Consolidation of AML Therapy with Autograft and Allograft Procedures Does not Negate the Poor Prognostic Impact of FLT-3 Internal Tandem Duplications: Results for UK MRC AML 10 and 12 Trials.
Reviewer: Julie Draznin Maltzman, MD
Last Modified: December 9, 2002
Presenter: Panagiotis D. Kottaridis Presenter's Affiliation: London, UK Type of Session: Scientific
Currently >80% of AML pts over the age of 60 will attian a complete remission (CR).
Those who receive post CR intensification therapy (either with high dose chemotherapy or bone marrow transplant) will have a better overall survival.
A significan number of pts will still relapse.
It is often helpful to look for markers that will predict which pt will relapse and which will not.
By identifying these high risk patients it is conceivable that more intensive upfront therapy maybe beneficial for this subpopulation.
Earlier studies by this group showed that a mutation in the FLT-3 gene confers a poor prognosis.
There are three types of mutations known to occur in the FLT-3 gene, the one that confers a poor prognosis is one where there are multiple duplications of the DNA encoding for this gene. This is called Internal tandem duplications or internal tandem repeats.
These investigators are studying the possible intensification of induction therapy in this group of FLT-3 positive patients and their resultant outcomes.
Materials and Methods
293 pts in first complete remission were taken from 2 large British AML trials.
138 men and 155 women aged 15-59 were enrolled.
All pts were given intensive induction and consolidation therapy. After achieving CR they were either taken for an allo transplant, auto transplant, or no further therapy was given. These decisions were made based upon matched sib availability, pt preference, and physicain discretion.
Of the pts who had an allo transplant 19% had the FLT-3 internal tandem duplication mutation; and 26% of the auto transplant pts had this mutation.
The disease free survival (DFS) in the auto transplant groups was 57% for FLT-3 negative pts and 43% for FLT-3 mutation carriers.
The relapse rate for the auto transplant group was 32% for the FLT negative pts and 51% for the FLT-3 mutation carriers.
DFS for the allo transplanted pts was 56% for the FLT-3 negative pts and 33% for the FLT-3 positive carriers.
Relapse was 21% for the FLT-3 carriers and 19% for the FLT-3 negative pts in the allo group. However,the authors caution that a statistical difference can not be inferred because of many treatment related deaths in the allo group.
Non relapse related mortality in the allo group was indeed high and was significantly higher for the FLT-3 group -- 60% as opposed to 29% for the FLT-3 negative group. This was an unexpected and unexplained finding by the investigators.
When comparing both the allo and auto groups side by side, the FLT-3 positive pts had an overall survival of 43% for the allo group and 58% for the auto group. The FLT-3 negative pts undergoing an allo had a 63% overall survival and the same pts undergoing an auto transplant had a 66% overall survival.
This study shows no evidence that the use of allo transplant for AML improves survival for FLT-3 mutation carriers vs non carriers.
FLT-3 should therefore not be used as a criteria for deciding for or against allo transplant in these pts in first CR outside of a clinical trial.
Further studies are needed to help physicians identify the subgroup of pts who will benefit from upfront more intensive therapy. The presence or absence of the FLT-3 mutation is not one of those deciding factors.
Although FLT-3 confers a poor prognosis to adult AML, more intensive upfront therapy for these pts is not the answer.
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