MDS Flashcards
Meaning of Auer rods
MDS excess blasts
common RBC morphology on blood smear
Ovalomacrocytosis
also: Basophilic stippling Howell-Jolly bodies Megaloblastoid nucleated RBC Elliptocytes teardrop cells Atomatocytes Acanthocytes
Cytogenetic abnormailties-unbalanced
Loss of chromosome 7 or del(7q) del(5q) or t(5q) Isochromosome 17q or t(17p) Loss of chromosome 13 or del(13q) del(11q) del(12p) or t(12p) del(9q) idic(X)(q13)
BM myeloid morphology
relative maturation arrest
abnormal localization of immature precursors (ALIP)- immature cells cntered centrally and not peripherally
BM erytroid morphology
ineffective erythropoiesis
large RBC
nuclear multilobation and budding
cytoplasm- vacuolization, PAS positive granules, ring sideroblasts
BM megakaryocyte morphology
usually normal
Large, small (“dwarf”/micromegakaryocyte), multiple dispersed nuclei ( “pawn ball megakaryocytes”), hypogranular
BM fibrosis
up to 50%
usually mild-moderate
Cytogentic abnormaility- balanced
t(11;16)(q23.3;p13.3) t(3;21)(q26.2;q22.1) t(1;3)(p36.3;q21.2) t(2;11)(p21;q23.3) inv(3)(q21q26.2) or t(3;3)(q21.2;q26.2) t(6;9)(p23;q34.1)
cytogenetic abnormailtes diagonstic of AML
t(8;21)(q22;q22); RUNX1-RUNX1T1 (previously AML1-ETO)
inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
t(15;17)(q22;q21.1); PML-RARA
WHO Classification criteria
MDS with single lineage displasia
MDS with multi-lineage displasia
MDS with ring sidroblasts (>15%)
MDS with isolated del(5q)
MDS with excess blasts 1 (BM 5-9%, PB 2-4%)
MDS with excess blasts 2 (BM 10-19%, PB 5-19% or Auer rod)
MDS uncalssifiable
SF3B1
Associated with ring sidroblasts
favorable prognosis
DD of ring sidroblasts
Alcohol Benzene Lead Isoniazid Copper deficiency Congenital
MDS with del(5q)
Macrocytic anemia w/wo trombocytosis
Usually no neutropenia
Pretty benign
DD of MDS
Deficiency of vitamin B12, folate, or copper
Zinc, lead or arsenic poisoning
HIV
VEXAS
IPSS-R
Cytogenetics Blasts HB ANC PLT
Molecular prognostic associations
Adverse – ASXL1, SRSF2, DNMT3A, RUNX1, U2AF1, TP53, EZH2, STAG2, CBL, NRAS, BCOR
Favorable – SF3B1
Neutral or uncertain – TET2, ZRSR2, IDH1, IDH2
Clinical prognostic factors
age
Performance status
number and severity of cytopenia
Timing of IPSS-R assessment
At diagnosis
Outcomes by risk
Very low risk (≤1.5 points) – 8.8 year OS; >14.5 years to 25 percent AML Low risk (>1.5 to 3 points) – 5.3 year OS; >10.8 years to 25 percent AML Intermediate risk (>3 to 4.5 points) – 3.0 year OS; 3.2 years to 25 percent AML High risk (>4.5 to 6 points) – 1.6 year OS; 1.4 years to 25 percent AML Very high risk (>6 points) – 0.8 year OS; 0.7 year to 25 percent AML
Lower-intensity therapies
EPO, TPO Luspatercept, Hypomethylating agents IDH inhibitors Immunosuppressive therapy lenalidomide
Lower-intensity therapies
EPO, TPO
Lusbatercept
Hypomethylating agents
IDH inhh
Treatment of low risk
Asymptomatic- supportive care
Symptomatic- lower-intensity therapies
Treatment of high risk
Medically fit- allogenic-HSCT
Unfit, not frail- lower-intensity therapies
frail- supportive care
Anemia treatment in low risk
if EPO < 500 - ESA
if EPO> 500 - HMA
Thrombocytopenia Tx in low risk
TPO-RA
unless excess blasts
Tx of MDS-RS
Luspatercept
Tx of del(5q)
Lenalidomide
Luspatercept mechanism
Inhibition of TGF-β
Features associated with immunosuppressive therapy responsiveness
Age <60 years ≤5 percent blasts Hypocellular bone marrow PNH-positive clones, STAT3-mutant T cell clones
Immune suppressive therapy
ATG + cyclosporine
Luspatercept indication
MDS-RS
IDH inhibitors
Ivosidenib
Enasidenib
Tx og high risk
Allo- HSCT Induction chemo (3+7) w/wo allo HSCT low intensity therapies
