MDS Flashcards
Common NGS defects in MDS-MLD (multi-lineage dysplasia)
TET2, SF3B1, ASXL1, SRSF2, DNMT3A (also TP53 and ETV)
Issues in the stomach, duodenum, TI and post absorption that may lead to Vitamin B12 deficiency.
a. Stomach: Achlorhydria, gastrectomy/bariatric surgery, H. pylori, PPI, H2 blockers
b. Proximal duodenum: Lymphoma, IBD, pancreatic insufficiency, metformin, celiac, tape worm
c. Terminal ileum: IBD, resection, Imerslund-Gräsbeck
d. Post absorption: Transcobaalamin II deficiency
Others: vegan, pernicious anemia, congenital IF def
Name 4 (adverse) effects of lenalidomide treatment in MDS.
*used in transfusion dependent 5q and some response (~25%) in those with non-5q del,low risk MDS.
Neutropenia ** Anemia Thrombocytopenia ** VTE Infection Diarrhea Rash Fatigue
What are the two cytogenetic abnormalities associated with very good risk MDS?
del Y, del 11q
What are the two cytogenetic abnormalities associated with good risk MDS?
Normal, del 5q, del 12p, del 20q,
What are the two cytogenetic abnormalities associated with intermediate risk MDS?
del7q, +8, i17q, +19
2 or more ind clones
What are the two cytogenetic abnormalities associated with poor risk MDS?
Abnormal 3q, del 7, double -7/del7q, complex up to 3 abnormalities
What is one cytogenetic abnormality associated with very poor risk MDS?
Complex karyotype with >3 or more abnormalities
MOA of Luspatercept
Erythroid maturation (not production) agent.
- Neutralizes select TGF-B- superfamily ligands to intercept/inhibit SMAD 2/3 signalling
- The reduction in SMAD signaling leads to enhanced erythroid maturation.
BELIEVE trial in Beta- thal, MEDALIST in MDS
Poor prognosis point mutations in MDS?
Poor prognosis: READ T
RUNX1 EZH2 ASXL1 DNMT3A TP53
SF3B1-good outcome
Others: TET2 (better response to AZA), IDH1, IDH2
Which pts are more likely to respond to ESAs in MDS?
- low transfusion requirement (< 2 units/month)
- low endogenous pretreatment plasma EPO level (< 500 U/L)
- < 10% bone marrow blasts
- low/intermediate-1 (int-1) risk International Prognostic Scoring System (IPSS).
*not FDA approved
Why is Romiplostim not recommended for use in MDS ?
- Increased blast percentage (reversible with holding or stopping)
- Increased progression to leukemia
Explain the process by which ferric iron, bound to transferrin enter the apical membrane of enterocytes.
Fe3+ (ferric) bound to transferrin—> bind to transferrin receptor (TFR1)—> to be stored/transported, it must be reduced to Fe2+ form by Duodenal cytochrome b (Dcytb)–>endocytosis by DMT1 which releases Fe2+ from the Tf-TFR1 complex and escorts to cytoplasm—> Then must be re-converted to Fe3+ before exciting the basolateral membrane into portal circulation via ferroportin.
Causes of isolated elevated homocysteine level
- Folate def
- Hypothyroidism
- Vitamin B6 def (pyridoxine)
4 medications which cause macrocytic anemia?
- MTX
- HU
- 5-FU
- Aziothioprine