Diagnosis
Requires Bone Marrow Biopsy for diagnosis
Myelofibrosis
JAK2V617F
MF drug being studied in patients with low platelet count
Pacritinib
an oral kinase inhibitor with specificity to JAK2, IRAK1, CSF1R
PERSIST1, PERSIST2 and PACIFICA - PDUFA date November 30, 2021
high risk MF with plt count 120,000 and hgb 9.0, spleen palpable 13cm below LCM what is the starting dose
15mg BID
slurred speech, asymmetrical facial expressions, weakness
Cerbrovascular Accident (CVA) or Stroke
Blood supply to the brain is impeded or cut off
What year was the diagnostic criteria changed in PV
2016
Now recommends BM bx, excluded red cell mass study
Associated with younger age, higher platelet count, more favorable survival
CALR mutation
Being studied in MF, small molecule that targets BCL-XL/BCL2
Navitoclax
In Comfort I what dose of jakafi was required to achieve at least a 30% decrease in spleen volume
15mg or higher
Hydroxyurea intolerance
Platelet count 600; Jak2, CALR, MPL negative; BCR ABL negative; marrow normal with trilineage hematopoiesis no fibrosis; ferritin 4
Reactive thrombocytosis secondary to iron deficiency
Sent to hematology for elevated plt count, r/o ET
When mutations do not coexist, they are
Mutually Exclusive
Approved for PV in Europe, PDUFA date in the US November 13, 2021
Ropeginterferon-alpha 2b
PROUD-PV and CONTINUATION-PV - Thrombotic risk reduction and high rates of CHR and Complete Molecular Response
SQ once every 2 week dosing
In Comfort I 58% of patients had Grade3/4 thrombocytopenia or anemia but what percent had to d/c Jakafi due to thrombocytopenia or anemia
<1%
When platelet counts rise and consume clotting factors patients can experience bleeding
Acquired von Willebrand Disease
New dx MF:
66yr old, WBC 30,000, hgb 9.0, 4% peripheral blood blasts with wt loss, fever and night sweats. What is his median survival
DIPSS score 6, high risk group, 1.5yr median survival
Mutation of the thrombopoietin receptor otherwise known as
MPL
Studied in PV patients to reduce phlebotomy requirements. Mimics hepcidin.
Rusfertide
given weekly SQ
reduces iron availability and decreases erythropoiesis
PV patient on Jakafi 10 mg BID x 6 weeks still requires phlebotomy and has itching
MPN-BP
Persistent (>3months) peripheral blood monocytosis, blast <20%, presence of bone marrow dysplasia
CMML - Chronic myelomonocytic leukemia
Can be further classified as "proliferative" MPN-CMML or "dysplastic" MDS-CMML
Not specific to MPN's but seen also in AML and MDS, this loss of function mutation is found in about 10% of MPN's
TET2
BET inhibitor being studied alone or in combo with JAK inhibitor to reduce spleen size, improve symptoms and has even show anemia improvement as well as decrease marrow fibrosis
Pelabresib
MANIFEST trial
Another Jak inhibitor used in RA was found to have increased risk of what, name 2 of the 3.
MACE - Major Cardiovascular Events
Thrombosis
Secondary Malignancy
Condition in which the hepatic veins are blocked or narrowed by a clot. This blockage causes blood to back up to the liver and the liver enlarges. The spleen may enlarge as well.
Budd Chiari Syndrome