🚨 Spectrum, prevalence, and clinical correlates of PPM1D mutations in patients with clonal hematopoiesis and clonal cytopenias. I am very pleased with this collaborative effort. Grateful to @MrinalPatnaik for his mentorship. Paper highlights 👇🏽 🧬 PPM1D mutations in clonal hematopoiesis – what really happens after chemo? Multi center study of 337 CH/CCUS patients dissects how #PPM1D and #TP53 mutations shape therapy-related clonal hematopoiesis. 👇 1️⃣ PPM1D is the signature of therapy-related CH •50% had PPM1D-mut/TP53-WT •7% had PPM1D-mut/TP53-mut •These genotypes were highly enriched in therapy-related CH/CCUS (up to 80% of cases). 2️⃣ All PPM1D mutations were truncating exon-6 variants Median VAF only 6% — small clones, but biologically meaningful. 3️⃣ Latency after genotoxic therapy was strikingly short Median time from last chemo/radiation to detection: •PPM1D-mut groups: ~6 months •TP53-mut only: ~11 months •WT/WT: ~24 months → PPM1D clones emerge fast after DNA-damaging therapy. 4️⃣ Strong link with PARP inhibitors & radioligand therapy In therapy-related CH/CCUS: •PARPi exposure: 24–26% in PPM1D-mut vs 0–3% in WT groups •Radioligand therapy: ~25–26% in PPM1D-mut vs near-zero otherwise. 5️⃣ Despite this… PPM1D clones rarely progressed Rates of transformation to MDS/CMML: •PPM1D-mut/TP53-WT: 2% •PPM1D-mut/TP53-mut: 4% •TP53-mut only: 18% •WT/WT: 12% AML transformation occurred only in WT/WT group. 6️⃣ When both PPM1D & TP53 are present, neither always “wins” Among co-mutated patients: •~⅓ #PPM1D-dominant •~⅓ #TP53-dominant •~⅓ co-dominant Therapy-related CH showed more co-dominant competing clones, suggesting chemo creates a “Darwinian battlefield”. 7️⃣ The size of the PPM1D clone matters Using ROC-derived cut-off: •PPM1D VAF ≥13% → independently predicts worse PFS & OS (HR ~2.3 for both). Multiple PPM1D mutations ≠ worse outcome — it’s the clone size, not count. 8️⃣ Clinical message #PPM1D mutations are: •Common after chemo/PARPi/radioligand therapy •Often small, fast-emerging clones •Surprisingly low risk for malignant transformation, even with TP53 — unless the VAF climbs ≥13%. Take-home: PPM1D-mut CH appears to be a therapy-selected, early-emerging, usually indolent precursor state — but rising clone size may signal real danger. doi.org/10.1182/bloodadvance…

Transplant in the modern-ish era for AdvSM. 1 yr PFS of 74% in the SM-AHN group but only 59% overall. Unclear yet if KIT inhibitors peri-transplant will help improve these outcomes. British Journal of Haematology | Wiley Online Library onlinelibrary.wiley.com/doi/…

hoparx.org/about-us/hopa-pub… Podcast✌️out now! check it out on Spotify or Apple Podcasts now

🚨 Latest paper from #COMMAND_consortium, reporting heterogeneity in clinical outcomes in #TP53m MPN, one of largest cohort of TP53m MPN: 1. Multihit TP53 had inferior outcome in chronic phase MPN, not so in MPN-AP or BP. Similar to our reports in HR-MDS/AML. 2. MH TP53 commonly seen in MF or MPN-AP/BP. Rare in PV/ET. 3. Allo-HCT improves outcome, less so with MH TP53/complex CG. 4. TP53 with low VAF commonly seen in PV/ET and does not impact disease progression significantly. @Dr_RoryShallis @Irumkhan_hem @ChenyuLinMD @AlexColtoff @Anand_88_Patel @Wang_Yu_Hung et al. @MPN_Hub British Journal of Haematology | Wiley Online Library onlinelibrary.wiley.com/doi/…

📢 @HOPArx members: one more day to submit your votes to select the next BIG idea‼️Official Votes here: hopa.execinc.com/edibo/2025B… Use this poll to see the ✨unofficial✨ spoilers of our colleagues votes🧐

Review of fedratinib with John Mascarenhas. First Downey Jr, then McConaughey - is fedratinib going to have a career renaissance as well? ashpublications.org/bloodadv…

Be sure to check out the great work led by @GeorgioMedawar tonight on extended vs standard HMA dosing with VEN for ND AML! ash.confex.com/ash/2024/webp…

Thrilled to be presenting at @ASH_hematology #ASH2024, our abstract on extended vs. standard duration HMA+Ven in ND-AML! Always grateful to be working with Dr. @AlexColtoff and our collaborators from @TGHCares @USouthFlorida and @MountSinaiNYC ash.confex.com/ash/2024/webp…

LGM

Grateful to have presented our experience with Pacritinib and Momelotinib after Ruxolitinib failure in patients with Myelofibrosis @SocietyofHemOnc #SOHO2024 We observed trends toward ⬆️ Hgb, ⬆️ PLT, and ⬇️ in transfusion dependency within 3 months of use #mpnsm #HemOnc

When will the candidates address the real issues?

So grateful for our amazing #MPNworkshopNC co-chairs for helping us put together an incredible meeting in amazing #AshevilleNC @doctorpemm @LindsayReinMD @BrandiReeves1 @AlexColtoff #RupaliBhave #MikeGrunwald @LevineCancer @WakeCancer @DukeCancer @UNC_Lineberger @muschollings @MDAndersonNews

👉👉👉Delighted to invite you to join us #MPNCarolinas24 ➡️ Aug 23-35,2024 #Asheville NC for our first annual MPN Workshop of The Carolinas 2024 ➡️ a re-boot of our #TXMPNWorkshop series! 🙌 Chairs: @mpdrc & @doctorpemm | #MPNSM | @VJHemOnc 👏 southpiedmontahec.org/event/…

In the latest episode of “PV Pod: Stories from the Marrow,” Dr. Douglas Tremblay from Mount Sinai School of Medicine discusses #PolycythemiaVera (PV) progression and the challenges in predicting and preventing this #RareDisease. Listen to PV Pod here: pod.link/1683012869

onlinelibrary.wiley.com/doi/… More data regarding clinical and prognostic utility of D14 marrows. Most interesting to me was 63% of pts with RD at D14 had CR at count recovery. Personally, I almost never re-induce on D14 for good-risk and even hesitate for most intermediate-risk.

onlinelibrary.wiley.com/doi/… - 84 AML pts stopped VEN (55%) or HMA+VEN (45%) - Median f/u 23 mos, only pts off tx for 3+ mos included - mOS 44 mos, mTFS 16 mos (whole cohort) - mOS 19 mos, mTFS 10 mos (R/R) - NPM1 MRD- (only 7 pts) 2-year OS 100% - Very selected pop, but encouraging

onlinelibrary.wiley.com/doi/… ARES - ET randomized 1:1 asa qd vs bid - Decrease in TXB2 with bid - no difference in thrombosis (to be expected with 20 mo f/u) - Some symptoms better w/bid, but open-label and all pts on asa at start (role for step-wise asa escalation for sx control?)

#EHA2024 #EHA24 #poster_session #TP53m #MPN #mpnsm Genomic landscape, impact allelic burden, time to progression from CP-AP/BP in TP53m MPN—> AML TP53m with VAF>40 had poorer outcome. No significant impact of type of induction on outcome. Special thanks to #COMMAND_consortium @MobasherK @Anand_88_Patel @Dr_RoryShallis #Jan_Bewersdorf #Ehab_Atallah #Aron_Goldberg #Kashish_Shah #Alex_Coltoff

Landmark Paper: the study published in 1998 by Bloomfield et al. established the standard for consolidation therapy in acute myeloid leukemia patients with core binding factor abnormalities. haematologica.org/article/vi…