Two oral abstracts on the #STELLAR study (Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry) presented by Dr. Sobenna George (hi!) and Dr. Lillian Meacham #ASH22 1/n What's the problem? You can get DOR = diminished ovarian reserve or POI = primary ovarian insufficiency (early menopause). This is SUCH a good explanation!! #ASH22 2/n

How many patients are on disease modifying treatments for #SCD - data from 2014-2021 presented by Dr. Terri Newman. @ash22 1/n We're talking about #Hydroxyurea and in 2017, expanded use of #HU as well as L-glutamine and then in 2019 #voxelotor and #crizanlizumab. #ASH22 2/n

Management of pregnant women with #SCD in high income countries with Dr. Eugene Oteng-Ntim (with the cutest intro from Dr. Eugenia Asare). Writing down the #pearls here so I can share with my patients for their future and so I can advocate for them. #ASH22 1/n As we know, more low/not detectable AMH levels in women with #SCD. Know that preimplantation diagnosis and successful transfer is possible with data to support that. And many want #NIPT secondary to fear of amnio or CVS, which can be done. (w/ @Nonacus) #ASH22 2/n

Dr. Mark Fleming talking about pathology vs molecular testing in MDS. He first reminds us the difference of childhood MDS from adult MDS -- and these WHO guidelines, childhood MDS is only classified into these two subtypes. #ASH22 1/n The issue is that the "dysplasia" definition has been defined by the cytogenetic abnormalities and genotypes of adult MDS so the criteria for blast %age, extent of dysplasia -- but does this apply?? #ASH22 2/n

#ASH22 Bone marrow failure syndromes: diagnostic principles in 2022. Starting with Sara Lewis, a genetic counselor in hematology. Follow this tweet for more. 1/n Sara reminds us that she feels patients think more about their family history as they see her draw the pedigree. Time for me to start doing this! #phodocs #ASH22 #pearl 2/n

@bhwords Dr. Beverley Hunt presenting on #COVID19 and #thrombosis. She wants to chronologically review the battles we have fought! #ASH22 1/n @bhwords This story (clinical presentation) -- a reminder of the patients from the front lines in the beginning and what some docs went through! #COVID19 #ASH22 2/n

@MiddeldorpS starting with a big thank you :) Great job starting off with these #ASH22 difficulties. 1/n @MiddeldorpS #ALIFE2 study of low molecular weight heparin vs standard pregnancy care RCT for recurrent miscarriage (2+) and inherited thrombophilia - 41 centers in 5 countries! #ASH22 2/n

@redcell_doc talking about #SCT and #VTE in a #23andme cohort! Check it out here. #ASH22 1/n @redcell_doc Sickle cell DISEASE has a unique reason for thromboembolism -- PE predominance - in situ or embolism from legs? Unclear still. But we know #SCT patients have higher D-dimer levels so maybe there's a hint for more in trait patients. #ASH22 2/n

Now back to learn about sickle cell trait #SCT from Faeben Wossenseged, BS. Their participants were mostly female. Retinopathy and hematuria seen in their results! 1/n Amazing database available and they found 2.45% sickle cell trait carriers - reminds them we need to figure out how to do better #SCT carrier screening and know better how to counsel about this entity. #ASH22 2/2

@SharonSavageMD presenting on #DyskeratosisCongenita #DC update. Starting a pt presentation with a de novo TINF2 variant. #ASH22 1/n @SharonSavageMD She mentions her GI bleeding (as well as other findings) -- something I have seen in #DC. What we know - females do better than male (due to X-linked disease) #ASH22 2/n

#Voxelotor #SCD real world outcomes Q&A -- Q: what about concurrent HU vs not? A: we have thatdata, will get to it! 1/n Q: what about stroke? A: it's mostly in pediatrics, and dataset is limited so REALLY important, but not from this data just yet. Here are his conclusions. 2/n

Dr. Carlo Dufour for the latest and modern management of #FanconiAnemia. #ASH22 1/n When to think about Fanconi anemia? Remember that genetic testing may be difficult to interpret and can be inconclusive - so correlation with clinical/functional studies is required. #ASH22 2/n

Will be jumping around this afternoon -- but starting off with "Hormonal Contraceptive Use and Association with Thromboembolism in Women with Sickle Cell Disease" with Dr. Natasha Bala. I feel like this is gonna be a good one! Tune in below. #ASH22 1/n Combined OCPs is a category 2 -- meaning the benefit outweighs the risks. Their hypothesis was that risk of thrombosis was higher with combined OCPs versus progesterone only. #ASH22 2/n

Moving over to the ASH #ChoosingWisely campaign because this title definitely caught my attention (reducing unnecessary premeds for parenteral iron therapy)! #ASH22 @ASH_hematology props for making this a session. 1/n @ASH_hematology Introducing Dr. Carol Mathew @CarolMathewMD from University of Florida. Some background, they have an infusion center with 47 chairs (on the onc floor - haha) with 3000+ iron infusions. #ASH22 2/n

@AkshaySharmaMD now up! Check out his QR code his slides below. Thanks for sharing. Will try to do a quick summary in this thread 1/n #ASH22 @AkshaySharmaMD This product has guideRNA for cas9 cutting at these two sites -- indels at the HGB1 +/- HGB2. Found 80-85% indel deletion in preclinical validations. Eligibility for the study here. #ASH22 2/n

Dr. Alan Anderson here to present #crizanluzumab (which is approved for age >16 to prevent VOE) and its effect on #priapism. Long prescreening to capture these occ events. Needed 4 in prescreening 14 weeks. 1/n #ASH22 24 patients met the eligibility criteria. Received 5 mg/kg and then q4 weeks and checked outcome at week 26 and treated for 52 weeks. Also reported #PRO. #ASH22 2/n

Another FVIII variant to tune into Dr. Denise Sabatino from CHOP because we are all looking to do the following in 2nd gen AAV gene therapy. Follow this thread to learn more (read my prior one on #FVIII-QQ from yesterday also) #ASH22 1/n Canine FVIII has increased expression due to a variant of the furin and a3 cleavage site which they put into this product (using AAV8 vector). (known as delta3-SP/BDD) #ASH22 2/n

@CroteauMD up next on multiyear follow-up on SPK-8011 - an AAV vector factor 8 product. Note that the doses have been much lower than other doses investigated. Must know this as you compare these gene therapies in #hemophiliaA #ASH22 1/n @CroteauMD Tiny font but she is pointing out the stable lines for the activity over the years (5 years of data) -- but also to my eye the variability based on same vector doses depending on the patient. #ASH22 2/n

Telomere length elongation ex-vivo in a patient with #dyskeratosiscongenita? #DC Presentation by Dr. Kasiana Myers #ASH22 1/n Utilizing ZSCAN4 - a protein that enhances genome stability and regulates telomere elongation in EXG-001 -- a non-integrating temperature-sensitive non-transmissible Sendai virus vector. #ASH22 @KMyersBMT 2/n

Dr. Anna Sternberg from CHOP presenting on a study on "Factor VIII-QQ" = FVIII variant resistant to activated protein C (APC) cleavage w/ normal specific activity & 4-5x improved hemostatic function in recombinant protein experiments (Wilhelm et al. Blood 2021). #ASH22 1/n With same dose of AAV-hFVIII wild type vs AAV-hFVIII-QQ you get improved hemostatic effect and 5-6x plasma FVIII activities. Why? see next on this thread. #ASH22 2/n

And then he took from chapter 1 and applied it to chapter 2 - found that he could assess for mixed chimerism using restriction length polymorphism. And then.. time to find a job! And he wanted to bring it in to the clinic, so... #ASH22 6/n Always love showing photos of the researchers earlier in their careers! So then he was able to establish a mouse a model of graft rejection. And tried in vivo cytokine injection to increase graft - tried lots of them, some toxic, some didn't work. 7/n #ASH22