Table 2.
Studies reporting clinical outcome of karyotypically normal AML patients according to the FLT3 status
| 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 | Source |
|---|---|---|---|---|---|---|---|
| FLT3-ITD+ versus FLT3-ITD− | |||||||
| CR rate: no significant difference (77% vs 86%) | — | De novo | 82 (23/59) | 20-59 (NR) | 1.7 y | Higher WBC | Whitman et al18 |
| OS: no significant difference (median, 11 vs 46 mo) | — | 82 (23/59) | |||||
| DFS: significantly shorter for FLT3-ITD+ pts (median, 8 vs 52 mo; P = .03) | ND | 68 (17/51) | |||||
| CR rate: no significant difference | — | De novo | 106 (33/73) | 17-65 (44) | NR | NR | Boissel et al37 |
| OS: no significant difference (6-year OS rates, 37% vs 43%) | — | 106 (33/73) | |||||
| EFS: significantly shorter for FLT3-ITD+ pts (5-year EFS rates, 19% vs 34%; P = .05) | No | 106 (33/73) | |||||
| CR rate: no significant difference (84% vs 85%) | — | De novo (84%), secondary (16%) | 67 (19/48) | 18-71 (52/48)‡ | 38 mo | Higher WBC, higher LDH | Bienz et al46 |
| OS: significantly shorter for FLT3-ITD+ pts (median, 10 vs 15.5 mo; P = .015) | Yes | 67 (19/48) | |||||
| DFS: significantly shorter for FLT3-ITD+ pts (median, 8 vs 12.5 mo; P = .033) | Yes | 57 (16/41) | |||||
| CR rate: no significant difference (50% vs 76%) | — | De novo | 53 (16/37) | Adults (58)§ | NR | Higher WBC, higher LDH, lower lactoferrin expression | Kainz et al44 |
| OS: significantly shorter for FLT3-ITD+ pts (5-year OS rates, 6% vs 28%; P < .003) | Yes | 53 (16/37) | |||||
| DFS: significantly shorter for FLT3-ITD+ pts (5-year DFS rates, 13% vs 41%; P < .02) | NR | 36 (8/28) | |||||
| FLT3-ITD+ versus FLT3-WT† | |||||||
| OS: significantly shorter for FLT3-ITD+ pts (P < .001) | Yes‖ | De novo and secondary | 192 (67/125) | 16-60 (47) | 34 mo¶ | Higher WBC, higher LDH, higher percentage of PB and BM blasts | Fröhling et al 43 |
| CRD: significantly shorter for FLT3-ITD+ pts (P = .007) | Yes‖ | 142 (47/95) | |||||
| CR rate: no significant difference | — | De novo and secondary | 84 (33/51) | 18-60 (NR) | NR | NR | Beran et al45 |
| OS: significantly shorter for FLT3-ITD+ pts (median, 32 vs 108 wk; P < .001) | ND | 84 (33/51) | |||||
| CRD: significantly shorter for FLT3-ITD+ pts (median, 42 vs 75 wk; P = .04) | ND | 58 (17/41) | |||||
| CR rate: no significant difference | — | De novo and secondary | 84 (20/64) | 61-82 (NR) | NR | NR | Beran et al45 |
| OS: no significant difference (median, 14 vs 34 wk) | — | 84 (20/64) | |||||
| CRD: no significant difference (median, 20 vs 45 wk) | — | 39 (11/28) | |||||
| FLT3ITD/− versus FLT3-ITD− | |||||||
| CR rate: no significant difference (75% vs 86%) | — | De novo | 67 (8/59) | 20-59 (37/45)# | 1.7 y | Higher WBC | Whitman et al18 |
| OS: significantly shorter for FLT3ITD/− pts (median, 7 vs 46 mo; P = .001) | Yes | 67 (8/59) | |||||
| DFS: significantly shorter for FLT3ITD/− pts (median, 4 vs 52 mo; P = .001) | Yes | 57 (6/51) | |||||
| FLT3-ITD+ versus FLT3-Asp835+ versus FLT3-WT | |||||||
| CR rate: no significant difference (65% vs 82% vs 76%) | — | De novo and secondary | 220 (67/28/125)** | 16-60 (47) | 34 mo | Secondary AML less Common in FLT3-ITD+ and FLT3-Asp835+ pts | Fröhling et al43 |
| FLT3-ITD+ versus FLT3-Asp835+ | |||||||
| OS: no significant difference | — | De novo and secondary | 95 (67/28) | 16-60 (47) | 34 mo¶ | Higher LDH, higher percentage of PB blasts | Fröhling et al43 |
| CRD: no significant difference | — | 70 (47/23) | |||||
| FLT3-Asp835+ versus FLT3-WT | |||||||
| OS: no significant difference | — | De novo and secondary | 153 (28/125) | 16-60 (47) | 34 mo¶ | Higher percentage of BM blasts | Fröhling et al43 |
| CRD: no significant difference | — | 118 (23/95) |
Only studies comprising 50 or more patients are included. A smaller study on 34 patients receiving high-dose chemotherapy and ASCT in first CR was also published.55 pts indicates patients; MVA, multivariable analysis; FLT3-ITD+, patients with FLT3-ITD; FLT3-ITD−, patients without FLT3-ITD; CR, complete remission; OS, overall survival; DFS, disease-free survival; EFS, event-free survival; FLT3-WT, patients with FLT3 wild-type; CRD, CR duration; —, no significant difference in univariable analysis (MVA not performed); ND, not done; NR, not reported; WBC, white blood cell count; LDH, serum lactate dehydrogenase level; FLT3-Asp835−, patients without activating point mutations in codon 835 within the activation loop in the tyrosine kinase domain of the FLT3 gene; PB, blood; BM, bone marrow; FLT3ITD/−, patients with the FLT3-ITD lacking an FLT3-wild-type allele; FLT3-Asp835+, patients with FLT3-Asp835 mutations.
Numbers of patients for whom clinical data were available.
FLT3-WT (ie, FLT3-ITD− and FLT3-Asp835−).
Median age of patients with FLT3-ITD/patients without FLT3-ITD.
Mean age.
In this analysis, patients with FLT3-ITD, FLT3-Asp835 mutation, or both were combined into I group (FLT3 mutation) and compared with patients without FLT3-ITD and/or FLT3-Asp835 mutation.
Follow-up reported for all 220 patients studied.
Median age of patients with FLT3ITD/−/patients with FLT3WT/WT.
Number of patients with FLT3-ITD/patients with FLT3-Asp835/patients with FLT3-WT.