Back to the basics
Define MDS?
MDS is a Clinical and Morphologic Diagnosis.
• At least one cytopenia: • Hb <13/<12g/dl (m/f) • Platelets <140x109/l • WBC <1.8x109/l
• Dysplasia >10% in at least one lineage
• ↑ Blasts; ↑ Ringed sideroblasts
• MDS-defining karyotype or SF3B1 or biallelic TP53
Gemtuzumab Ozogamicin MOA? Toxicities?
CD33 monoclonal Ab [CD33 is present on >90% of AML blasts]
Tox--hepatotoxicity & VOD
Which MDS patients don't require any treatment?
Patients with good features and good cytogenetics.
Good Features--Hb >10, Platelets >100, ANC>0.8, Blasts <2%
Good cytogenetics-- del(5q), del(11q) del(12p) del(20q)
Low IPSS/R/M score
What do you give if the patient with MDS has anemia and serum EPO levels of > 500
Luspatercept--It is a fusion protein that promotes Late-Stage Erythropoiesis to Alleviate Anemia.
Given if
- MDS has anemia and serum EPO levels of > 500
- MDS-RS
True/False
SF3B1 Mutations in MDS is associated with good prognosis.
True!
SF3B1 Mutations are associated with an indolent course and a more favorable outcome in MDS.
Mutation found in 20% of MDS cases and this gene involved in RNA splicing machinery.
Which patients with AML needs LP?
WBC>=30 K
Monocytic leukemia
FLT3 mutation
MDS with Isolated del(5q) responds to which medication?
Adverse effects of that medication?
Lenalidomide
Adverse effects-- Myelosuppression.
--VENOUS AND ARTERIAL THROMBOEMBOLISM
--muscle cramp/spasms
-- EMBRYO-FETAL TOXICITY
What mutation is associated with loss of response in patients with 5q- MDS treated with lenalidomide
Mutation in TP53
Morphologic features of cells in MDS? Any 3
Ring sideroblasts
Nuclear lobulation
Pseudo-peglar anomaly
Young 28 y/o female presents with intracranial hemorrhage and DIC. Smear reveals blasts many auer rods and atypical promyelocytes. What will you give while waiting for cytogenetics or molecular confirmation?
What mutation would you expect?
--Its APML, Give ATRA, Aggressive DIC supporT
T(15;17)
How do you treat lower risk MDS [ the one with (IPSS low, INT-1) (IPSS-R L) (BM blasts < 10%)
Supportive-
Iron chelation
Growth factors
Luspatercept
HMAs
Lenalidomide (5q-)
Clinical trial
How to you treat normal risk vs high risk APML
low risk ATRA+ATO
High risk ATRA+ATO+ Idarubicin and/or gemtuzumab
MDS classification based on blast %
5%-9% Blasts in Bone Marrow
MDS with increased blasts 1 [MDSIB-1] (WHO 2022)
10-19%
MDS with increased blasts 2 [MDSIB-2] (WHO 2022)
MDS/AML (ICC)
Major adverse effects of ATRA,and ATO (1 each)
ATRA---differentiation syndrome: Treat with DEX 10 mg BID (IV or PO) until resolution
ATO-- Electrolyte imbalance
[Potassium, magnesium , QTC monitoring)
How do you treat hight risk MDS[(IPSS INT-2, high) (IPSS-H) (BM blasts > 10%)]
* Intensive chemotherapy
* HMA (5-AZA/decitabine)
* Clinical trial
followed by
ALLO HSCT
--> Patient ELIGIBLE for intensive chemotherapy and has Core binding factor AML. How do you treat?
--> Is CNS Prophylaxis standarl for AML? If not, who needs it
--Intensive chemo [7 Cytarabine +3 Daunorubicin Induction f/by Consolidation with HiDAC x 3-4 cycles + gemtuzumab
• Not standardized • Some centers administer 1-2 LPs with IT cytarabine once in CR for patients with FLT3+, WBC > 50K, or M4/M5 (monocytic) morphology
Cytogenetics associated with MDS? Any 5
del(5q), del(11q) del(12p) del(20q)
der(3) der(3), double -7/del(7q), Complex: 3 abnormalities--Bad
Patient on Venetoclax was now started on voriconazole for fungal infection. Do you stop ventoclax or decrease/increase the dose?
Venetoclax is metabolized by CYP3A4 and voriconazole is CYP3A4 inhibitor, which can lead to elevated venetoclax levels. Therefore, in the setting of strong CYP3A inhibitors, at least a 75% venetoclax dose reduction is recommended
When do you give EPO analogues? any cutoff for serum EPO levels before it can be given? What is the Hb goal?
-->EPO analogues are an acceptable option for patients with EPO ≤500 mU/mL and/or ≥15% ringed sideroblasts.
--> ESA regimen should be adjusted to maintain the Hb/Hct that is sufficient to avoid RBC transfusions, and maintain oxygen delivery (usually Hb 10 g/dL)
Favourable and Poor Risk AML
Favourable Risk--Core bonding factor leukemias (t(8;21), i16, t(16;16)
- CEBPA-BZIP in-frame mutation
- NPM1 mutations without FLT-ITD.
Intermediate
- FLT 3 ITD (irrespective of NPM1)
- T(9,11)
Poor
Everything else is poor! eg Mutated TP53, ASXL1, t(6;9), t(9;22), -5, -7, -17, inv(3), complex cytogenetics...