Jonas Moreno P

🚨 AML is NOT one disease — it’s a spectrum. Risk stratification drives EVERYTHING: 🔬 Prognosis 💊 Treatment choice 🧬 Transplant decisions From ELN 2022 risk groups → to 7+3, targeted therapy & HSCT, mastering this algorithm is key for every oncologist. 💡 Key takeaways: ✔️ Cytogenetics = backbone ✔️ Favorable → chemo ✔️ Adverse → transplant ✔️ Venetoclax + HMA = game changer ✔️ APL = oncologic emergency 📌 Save this for revision. Teach it. Use it. — Dr Rupam Manna #AML #Leukemia #Hematology #MedicalOncology #Oncology #CancerEducation #ELN2022 #MRD #HSCT #Venetoclax #MedEd #FOAMed

Many of us misunderstand KMT2A leukemia. FDA says “translocation”—biology says fusion. FISH ≠ partner. DNA panels miss it. Only KMT2Ar responds. Break-apart tells you that. RNA tells you what. Biology tells you if it matters.

hematomorph.com💞

POD24 = a clinical inflection point. Across diseases: • Follicular lymphoma • Waldenström macroglobulinemia • Mantle cell lymphoma • Marginal zone lymphoma • Peripheral T-cell lymphoma • Multiple myeloma Different labels. Same signal: 👉 Early progression = aggressive biology 🧬 TP53 🧬 Genomic complexity 🧬 Clonal evolution 🧬 Immune escape If it breaks within 24 months, it was never indolent. #lymphoma #myeloma #hemetwitter #CART

🧬 Tisagenlecleucel in R/R Follicular Lymphoma — 5-Year ELARA Update (50 Pearls) 📊 Presented by Dr Mostafa Saleh — KFSHRC ⸻ 👥 Study design 📊 Phase II | n=97 | ≥2 prior lines 📅 Median follow-up ≈ 61 months ⸻ ⚠️ High-risk population 📊 FLIPI ≥3 ≈ 60% 📊 POD24 ≈ 62% 📊 Bulky ≈ 64% 📊 Double refractory ≈ 68% ⸻ 📈 Efficacy 🎯 ORR ≈ 86.2% 🏆 CR ≈ 68.1% ⏳ Median DOR → Not reached ⸻ 📊 PFS 📈 Median PFS ≈ 53.2 months ⸻ 🧬 Long-term outcomes 📊 5-year PFS 🟢 Overall ≈ 46% 🏆 CR pts ≈ ~60% ⸻ 📈 Overall survival 🟢 5-year OS ≈ 74.1% 🧠 Durable benefit even in high-risk groups ⸻ 🔥 High-risk subgroup outcomes (5-year PFS) ⚠️ FLIPI high → ~35.5% ⚠️ POD24 → ~41.1% ⚠️ Bulky → ~45.1% ⚠️ Double refractory → ~50.5% ⸻ 🧠 Key insight 🔥 Sustained efficacy despite adverse biology ⸻ 🛡️ Long-term safety 🩸 Late cytopenias (>1 yr) ≈ ~13% 🦠 Infections ≈ 40% (COVID, pneumonia) ⸻ ⚠️ Secondary malignancies 📊 ≈ 7.2% ⸻ 🧠 Safety signal ✅ No new long-term safety concerns ⸻ ⚡ Clinical interpretation 🎯 Deep, durable remissions 🧬 Plateau in PFS curve → potential cure fraction ⸻ 🧠 Strategic importance 🚀 CAR-T moves from salvage → potential curative therapy in FL ⸻ ⚖️ Compared to other options 📉 Superior durability vs PI3K inhibitors 📈 Comparable or better vs bispecifics (long-term) ⸻ ⚠️ Limitations 📊 Single-arm study 🧠 Selection bias ⏳ Real-world confirmation ongoing ⸻ 🚀 Future directions 🧬 Earlier-line CAR-T in FL 🔗 Combination with bispecifics 📊 MRD-guided discontinuation ⸻ 📚 Take-home 🧬 Tisa-cel → durable 5-year remissions (~50% PFS) 🔥 Strong efficacy in high-risk FL 🏆 Suggests curative potential in subset ⸻ #Hematology #FollicularLymphoma #CART #CellTherapy #KFSHRC

We recently discussed t(11;14), t(4;14), and t(14;16). Today—let’s simplify what matters most at the bedside: 👉 t(11;14) = “Leaky myeloma” 💧 👉 t(14;16) = “Sticky myeloma” 🧲 Yes… leaky vs sticky. 💧 t(11;14) — LEAKY    •   CD56 negative → no adhesion    •   Cells don’t stay in marrow → spill into blood    •   PB involvement, EMD more common 🧠 Think: No glue → no home → they wander 🎯 Biology: BCL-2 dependent → Target the protein (venetoclax) 🧲 t(14;16) — STICKY    •   MAF → adhesion molecules + IL-6 signaling    •   Early disease: locked in marrow niche    •   Protected, hidden, therapy-resistant 🧠 Think: Glued in place… safe for now 💥 Then evolution happens: → Lose niche dependence → Break out → aggressive EMD 🎯 The big difference:    •   t(11;14) → escapes early    •   t(14;16) → escapes late… and worse ⚡ Clinical translation:    •   Leaky → target the vulnerability (BCL-2)    •   Sticky → disrupt the environment + multi-agent therapy 🧠 If you remember one thing: 💧 If it leaks → shut the valve 🧲 If it sticks → break the niche ✍️ Dr Fun + G #myeloma #hemetwitter

Treatment of Older Adults with Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia karger.com/aha/article/14… #leusm #ALL

Expert Opinion on the Diagnosis and Treatment of Hematologic Malignancies During Pregnancy ascopubs.org/doi/10.1200/JC…

Acute leukemia of ambiguous lineage: the known and the uncertain haematologica.org/article/view/1…

Differentiation syndrome in AML mdpi.com/1422-0067/27/4… #oncology #hematology #AML #medtwitter

Molecular subtypes of DLBCL: are we ready to translate our knowledge into the change of treatment paradigms? ashpublications.org/hematology/art… #lymsm

TP53 in MDS is not binary. It’s a spectrum. And we’re oversimplifying it ! Large SCT dataset confirms: • TP53-mut = adverse • “Biallelic” = worst Important work. But the biology is more nuanced. Monoallelic TP53? Bad. But how bad? We all have long-term SCT survivors → 👉 suggests residual function / heterogeneity True biallelic (multi-hit)? • Functional TP53 loss • Genomic instability • Near chemo-resistant state 👉 Very difficult to rescue, even with SCT But here’s the issue: “Biallelic” often defined as VAF >50% 👉 Useful shortcut 👉 Not biology VAF >50% ≠ biallelic VAF reflects: • Tumor purity • Clonal dominance • Copy number A dominant monoallelic clone can look like “50%” More importantly: 👉 What if TP53 is a 10% subclone? Different biology: • Less genomic dominance • Less clonal fitness 👉 GVL may still control this So TP53-mut disease is not one entity: • Monoallelic dominant • True multi-hit • Small subclonal TP53 ➡️ Different biology ➡️ Different outcomes Retrospective studies like this are critical —but limited by simplified definitions TP53 is a spectrum VAF is not allelic state True biallelic = genomic collapse Subclonal TP53 → may be GVL-sensitive See figure 👇 Dr Fun + G #MDS #AML #Hemetwitter

Current treatment algorithm for DLBCL nature.com/articles/s4140… #oncology #hematology #medtwitter #DLBCL

Myeloma is IRF4–MYC dependent. We talked about steroids. We talked about IMiDs / CELMoDs. Different drugs. Different mechanisms. But look closer… 🧬 Both converge on the same core: The IRF4–MYC transcriptional loop. IRF4 → activates MYC MYC → sustains IRF4 A self-reinforcing program myeloma depends on. Now connect the dots: 💊 Steroids → global transcription ↓ → IRF4 ↓ → MYC ↓ 💊 IMiDs / CELMoDs → IKZF1/3 degradation → IRF4 ↓ → MYC ↓ 👇 Different mechanisms. Same dependence. Dr Fun + G #myeloma #hemetwitter

🔷 Morphological features of acute lymphoblastic leukaemia(ALL) subtypes #LeukaemiaDiagnosisbook

A 2026 update on myelodysplastic neoplasms: current state, challenges and future directions pubmed.ncbi.nlm.nih.gov/41981151/ @Dr_AmerZeidan @NatRevClinOncol #MDSsm @MDSAlliance @ic_MDS @aamdsif @MDS_Hub @MDSFoundation

Acute GVHD is not acute inflammation. It is apoptosis → crypt loss. Case Day 60 post transplant High-volume diarrhea CMV- C diff - ID - 👉 Likely acute GI GVHD → The crypt (stem cell niche) is under attack by activated T cells + cytokines Step 1 — Endoscopy (pattern) • Diffuse vs focal • Ulcer present or not 👉 Diffuse + intact → think GVHD 👉 Focal or ulcer → prove infection (CMV first) Step 2 — Biopsy (mechanism) • Apoptosis → crypt loss → GVHD or MMF • Dense inflammation → infection/colitis • Inclusion (IHC) → CMV 👉 GVHD = epithelial cell death, not inflammation Step 3 — Context • On Cellcept (MMF)? 👉 Can mimic GVHD Bottom line Read the scope Read the crypt Check IHC (CMV) Remember the drug Few cells ≠ low inflammation #GVHD #Hemetwitter

🧬 We used thalidomide for years in myeloma… without knowing why it worked. Not the target. Not the pathway. Just the clinical signal. Now we know—and it’s not chemotherapy. IMiDs are cereblon-directed protein degraders: → Bind CRBN → Degrade IKZF1 (Ikaros) & IKZF3 (Aiolos) From that single mechanism: 🛡️ Immune system ↑ IL-2 ↑ T-cell / NK activation ↓ regulatory T-cell (Treg) function 💥 Tumor cell ↓ IRF4 / MYC → collapse of survival program → cell death 👉 One pathway. Two effects. 👉 Not contradictory—reprogramming biology 🚀 CELMoDs? Same pathway. Stronger signal. → Higher affinity to cereblon → Deeper IKZF1/3 degradation → Activity even after IMiD failure 💡 This is the shift Not: “Does the drug kill the tumor?” But: 👉 “How does it rewire the system?” 👇 Figure: IMiD → immune + tumor effects → CELMoD amplification #myeloma #Hemetwitter

💊✨ Drug Interactions That Decrease High-Dose Methotrexate (HD-MTX) Clearance 👨‍⚕️📚 Credits: Dr. Ahmad Alshamma 🚨 Essential pearls for safe HD-MTX administration in hematology practice: 🔹 💊 Bactrim (Trimethoprim/Sulfamethoxazole) ⚠️ Synergistic antifolate effect & reduced renal elimination ⛔ Avoid within 2 days before and after MTX 🔹 💊 Ciprofloxacin ⚠️ Inhibits renal tubular transport of MTX ⛔ Avoid within 1 day before and after MTX 🔹 💧 Thiazide Diuretics ⚠️ Reduce renal excretion of MTX ⛔ Avoid within 2 days before and after MTX 🔹 🔥 NSAIDs ⚠️ Decrease renal perfusion and MTX clearance ⛔ Avoid if possible; if necessary, hold on MTX day until clearance 🔹 🦠 Penicillins ⚠️ Inhibit renal tubular secretion of MTX ⛔ Avoid if possible; hold on MTX day until clearance 🔹 🌡️ Proton Pump Inhibitors (PPIs) ⚠️ Inhibit renal H⁺/K⁺-ATPase, delaying MTX elimination ⛔ Avoid if possible; hold until MTX clears 🔹 💊 Salicylates (Aspirin, Sulfasalazine, Salsalate) ⚠️ Compete for renal tubular secretion & reduce perfusion ⛔ Avoid within 10 days before and after MTX ✔️ Low-dose ASA (81 mg) may be continued on MTX day if necessary 📊 Clinical Pearls 💧 Ensure aggressive hydration and urine alkalinization 🧪 Monitor MTX levels and renal function closely 🛡️ Administer leucovorin rescue as per protocol ⚠️ Delayed clearance increases risk of nephrotoxicity and myelosuppression #Hematology #Methotrexate #Oncology #PatientSafety #ClinicalPharmacology #HDMTX #MedEd

🔬 Distinction Between Aplastic Anemia and Hypoplastic MDS Credits: Prof. Mahmoud Aljurf, KFSHRC 🩸 Why This Distinction Matters ⚖️ Differentiating Aplastic Anemia (AA) from Hypoplastic Myelodysplastic Syndrome (hMDS) is critical for prognosis, therapeutic decisions, and transplant planning. ⸻ 🧬 Morphological and Clinical Differences 🔹 Dyserythropoiesis 🩸 AA: Sometimes present 🧫 hMDS: Typically present and significant 🔹 Abnormal Neutrophils 🚫 AA: Absent ✅ hMDS: Present (e.g., pseudo–Pelger-Huët anomaly) 🔹 Dysplastic Megakaryocytes 🚫 AA: Absent ✅ hMDS: Characteristic feature 🔹 Bone Marrow Fibrosis 🚫 AA: Absent ⚠️ hMDS: Occasionally present 🔹 Increased Blasts 🚫 AA: Absent ⚠️ hMDS: Sometimes increased; may show ALIPs (Abnormal Localization of Immature Precursors) 🔹 CD34⁺ Cells in Bone Marrow 📉 AA: Typically <1% 📈 hMDS: Often increased 🔹 Clonality 🧬 AA: Possible (e.g., PNH clones) 🧬 hMDS: Clonal hematopoietic disorder 🔹 Splenomegaly 🚫 AA: Typically absent ⚠️ hMDS: Occasionally present ⸻ 🧪 Cytogenetic and Molecular Features 🔬 Aplastic Anemia •Usually normal cytogenetics •May harbor PNH clones •Somatic mutations: PIGA, BCOR, BCORL1, DNMT3A, ASXL1 🔬 Hypoplastic MDS •Abnormal cytogenetics are common •Typical abnormalities include del(5q), monosomy 7, trisomy 8 •Mutations: SF3B1, SRSF2, TET2, RUNX1, TP53, ASXL1 ⸻ 🧠 Diagnostic Pearls 🎯 Marked dysplasia favors hypoplastic MDS. 🎯 Increased blasts and ALIPs suggest MDS. 🎯 Profound hypocellularity without dysplasia supports aplastic anemia. 🎯 Increased CD34⁺ cells indicate clonal hematopoiesis. 🎯 Presence of PNH clones supports AA. 🎯 Splenomegaly is uncommon in AA. 🎯 Cytogenetic abnormalities strongly favor MDS. ⸻ 💊 Therapeutic Implications 🩺 Aplastic Anemia •First-line: ATG + Cyclosporine ± Eltrombopag •Curative option: Allogeneic HSCT 🧬 Hypoplastic MDS •Risk-adapted therapy based on IPSS-R/IPSS-M •Options include hypomethylating agents, immunosuppressive therapy in select cases, and HSCT ⸻ 📚 Key References 🔗 Bennett JM et al. Seminars in Hematology. 2000;37:15–29. 🔗 Bennett JM, Orazi A. Haematologica. 2009;94(2):264–270. 🔗 Hama A et al. Rinsho Ketsueki. 2011;52(8):653–658. 🔗 Young NS. Aplastic Anemia. Blood. 2018. ashpublications.org/blood/article/… 🔗 NCCN Guidelines for Myelodysplastic Syndromes. nccn.org ⸻ #Hematology #AplasticAnemia #MDS #BoneMarrowFailure #HypoplasticMDS #HSCT #KFSHRC