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
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
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
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
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
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
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
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
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
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
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
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…
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.
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
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
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
There are currently 4 JAK inhibitors for MF:
ruxolitinib
fedratinib
pacritinib
momelotinib
Let's quickly present them, followed up by #ASH22 abstracts. 3/17
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.
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
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.
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. "
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_ASCOascopubs.org/doi/full/10.12…
Congrats to all !
It's a tricky one. A🧵#leusm#bmtsm#mdssm
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.