Queuing up Dr. Kwiatkowski's of @CHOP_Research giving updated results of the #HGB-206 lentiglobin gene therapy for #sicklecelldisease in today's plenary session at #ASPHO2021. Follow this thread for more 1/n Image
Why are we talking about gene therapy for #sicklecell. It's estimated <15% of patients have a sibling matched stem cell transplant donor! 2/n
Today's talk is going over group C - eligibility included here. Enrollment has been completed. This is for SS and S beta0 and S beta+ genotypes. 3/n Image
Lentiglobin modified stem cells are infused after busulfan myeloblative conditioning. There will be 13 years of long term follow-up - 32 have completed infusion thus far with 13 month follow-up. Image
Complete resolution of the VOE's 6 months after post-lentiglobin treatment in these patients. Of note, you can follow HbA^T87Q is the transduced product - its's in Red here. Median hgb ~11 at 6 months 5/n ImageImage
Markers of hemolysis significantly improved (to near-normal) - retic, LDH, and total bilirubin. 6/n
Safety data is important for our patients - see this slide for more. No insertional mutagenesis. Many adverse events related to treatment with conditioning regimen. 7/n Image
There is a CLINICAL HOLD on bluebird bio studies with bb1111 (this lentiglobin therapy). See details of this below -- transfusion dependent anemia is the revised diagnosis for the prior reported MDS case possibly related to the lentiglobin therapy. More information is needed! 8/n Image
And the conclusions -- Thank you Dr. Kwiatkowski for your summary of this result. Stay tuned for Q&A. 9/n Image
Q&A thoughts: a) Adol had higher Hgb levels (~13) - still need more numbers to figure out why. b) Busulfan is myeloablative so they anticipated it can/will impact fertility and fert. preservation was offered/taken up by all patients. 10/n
c) Allowed stroke pts initially but subsequently did not allow -- but as of now, no cases of stroke. d) Asking whether the two cases that led to the hold was above busulfan-related known rates. Says it's unclear at this point - concerning that we've seen a couple events. 11/n
e) The patient with AML has checked where integration occurred - in the AML blasts there was insertion in VAMP4 gene (but no known association in this gene with cancer per their review) but this doesn't mean that the gene therapy wasn't the problem - must research more. 12/n
Of note, they are checking every 6 months for insertional data collection and monitoring closely.
Okay, that's it folks! Stay tuned and follow me for more from #ASPHO2021. 13/13 (end!)

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More from @DrTiffanyL

22 Apr
Dr. Sidonio reviewing treatment decisions re: inhibitor patients in the #emicizumab era at #ASPHO2021 - starting with a reminder about bypassing agents and their unique dosing 1/n Image
ITI (high dose factor exposure) is the standard for getting rid of inhibitors -- worse success if historical high peak titre, time since dx of inhibitor, etc. 2/n
But despite that it's expensive, burdensome... all the major organizations nationally and internationally say you should attempt it! 3/n Image
Read 5 tweets
22 Apr
Now for an update on #TTP -- always a disease I enjoy teaching about -- the pathophysiology combines so much #heme goodness. Also, I always enjoy the summary slide up front from Dr. George. #ASPHO2021 1/n Image
For those studying for boards in the future... this is the classic TTP blood smear! #mededpearls #TTP #ADAMTS13 #ASPHO2021 2/n Image
Hereditary TTP management summarized here -- nice to have it on one slide! 3/n Image
Read 5 tweets
22 Apr
Up next - Update on TMA! (thrombotic microangiopathy) at #ASPHO2021 Thread here 1/n
Transplant associated-TMA (TA-TMA) defined here. Look at the labs that you should use to help guide this diagnosis. High risk criteria of TA-TMA on second slide. 2/n ImageImage
TA-TMA have a really high morbidity with a lot of multiorgan injury (intestinal, pulmonary, CNS)... scary -- I don't see this often (since I am no longer working in transplant patients) but the information can be translatable to other TMA type processes. 3/n Image
Read 6 tweets
22 Apr
35% of children in the US qualify for coverage with Medicaid/CHIP
70% of #sicklecell patients have Medicaid/CHIP (!!!!!)

We think that brings equality because Medicaid/CHIP brings access to care (but not all physicians accept patients with Medicaid/CHIP).

#ASPHO2021 1/n
Why is this important? Because patients with sickle cell disease have a decrease life expectancy! (by 30 years!) Not only that -- Dr. Allison King found that patients with #sicklecell saw that those on Medicaid clearly repeated grade levels. #ASPHO2021 2/n
From the SIT trial - silent cerebral infarcts wasn’t the risk factor.. per capita income was! Look at the OR of 6.4 for those in the lowest quartile. The most at risk are our older males. #ASPHO2021 3/n Image
Read 6 tweets
21 Apr
Management of iron overload for #phodocs to pay attention to. Talk by Dr. Lalefar from @UCSFBenioffOAK. Follow this thread 1/n Image
Who should be monitored for iron overload? Those that have a transfused volume >100 ml/kg (~10 transfusions) #ASPHO2021 2/n
Dr. Lalefar suggests checking ferritin, but remember to check with other iron studies. She says a serum ferritin >1000 ug/L is the common threshold used. (But this was based on correlation studies with liver iron from mostly Caucasian hemochromatosis patients) 3/n
Read 11 tweets
21 Apr
Peak risk of catheter associated DVT at 4 days after catheter insertion. The CRETE trial used ppx enoxaparin on day one (target 0.2-0.5 anti-Xa level) and showed may be able to prevent DVT. 1/n Image
But amongst infants (child <1 year) no real change in risk - but older children have risk reduction from Dr. Faustino's CRETE trial. He suggests due to differences in size of line versus vein size (infants have less delta) 2/n Image
Infants have lower thrombin generation which may be why ppx enoxaparin may not help them as much -- they then thought about trying therapeutic enoxaparin in infants to prevent CA-DVT. 3/n
Read 6 tweets

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