Table 6.
Studies reporting clinical outcome of karyotypically normal AML patients according to the changes in gene expression
| Prognostic significance | Independent prognostic factor on MVA | AML type | No. of pts (no. with/no. without alteration)* | Age range, y (median) | Median follow-up | Differences in pretreatment features | References |
|---|---|---|---|---|---|---|---|
| BAALC high expression versus BAALC low expression | |||||||
| CR rate: no significant difference (77% vs 81%) | — | De novo | 86 (43/43) | 18-59 (51/56)† | 3.3 y | Lower WBC, less often FAB M5 | Baldus et al20 |
| OS: significantly shorter for high BAALC pts (median, 1.7 vs 5.8 y; P = .02) | Yes | 86 (43/43) | |||||
| EFS: significantly shorter for high BAALC pts (median, 0.8 vs 4.9 y; P = .03) | Yes | 86 (43/43) | |||||
| DFS: significantly shorter for high BAALC pts (median, 1.4 vs 7.3 y; P = .03) | Yes | 68 (33/35) | |||||
| CR rate: no significant difference (82% vs 91%) | — | De novo (84%), secondary (16%) | 67 (44/23) | 18-71 (46/53)† | 38 mo | Higher CD34; lower CD11b, CD15, and MPO‡ | Bienz et al46 |
| OS: significantly shorter for high BAALC pts (median, 10 vs 21 mo; P = .021) | Yes | 67 (44/23) | |||||
| DFS: significantly shorter for high BAALC (median, 8.5 vs 21 mo; P = .015) | Yes | 57 (36/21) | |||||
| CR rate: significantly lower for high BAALC pts (62% vs 73%; P = .038) | No | De novo (91%), secondary (9%) | 307 (153/154) | 17-60 (46/50)† | 29 mo | Higher percentage of PB blasts, more FAB M0/M1, less FAB M5b, less gingival hyperplasia | Baldus et al59 |
| Primary resistant disease rate: significantly higher for high BAALC pts (16% vs 6%; P = .006) | Yes | 307 (153/154) | |||||
| OS: significantly shorter for high BAALC pts (3-year OS rates, 36% vs 54%; P = .001) | Yes | 307 (153/154) | |||||
| RR: significantly higher for high BAALC pts (43% vs 29%; P = .042) | ND | 208 (95/113) | |||||
| CIR: significantly higher for high BAALC pts (3-year CIR rates, 50% vs 32%; P = .018) | Yes | 208 (95/113) | |||||
| BAALC high expression/FLT3 high risk versus BAALC high expression/FLT3 low risk versus BAALC low expression/FLT3 high risk versus BAALC low expression/FLT3 low risk | |||||||
| CR rate: the lowest for BAALC high/FLT3 high-risk pts (57% vs 58% vs 83% vs 73%; P = .048) | ND | De novo and secondary | 268 (21/110/12/125)§ | 17-60 | 29 mo | NR | Baldus et al59 |
| OS: the worst for BAALC high/FLT3 high-risk pts (3-year OS rates, 0% vs 38% vs 22% vs 58%; P < .001) | ND | 268 (21/110/12/125)§ | |||||
| CIR: the highest for BAALC high/FLT3 high-risk pts (3-year CIR rates, 100% vs 44% vs 60% vs 28%; P < .001) | ND | 177 (12/64/10/91)§ | |||||
| ERG high expression versus ERG low expression | |||||||
| CR rate: no significant difference (76% vs 83%) | — | De novo | 48 (21/63) | 18-59 (48/47)‖ | 5.7 y | Higher percentage of PB and BM blasts, more often high BAALC expression | Marcucci et al16 |
| OS: significantly shorter for high ERG pts (median, 1.2 y vs not reached; P = .011) | Yes | 84 (21/63) | |||||
| CIR: significantly higher for high ERG pts (median, 0.7 y vs not reached, P < .001) | Yes | 68 (16/52) | |||||
| Wild-type FLT3 high expression versus wild-type FLT3 low expression | |||||||
| OS: a trend towards worse OS for high FLT3 pts (P = .059) | ND | De novo and secondary | 49 (21/28) | 17-84 (61)¶ | NR | NR | Kuchenbauer et al66 |
| EFS: a trend towards worse EFS for high FLT3 pts (P = .087) | ND | 50 (21/29) | |||||
| MN1 high expression versus MN1 low expression | |||||||
| CR rate: no significant difference (80 vs 89%) | — | De novo (87%), secondary (13%) | 142 (71/71) | 18-60 (46/45)# | 30 mo | Less often mutated NPM1, less often NPM1 mutated/FLT3-ITD absent, more often high CD34 expression | Heuser et al15 |
| OS: significantly shorter for high MN1 pts (3-year OS rates, 38.1% vs 58.8%; P = .03) | Yes | 142 (71/71) | |||||
| RFS: significantly shorter for high MN1 pts (3-year RFS rates, 23.4% vs. 51.4%; P = .002) | Yes | 120 (57/63) | |||||
| RR: significantly higher for high MN1 pts (56.1% vs 36.5%; P = .03) | — | 120 (57/63) |
MVA indicates multivariable analysis; pts, patients; CR, complete remission; OS, overall survival; EFS, event-free survival; DFS, disease-free survival; RR, risk of relapse; CIR, cumulative incidence of relapse; FLT3 high risk, patients with a high (ie, more than 0.8) FLT3-ITD/FLT3-wild-type allele ratio; FLT3 low risk, patients with FLT3 wild-type alleles or a low (ie, equal to or less than 0.8) FLT3-ITD/FLT3-wild-type allele ratio; RFS, relapse-free survival; —, no significant difference in univariable analysis (MVA not performed); WBC, white blood cell count; FAB, French-American-British; MPO, myeloperoxidase; ND, not done; PB, blood; NR, not reported; and BM; bone marrow.
Numbers of patients for whom clinical data were available.
Median age for patients with high/patients with low BAALC expression.
Differences in pretreatment features significant for comparisons between patients with high (n = 23) and low (n = 15) BAALC expression when patients with FLT3-ITD and CEBPA mutations were excluded.
Number of patients with BAALC high expression/FLT3 high-risk/patients with BAALC high expression/FLT3 low-risk/patients with BAALC low expression/FLT3 high-risk/patients with BAALC low expression/FLT3 low-risk.
Median age for patients with high/patients with low ERG expression.
Age range and median reported for all patients, both with normal and abnormal karyotype.
Mean age for patients with high/patients with low MN1 expression.