ITDneg: ↑ CR (92%), ↓ RD (5%) WT1mut/FLT3-ITDpos: ↓ CR (63%), ↑ RD (33%) ↓ RFS (P = .006), ↓ OS (P < .001) | Not performed | Not performed |
| Cumulative dosages of high-dose cytarabine | 18-54 g/m2 | 13-25 g/m2 | 1-8 g/m2 |
| . | AMLSG . | CALGB . | MRC . |
|---|---|---|---|
| Patients, n | 617 | 196 | 470 |
| Type of AML | De novo, s-AML, t-AML | De novo | 94% de novo AML |
| Age, y | 16-60 | 18-60 | 15-60; 13 patients > 60 |
| Median follow-up time, mo | 33 | 50.4 | 122.4 (range, 27-213) |
| Trials | AML HD93, AML HD98-A, AMLSG 07-04 | 9621, 19808 | MRC10, MRC12 |
| Exons | 1-10 | 7 and 9 | 7 and 9 |
| No. of mutated patients | 78/617 (13%) | 21/196 (11%) | 47/470 (10%) |
| Associated mutations (WT1mut) | FLT3-ITD (P = .001) CEBPAmut (P = .004) NPM1mut (inverse, P = .001) | FLT3-ITD (P = .06) | FLT3-ITD (P = .08) NPM1mut (inverse, P = .05) |
| Clinical characteristics (WT1mut) | ↓ age (P = .007) ↑ LDH serum levels (P = .007) ↑ PB blast counts (P = .01) | ↑ WBC counts (P = .01) | No difference in age, sex, type of AML, WBC count |
| Response to induction (WT1mut) | No difference in rate of CR, RD, and ED | No difference in rate of CR | Inferior response to induction therapy (P = .02) |
| Survival analysis (WT1mut) | |||
| Univariable analysis | No difference in RFS and OS | ↓ DFS (P < .001), ↓ OS (P < .001) | ↓ RFS (P = .005), ↓ OS (P = .007) |
| Multivariable analysis | No difference in RFS and OS | ↓ DFS (P = .009), ↓ OS (P < .001) | ↓ RFS (P < .02), ↓ OS (P < .04) |
| Explorative subset analysis | WT1mut/FLT3-ITDneg: ↑ CR (92%), ↓ RD (5%) WT1mut/FLT3-ITDpos: ↓ CR (63%), ↑ RD (33%) ↓ RFS (P = .006), ↓ OS (P < .001) | Not performed | Not performed |
| Cumulative dosages of high-dose cytarabine | 18-54 g/m2 | 13-25 g/m2 | 1-8 g/m2 |
AMLSG denotes German-Austrian AML Study Group; CALGB, Cancer and Leukemia Group B; MRC, Medical Research Council; s-AML, secondary AML; t-AML, therapy-associated AML; WBC, white blood cell; LDH, lactate dehydrogenase; PB, peripheral blood; CR, complete remission; RD, refractory disease; ED, early death; RFS, relapse-free survival; OS, overall survival; and DFS, disease-free survival.