Summary of cytoplasm/nucleus changes in leukocytes:
1️⃣ Hyposegmentation of neutrophils(peanut shaped, bilobed,or non-segmented nucleus with coarse chromatin)
🔬associations: Pelger–Huët anomaly(inherited) or pseudo-Pelger–Huët anomaly(acquired)
➡️Pelger–Huët anomaly(inherited):affect majority of granulocytes: autosomal dominant- mutations in the lamin B receptor gene
➡️Pseudo-Pelger–Huët anomaly(acquired): <50% of granulocytes: usually occurs with other morphological changes of malignancy: can see in MPNs or MDS #Heme
2️⃣Hypersegmentation of neutrophils
➡️≥ 6 lobes in granulocyte nucleus
🔬associations: megaloblastic anemia, chronic infections, MDS, familial(rare) #Heme
3️⃣ Vacuolation in neutrophils
➡️Unstained circular area within the cytoplasm
🔬associations: bacterial/fungal infections, burns, poisoning chemotherapy use, artifact
(monocytes can have vacuoles=Normal) #Heme
4️⃣ Döhle body
➡️grey/blue inclusion in the cytoplasm of neutrophil
🔬associations: bacterial infection, sepsis, pregnancy, May–Hegglin anomaly #Heme
5️⃣ Toxic granulation
➡️dark purple-black granules in the cytoplasm of neutrophil
🔬associations: bacterial infections, sepsis, after G-CSF
(Note: can occur with Döhle body in the same neutrophil) #Heme
6️⃣ hypogranulation/agranulation of neutrophils
➡️ low or absence granules in the cytoplasm
🔬associations: MDS,MPN, infections
7️⃣ Reactive lymphocytes
➡️ usually indented cytoplasm by adjacent cells
🔬associations: viral infections including infectious mononucleosis, after organ transplantation
(can also have radial basophilia,vacuolated cytoplasm)
#mmsm
How to counsel patients about Cilta Cel using the data from
CARTITUDE-4 and FDA ODAC meeting for earlier use
With data of Cilta cel and Ide cel, assuming having access to both for a given patient, I will personally chose Cilta cel (I explained this before)
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In the first ~6 months after we plan to give you Cilta-cel, you have one out of 12 (8%) chances of dying either of progressive disease or adverse event to Cilta cel, this will depend on the bridging therapy we will use and your response to it (planning is important to ⬇️risk)
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If you are able to get your Cilta cel, the risk of death in the first 3 months is 5% , most of those deaths (4%) were related to adverse events. Given the study was done in COVID era, some of the deaths were related to that infection so the risk maybe lower nowadays-esp USA
✅Phase II trial of Dara-RVd vs. RVd
✅Final analysis after all pts had completed at least 1 year of follow-up after end of study ttt, had died, or withdrew from study participation.
➡️stringent complete response rate by end of post-HSCT consolidation
➡️Very important portion of the study 👇
➡️Assumption is 15% difference between Dara-RVd vs. RVd.
Note that statistical significance can be ascertained for 1ry endpoint
Did the study meet the 1ry endpoint?
sCR post transplant
Dara-RVd: 42%
RVd: 32%
Difference of 10% only
This means study didn't meet 1ry endpoint
Now the assumption for power calculation was 35% sCR in RVd group which was actually less in the study so this is not the reason.
✅ modulator of E3 ubiquitin ligase complex containing cereblon
✅ binds to cereblon and subsequently induces proteasome-mediated degradation of certain transcription factors➡️ activation of T-cells
✅Pts on expansion cohort were triple class refractory👇
🛑Plasmacytoma was 40% (extramedullary soft-tissue only and bone-based plasmacytomas with a measurable soft-tissue component)
✅weekly Dex 40 mg (for pts >=75 yrs 20 mg)
✅phase II dose is 1 mg daily for D1-21/28 days
🛑17 of 196 (~9%) of patients who did not proceed to CAR T-cell infusion because of either disease progression/death (n = 12) or manufacturing failure (n = 5) were excluded from the final efficacy analysis👇
➡️ It is important to note that excluding pts who progress while waiting for CAR-T will not reflect the actual real world efficacy of CAR-T therapy
🛑We are adding layers of selection bias:
✅intent to manufacture
✅intent to treat
Notice the PFS/OS curves👇