Nico Gagelmann Profile picture
Nov 10 16 tweets 11 min read
A phrase many of us have used:
"Allogeneic BMT is the only curative treatment for various diseases but associated with morbidity/mortality."

Evidence & local practice are often heterogeneous. Can this year's @ASH_hematology meeting guide us?

🧵with #ASH22 abstracts

#MedTwitter Image
Mini intro to BMT:
-replaces damaged blood or bone marrow cells with healthy ones from donor
-source: peripheral blood or marrow (usually hip)
-matched related, matched unrelated (MUD), mismatched related, mismatched unrelated donors

In that spirit: go register & save lives!
/1 Image
Let's categorize the #ASH22 thread chronologically along the path to and from allogeneic BMT:
-to transplant or not to transplant?
-donors
-conditioning
-graft-versus-host disease (GVHD)
-follow-up
Focus on adults, not a pediatrician. Respect to all in #Pediatrics btw!
/2 Image
To BMT or to not BMT? part 1 #ASH22
-plenary
-chemo (high-dose cytarabine and mitoxantrone) before BMT with no survival advantage
-watchful waiting followed by sequential conditioning and BMT with comparable survival
-start donor search at diagnosis! ash.confex.com/ash/2022/webpr…
/3 Image
To BMT or to not BMT? part 2 #ASH22
-randomized trial, n=245
-BMT is superior to non-BMT consolidation treatment for leukemia-free survival in elderly acute myeloid leukemia patients in first complete remission, 5year follow-up ash.confex.com/ash/2022/webpr…
/4 Image
Which donors? #ASH22
-study from @CIBMTR
-significant relapse reduction with younger MUD versus older matched sibling donor
-higher treatment-related mortality with younger MUDs has decreased in recent years ash.confex.com/ash/2022/webpr…
/5 Image
Which conditioning? #ASH22
-novel regimen with fludarabine, cyclophosphamide, rituximab in severe aplastic anemia
-0% non-relapse mortality and 100% disease-free survival with low GVHD rates at 1-year post-transplant ash.confex.com/ash/2022/webpr…
/6 Image
Which GVHD prophylaxis? part 1 #ASH22
-@CIBMTR
-no significant difference in late graft failure rates when utilizing a haploidentical versus MUD with postBMT cyclophosphamide in patients undergoing reduced intensity BMT for AML, ALL or MDS ash.confex.com/ash/2022/webpr…
/7 Image
Which GVHD prophylaxis? part 2 #ASH22
-@TheEBMT study
-methotrexate + calcineurin inhibitor prophylaxis was associated with favorable early survival and treatment-related mortality in patients with chronic myeloid malignancies or secondary AML ash.confex.com/ash/2022/webpr…
/8
Which GVHD prophylaxis? part 3 #ASH22
-using abatacept compared with ATG or postBMT cyclophosphamide appears to improve survival
-compelling results but validation and longer follow-up needed ash.confex.com/ash/2022/webpr…
/9 Image
How to treat GVHD? #ASH22
-ruxolitinb (5 mg/day) + methylprednisolone (1 mg/kg) as effective first-line therapy
-high overall response rate
ash.confex.com/ash/2022/webpr…
/10 Image
Maintenance after BMT? #ASH22
-pilot study of enasidenib maintenance therapy resulted in promisinge survival outcomes in AML patients carrying IDH2 mutations
-however, treatment delay and dose reductions were common
ash.confex.com/ash/2022/webpr…
/11 Image
How to care after? #ASH22
-compared to usual care, shared care with local providers led to improved quality of life
-results a no-brainer but possibly for US system quite relevant
->in care, we need to take into account different healthcare systems! ash.confex.com/ash/2022/webpr…
/12 Image
High-risk & long-term outcome? #ASH22
-BMT is associated with improved long-term outcomes in patients with TP53 AML
-significantly better among patients who were in complete remission at day 100 post BMT or had cGVHD
-should be offered to eligible patients ash.confex.com/ash/2022/webpr… Image
In conclusion, timing of BMT is everything and disease control the most important factor for success. We have new options for GVHD, time for large comparative trials to finally standardize our BMT community. Still, let's not forget the different healthcare realities we live in.

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More from @NicoGagelmann

Nov 9
CAR T-cells have huge potential for multiple #myeloma.

It's an individualized treatment, complex process, associated with high costs->risk for huge inequality worldwide.

Lets advocate for hope & improvement, together.

🧵on what's new with #ASH22 abstracts

#MedTwitter #mmsm
Mini background of CAR:
-designer proteins that redirect T cells towards a defined surface antigen on tumor cells
-construct contains four essential components
--extracellular antigen recognition
--hinge, spacer
--transmembrane domain
--intracellular signaling domains
Let's categorize the overview of #ASH22 abstracts to structure &sharpen our minds:
C-clinical results in relapsed/refractory #myeloma
E-earlier lines of treatment
R-refined design
A-adverse effects after CART infusion
D-disparities

Shout out to Alzheimer's community! /1
Read 18 tweets
Nov 8
The wonderful thing about @ASH_hematology Annual Meetings is the fruitful mix of clinic and basic research presentations.

Let's finish off our myelofibrosis coverage about new insights into biology and potential therapeutic targets.

🧵with #ASH22 abstracts

#MedTwitter #mpnsm
Short background:
-driver mutations JAK2, CALR or MPL in 90%
-in concert with epigenetics (eg ASXL1, DNMT3A, SRSF2...)
-aberrant megakaryocytes as quintessence->reduced GATA1 protein expression and plethora of pro-inflammatory cytokines & extra-cellular matrix components 1/15
Now let's go to #ASH22 abstracts covering the following entities of myelofibrosis biology:
D - driver mutations
O - other mutations
C - cell interaction
I - inflammation

For @starwars fans👇2/15
Read 17 tweets
Nov 6
You read a lot about "novel" drugs in myelofibrosis.

But you need to know how to walk before you fly.

JAK inhibitors were the first to revolutionize myelofibrosis treatment.

Let's recap what they are & what we still dont know.

🧵with #ASH22 abstracts

#MedTwitter #mpnsm Image
Janus kinase:
-intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway
-name taken from the 2-faced Roman god of beginnings, endings and duality, because JAKs possess near-identical phosphate-transferring domains 2/17 Image
There are currently 4 JAK inhibitors for MF:
ruxolitinib
fedratinib
pacritinib
momelotinib

Let's quickly present them, followed up by #ASH22 abstracts. 3/17 Image
Read 18 tweets
Nov 4
Let's talk about bone marrow fibrosis in myelofibrosis.

When we hear fibrosis, we think lung (IPF) or liver (cirrhosis), devastating conditions.
The beauty about marrow fibrosis: it's reversible with allogeneic BMT.

Let's start🧵with new #ASH22 abstracts

#mpnsm #MedTwitter /19
Bone marrow fibrosis (BMF) is characterized by the increased deposition of reticulin fibers and in some cases collagen fibers. Scoring of BMF is primarily dependent on manual grading by the hematopathologist based on the density and type of fibrosis. 1/19
Besides myelofibrosis, there are several hematologic and non-hematologic disorders that are associated with increased BMF that differ in composition (either reticulin-only or reticulin plus collagen). 2/19
Read 22 tweets
Oct 4
Dear #MedTwitter, finally got an interview with the amazing @Sthanu5. He was not comfortable doing an audio or video, which I respect. Therefore, here is a written conversation with him.

"@Sthanu5 in 10 boluses"
1. What is your background? Where did you train?
"I am a first-generation doctor with no medical background. Did my under-graduation in Tirunelveli medical college and PG in Institute of child health in Chennai, Tamilnadu."
2. Where are you currently located?
"Doing my pediatric practice here in Tuticorin in south Tamilnadu, India. Running a hospital with fairly tight schedule. "
Read 12 tweets
Jul 12
Long awaited study (at least for me) on maintenance after hematopoietic cell transplant (BMT) for patients with TP53 acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS) @JCO_ASCO ascopubs.org/doi/full/10.12…
Congrats to all !
It's a tricky one. A🧵#leusm #bmtsm #mdssm
Prologue: TP53 mutation is present in ~15-20% and is associated with a poor prognosis in AML and MDS, even in patients who undergo BMT. acsjournals.onlinelibrary.wiley.com/doi/10.1002/cn… Image
Eprenetapopt is a prodrug, small-molecule p53 reactivator, converted into an active moiety, 2-methylene quinuclidine-3-one, stabilizing p53 and targets cellular redox balance to increase oxidative stress & induce cell death.
Read 14 tweets

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