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Internal tandem duplication (ITD) of the juxtamembrane domain of the FMS-like tyrosine kinase-3 (FLT3/ITD) gene is a common mutation detected in 30% of patients with acute myeloid leukemia (AML) and is associated with poor survival outcomes and high relapse rates. However, a recent study has shown that these negative effects are only seen if the ratio of mutated to normal alleles is > 0.5, which adds to the controversy of the role of allogenic-stem cell transplantation (allo-SCT) in FLT3-mutated patients in their first complete remission (CR1).1
In a retrospective study, Grzegorz Helbig and colleagues from the Medical University of Silesia, Katowice, Poland, aimed to evaluate the potential factors that may have an impact on the outcome of FLT3-mutated patients after allo-SCT.1
Table 1. Patient characteristics1
FLT3/ITD, FMS-like tyrosine kinase-3/internal tandem duplication; MDS, myelodysplastic syndrome |
|
Variable |
Total patients (N = 43)
|
---|---|
Gender, female/male % |
65.1/34.9 |
Median age, years (range) |
45 (19–67) |
Karyotype, % |
|
Diploid |
60 |
+ 8 |
9 |
− 5q |
2 |
+ 11 |
2 |
inv9 |
2 |
− 7q |
2 |
t(1;7) |
2 |
+ 3,+ 13 |
2 |
no metaphases |
19 |
Prior MDS, % |
7 |
Hematologic response at transplant, % |
|
First or second complete remission |
79 |
Marrow aplasia |
21 |
FLT3/ITD mutation at transplant, % |
|
Negative |
63 |
Positive |
27 |
Median time from diagnosis to transplant, months (range) |
16.7 (5.1–76.0) |
Table 2. Univariate and multivariate analysis of risk factors for OS and LFS1
CI, confidence interval; FLT3/ITD, FMS-like tyrosine kinase-3/internal tandem duplication; HR, hazard ratio; LFS, leukemia-free survival; OS, overall survival |
|||||
Outcome |
Risk factor |
Univariate analysis (log rank) |
Multivariate analysis (Cox regression) |
||
---|---|---|---|---|---|
Survival at 2 years (%) |
p value |
HR (95% CI) |
p value |
||
OS |
Type of donor |
|
|
|
|
|
Related |
19 |
0.010 |
0.35 (0.12–1.0) |
0.050 |
|
Unrelated |
68 |
|
|
|
|
FLT3/ITD status at transplant |
|
|
|
|
|
Negative |
74 |
0.001 |
2.67 (0.94–7.56) |
0.060 |
|
Positive |
21 |
|
|
|
LFS |
Type of donor |
|
|
|
|
|
Related |
67 |
0.020 |
— |
|
|
Unrelated |
28 |
|
|
|
|
FLT3/ITD status at transplant |
|
|
|
|
|
Negative |
74 |
0.001 |
5.3 (1.97–14.2) |
< 0.001 |
|
Positive |
25 |
|
|
|
The strong positive correlation between FLT3 MRD positivity and MRD-FC positivity suggests that pretransplant detection of the FLT3/ITD mutation by PCR may serve as a reliable MRD marker and predict posttransplant outcome, particularly LFS, better than hematological disease status.
The authors note that although the study was limited by the small sample size, the results are in-line with other published studies. However, they suggest that further studies with larger numbers of patients are needed to draw final conclusions.
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