Aaron Logan, MD, PhD, MPhil

#tandem26 Ferrara: JAKi facilitates tissue repair whereas steroids actually inhibit it (even though, yes, they do inhibit alloimmune responses). Ferrara’s goal is to move steroids to 2nd line tx for GVHD!

#tandem26 Ferrara: thus far, most GVHD pox/treatment has focused on the intimation and persistence of the alloimmune response, but efforts to improve tissue resistance to damage are important. Eg, intestinal stem cells are damaged by GVHD cytokines. Rux prevents ISC apoptosis, but steroids don’t.

#tandem26 Ferrara: refinement of biomarker + clinical sx based aGVHD stratification (MAGIC composite) now gives greater clarity in predicting outcomes at onset of aGVHD.

#tandem26 Ferrara: beautiful and touching start to his E Don Thomas lecture by dedicating the talk to John Galvin, who we shockingly lost this past year at far, far too young an age.

#tandem26 Unfortunately, I could only make the end of Stella Davies’s Bortin Lecture, but absolute respect to her for using her platform to speak out against the anti-immigrant, anti-democratic trajectory of our current course in America! “We can not sit this one out.” Agree 1000000% !!!

#tandem26 #bmtsm Rafati: in triple neg MF, TET2mut assoc with incr relapse and inferior OS, whereas TET2mut doesn’t affect outcomes with MF with canonical driver mutation.

#tandem26 #bmtsm Rafati: triple neg MF have inferior alloHCT outcomes. Overall conventional high risk gene must not assoc w survival, but TP53m assoc w inferior outcome with any driver mutation.

#tandem26 #bmtsm Rafati: driver mut found in 81.7%. 18% were triple neg. 94% found to have at least one somatic mut, 1/3 with ASXL1.

#tandem26 #bmtsm Rafati: @cibmtr.bsky.social analysis of genetic predictors of alloHCT outcomes in myelofibrosis. Known high risk assoc w ASXL1+nonCALR/MPL muts. N=930 evaluated here w 95 gene assay.

#tandem26 #bmtsm Popat: age and IPSS not correl w outcomes. TP53 mut status was assoc w 3yr PFS/OS 64% with TP53wt vs 50% with TP53m. Relapse >3x higher in TP53m. Impressive outcomes, but the high NRM is problematic, esp for TP53wt — ie at 12mos, only 6% relapse but OS 69% due to the high toxicity.

#tandem26 #bmtsm Popat: N=50 w HR-MDS underwent CLADILLAC allo. Median age 63, 84% matched donors, 94% PBSC. 28% with TP53 abnormalities. 3yr PFS/OS both 60%, relapse 10%, NRM 30%.

#tandem26 #bmtsm Popat: updated outcomes on CLADILLAC conditioning for MAC allo in HR-MDS. ~1/3 cured with current standard approaches. Age 18-70 eligible for this trial. N=50.

#tandem26 #bmtsm Gyurkocza: low precond BTNL3 expression was associated with poor outcomes in those who recd TBI.

#tandem26 #bmtsm Gyurkocza: several genes associated with outcomes when expressed highly precond, especially CCDC144A. At day 0, CD34 and CACNA1 expression assoc with PFS/OS.

#tandem26 #bmtsm Gyurkocza: FluTreo with TBI N=17 vs 14 wo TBI. Bulk marrow RNAseq used with ML assisted analyses.

#tandem26 #bmtsm Gyurkocza: differential gene expression during conditioning correlate with outcomes in AML/MDS. Marrow collected pre cond and at day 0 after FluTreo +/- TBI200. N=30 evaluable.

#tandem26 #bmtsm Duarte: MDS/MPN N=94 vs MDS N=476. Median older age in MDS/MPN and lower KPS. OS and RFS lower in MDS/MPN, with slightly higher (not significant) NRM.

#tandem26 #bmtsm Duarte: allo outcomes in MDS/MPN syndromes (CMML et al) vs other MDS, a Brazilian analysis. N=570 across 33 centers.

#tandem26 #bmtsm Kongtim: although better survival outcomes with FM regimens, they were associated with higher early TRM.

#tandem26 #bmtsm Kongtim: FM regimens (100/140) outperform other Flu based conditioning wrt DFS/CIR/OS.

#tandem26 #bmtsm Kongtim: @cibmtr.bsky.social analysis of Flu/Mel vs other RIC in pts age 50+ with AML/MDS relapse, total N=11,731 from 183 centers. ~94% PBSC

#tandem26 #bmtsm Reshef: AlloHeme also outperformed standard bone marrow analyses for MRD, meaning this approach can decrease dependence on marrows since AlloHeme is performed on PB.

#tandem26 #bmtsm Reshef: AlloHeme has good test performance characteristics, including 95% NPV and ROC AUC 0.89. Lead time between AlloHeme+ and clinical relapse was median 41days (not diff between AML and MDS, interestingly). AlloHeme outperforms standard chimerism.

#tandem26 #bmtsm Reshef: AlloHeme evaluable were N=198. At 2, 3, and 6mos post-also AlloHeme positivity highly associated with relapse.

#tandem26 #bmtsm Reshef: AlloHeme, a PB test to predict post-transplant AML/MDS relapse, does not require prior leukemia marker ID. N=285 in ACROBAT study to evaluate this test.

#tandem26 #bmtsm Dvorak: higher exposure to ATG decr GVHD risk but may abrogate GVL and expose to incr infections. Really should incorporate absolute T cell count and timing of administration into ATG dosing to personalize.

#tandem26 #bmtsm Dvorak: ATG effect influenced by number T cells present in the host (and that ratio is not generally manipulated other than TCD).

#tandem26 #bmtsm Dvorak: increased exposure to TBI, Busulfan, and Melphalan all associated with incr GVHD risk.

#tandem26 #bmtsm Dvorak: conditioning regimen toxicity known to have strong correlation with development of GVHD

#tandem26 #bmtsm Dvorak: optimal HSPC dose unknown, but infused CD3 dose does not affect GVHD outcomes with a/b TCD, but CD34 dose does influence GVHD risk (surrogate for more APC transfer?).