Manoj Raghavan

Good luck Laura@ London Paris Ride : Make a donation today to support London Paris Ride ride.myeloma.org.uk/laura-conway #london-paris-ride via @raisely @MyelomaUK @CCH_Bham @

From today, all UK clinical trials must be registered and results reported by law. Sponsors must: • Register trials publicly • Report results within 12 months • Share summaries with participants A major step for transparency, accountability, and better medicine. #AllTrials

Glad to share our @Yale tour-de-force review of #MDSsm published in @Nature Reviews of Clinical Oncology (Free online read at rdcu.be/fdl9e) which has to be the most comprehensive review we have ever written on the subject covering all relevant areas from epidemiology, pathogenesis, diagnosis, risk stratification, to current and evolving therapies for lower and higher risk disease @YaleCancer @YaleHematology @YaleMed

Our newest paper on association between early neutropenia and thrombocytopenia with subsequent clinical response to imetelstat in lower risk #MDSsm nature.com/articles/s4140…

Time for a check-up! During their 10-day mission, the Artemis II crew will verify the AVATAR organ chips are working properly as they gather data on how deep space radiation and microgravity affect bone marrow cells. go.nasa.gov/3Ok9hVO

👉 New paper from @TheEBMT practice harmonisation and guidelines committee: practical approaches to defining remission and relapse after allo-HCT in MDS/MPN overlap syndromes — a pragmatic approach to these challenging 🩸 disorders! @TheEBMT_Trainee @CArmstrongHaem #MDSsm #MPNsm gbr01.safelinks.protection.outlook.com/?url=https%3A%…

It appears that IDH2 mutations within setting of clonal hematopoiesis are expanded with exposure to lenalidomide. The authors surmise that this may be due to Ikaros downregulation. So the question is: do we really expect second heme cancer incidence to be lower with Pom or CELMoDs? Manuscript here: ashpublications.org/blood/article/…

🧬 50 Pearls — NPM1-Mutated AML & Co-Mutational Risk (HARMONY Study) (Based on the Leukemia 2026 HARMONY analysis) 1️⃣ NPM1 mutation occurs in ~30% of adult AML and defines the largest AML molecular subtype. 2️⃣ Prognosis is generally favorable but strongly influenced by co-mutations. 3️⃣ Historically, FLT3-ITD was the only co-mutation included in risk stratification. 4️⃣ The ELN-2022 system classifies NPM1-mut AML mainly by FLT3-ITD presence. 5️⃣ The HARMONY database analyzed 1,763 intensively treated adult NPM1-mut AML patients. 6️⃣ The training cohort included 1001 patients from AMLSG and HOVON trials. 7️⃣ Median age was ~53 years. 8️⃣ Normal karyotype occurs in ~80–88% of NPM1-mut AML. 9️⃣ Composite CR rate ~87% after induction. 🔟 Allo-HSCT performed in ~34% of patients. ⸻ 🔬 Co-Mutation Landscape 1️⃣1️⃣ Most frequent mutations: FLT3 (54%), DNMT3A (53%). 1️⃣2️⃣ Other frequent genes: NRAS, PTPN11, TET2, IDH1/2. 1️⃣3️⃣ FLT3-ITD present in ~39% of cases. 1️⃣4️⃣ DNMT3A mutations often co-occur with FLT3-ITD. 1️⃣5️⃣ 59.5% of FLT3-ITD cases also carry DNMT3A mutations. 1️⃣6️⃣ Triple mutation NPM1 + FLT3-ITD + DNMT3A is common (~23%). 1️⃣7️⃣ This triple-mutated group has very poor prognosis. 1️⃣8️⃣ Median RFS in triple mutation AML <9 months. 1️⃣9️⃣ IDH mutations may modulate prognosis depending on context. 2️⃣0️⃣ IDH mutations may paradoxically improve outcomes in some FLT3-ITD subsets. ⸻ 🧬 Clonal Evolution 2️⃣1️⃣ Early mutations: DNMT3A, TET2, IDH1/2. 2️⃣2️⃣ NPM1 mutations occur later in leukemogenesis. 2️⃣3️⃣ RAS pathway mutations tend to occur late in disease evolution. 2️⃣4️⃣ Early epigenetic mutations may create a pre-leukemic stem cell state. 2️⃣5️⃣ NPM1-mut AML may contain up to 13 gene mutations per patient. ⸻ 🧪 HARMONY Risk Classification 2️⃣6️⃣ The model integrates FLT3-ITD, DNMT3A, IDH1/2, TET2. 2️⃣7️⃣ Patients stratified into 3 risk groups. 2️⃣8️⃣ Favorable: 51.8% of patients. 2️⃣9️⃣ Intermediate: 24.8%. 3️⃣0️⃣ Adverse: 23.4%. 3️⃣1️⃣ Median OS favorable group ~14.4 years. 3️⃣2️⃣ Median OS intermediate group ~2.2 years. 3️⃣3️⃣ Median OS adverse group ~0.9 years. 3️⃣4️⃣ CR rate highest in favorable group (~91%). 3️⃣5️⃣ RFS not reached in favorable subgroup. ⸻ 🔄 Impact vs ELN Classification 3️⃣6️⃣ The HARMONY model reclassified ~42.7% of NPM1-mut AML patients. 3️⃣7️⃣ Many ELN favorable cases shifted to intermediate risk. 3️⃣8️⃣ Some intermediate patients moved to adverse category. 3️⃣9️⃣ Predictive accuracy improved vs ELN-2022 (AUC 0.695 vs 0.635). 4️⃣0️⃣ Demonstrates importance of co-mutational patterns. ⸻ 🩺 Transplant Implications 4️⃣1️⃣ Allo-HSCT in CR1 benefits most the adverse subgroup. 4️⃣2️⃣ Limited benefit of HSCT in favorable subgroup. 4️⃣3️⃣ Intermediate group shows moderate transplant benefit. 4️⃣4️⃣ HSCT hazard ratio improvement strongest in adverse group. ⸻ 🧪 Other Genomic Insights 4️⃣5️⃣ TP53 mutations remain rare but highly adverse. 4️⃣6️⃣ RUNX1 mutations associated with worse outcomes. 4️⃣7️⃣ SRSF2 mutations show intermediate prognosis. 4️⃣8️⃣ STAG2 mutations may correlate with favorable outcomes. 4️⃣9️⃣ Adverse cytogenetics are uncommon in NPM1-mut AML. 5️⃣0️⃣ Combining baseline genomics + MRD will likely define future AML risk models. ⸻ 🧬 Take-Home: NPM1-mut AML prognosis is not uniform — co-mutational architecture (FLT3-ITD, DNMT3A, IDH, TET2) significantly refines risk and may guide allo-HSCT decisions. ⸻ #AML #NPM1 #Hematology #Leukemia #PrecisionMedicine #MyeloidNeoplasms #HemOnc #ASH #ELN2022 #MolecularHematology

My X feed sends me stupid cat videos and Cancer/ leukaemia genomics posts. How to combine the two. Phase 1 trials in cats? (They won't let you stroke them if they don't want you to...) science.org/doi/10.1126/sc…

VEXAS syndrome is a newly discovered multisystemic disease affecting most organs. A new Review provides a comprehensive overview of VEXAS syndrome, including the disease's discovery, diagnosis, and treatment: spkl.io/6014AsjYw

People with TP53 mutations have blood stem cell clones (CHIP) which promote chronic inflammation, aging, and risk of blood cancers. This can be blocked by multiple means (as shown below) to potentially prevent cancer, but CHIP is not assayed in the clinic. jci.org/articles/view/… @jclinicalinvest

Tge value of donating marrow and cord stem cells #leusm @NHSBT: 'Small vial of blood saved my life after cancer diagnosis' - BBC News bbc.co.uk/news/articles/…

2025 Update on MRD in Acute Myeloid Leukemia: A Consensus Document from the ELN-DAVID MRD Working Party ashpublications.org/blood/article/…

#ASH25 Largest cohort to date of de novo BCR::ABL1⁺ AML. Entity shows strong association with adverse cytogenetic and molecular abnormalities. Adding a BCR::ABL TKI to intensive chemotherapy significantly improves outcomes: •CR/CRi: 90% vs 67%. •5-year OS: 63% vs 39%. •TKI + intensive chemo should be standard of care for eligible patients. Two-thirds of patients treated with TKI + intensive chemo without allo-HSCT did not relapse. Future ELN classification should no longer categorize de novo BCR::ABL1⁺ AML as adverse.

PRISM Score is the new “IPSS-M” risk stratification & prognostication of newly Dx AML Tx with HMA/Ven. Fantastic presentation by @CLachowiez & privilege to be part of this analysis @UNC_Lineberger . You can calculate score at prism-aml.com @ASH_hematology #ASH2025

We're proud to share the results from the AMMO trial presented at #ASH2025 by Dr Daniel Wiseman. ASTX727 treatment resulted in the first survival benefit in over 30 years for patients with advanced MDS/MPN overlap syndromes vs current standard of care.

Proud to have challenged the dogma and offer Aza Ven to young patients with AML who face higher risks of complications with 7+3 in LMIC settings! No better moment to plug our study our now in @BloodPortfolio #ASH25 😉 tinyurl.com/bddh8czz

I am definitely not an iron specialist…but wow, this study is pure metal! Impressive safety, better survival, fewer transfusions: science never stops surprising us. Always amazed by what rigorous research can reveal. #ASH25 #ASHScavengerHunt ⁦@ASH_hematology⁩ ⁦@TheIACH

After 50+ year of reigning the AML throne, 7+3 is officially toppled by Dr. Amir Fathi and the PARADIGM investigators at the #ASH25 plenary on 12/7/2025 Huge paradigm shift for the AML filed and a pleasure to see one of our own shine on the stage ✨

Wow!! 🔥🔥 CDK4/6 inhibition prevents selection of #ClonalHematopoiesis with DNA-damage repair mutations after chemotherapy! Awesome presentation from Irenaeus Chan from @KellyLBolton lab! #ASH25