Thread by @haematognomist

🧵Our latest in @BloodJournal
@coleman_lindsley @c_j_gibson @DanaFarberNews

Older patients with AML undergoing HCT have high rates of relapse & non-relapse mortality

We investigated how outcomes relate to both baseline characteristics and molecular MRD

tinyurl.com/4bn76ham

2. @DrChrisHourigan and others have shown that AML pts with mutations at remission (molecular MRD) have more relapse➡️ inferior survival after HCT, especially if receiving reduced intensity conditioning.
tinyurl.com/23rrbjte

3. We wondered:

1⃣ Is prognostic impact of MRD the same for patients age ≥ 60 (underrepresented in RCTs)?

2⃣ Is mutation persistence related to features present at diagnosis?

4. In 295 pts age ≥ 60 undergoing HCT in CR1, we combined baseline AML genetics and clinical variables to stratify into 4 groups with distinct risk post HCT:

5. 192 of these pts had a CR1 sample. Comparing to dx allowed us to know which mutations were new vs old.

Mutations present at AML dx persisted in 80% of pts assessed.

In a minority, persistent mutations were only in DNMT3A or TET2, but most had at least one other (“MRD+”).

6. Likelihood of being MRD+ was associated with:

▪️ Secondary-type genetics (as defined here tinyurl.com/3humfzfx)

▪️ TP53 mutations

▪️ Poor risk cytogenetics

Makes sense - all of these features are associated with therapeutic resistance.

7. In univariable analysis, MRD+ patients had inferior survival.

But...

After considering baseline risk, there was no difference between MRD+ and MRD- patients’ survival.

8. How do we square this with 09-01 findings referenced above? Two thoughts:

First - maybe MRD+ has different impact in our pts than younger RCT-eligible population in 09-01.

Older pts: MRD+ often reflects underlying MDS?

Younger pts: MRD+ more often reflects persistent AML?

9. Second – perhaps for many, MRD+ is a reflection of disease-intrinsic risk, encoded by genetic features:

Chemoresistant AML is more likely to persist after induction

But when comparing to pts with similar baseline risk, MRD+ doesn’t confer additional prognostic information.

10. MRD in AML is complicated & large prospective studies like MEASURE @CIBMTR clinicaltrials.gov/ct2/show/NCT05… & academia-industry-@US_FDA partnerships through @FNIH_Org biomarkers consortium will help bring rational MRD approaches forward into clinical practice

tinyurl.com/2p8mrwcs

11. Many thanks to our collaborators across 6 transplant centers, including @pankitvachhani
@bryanhambley1 @DrMiguelPerales @EuniceWangMD
@LukaszPGondek @DrStevenDevine and others not on twitter!

+ Funding from @ASH_hematology

12. Lastly, this project has spanned medical school and residency. Could not have completed this project successfully without the incredible mentorship from @ColemanLindsley and @c_j_gibson in addition to the @DanaFarberNews Bone Marrow Transplant team.

#leusm #bmtsm #MedTwitter