Schowinsky MDS and MPN Flashcards
Define myelodysplastic syndrome
group of conditions where the marrow is replaced by malignant clone, derived from a tranformed stem or progenitor cell
What are the 2 big characteristic features of MDS
ineffective hematopoiesis and increased risk of tansformation to acute leukemia
Clinical scenario for Primary (idiopathic) MDS
median age of diagnosis 70; usually over 50; 3-5 cases/100k/year
Clinical scenario for Secondary MDS
usually therapy related, occurs as part of spectrum of t-AML, usually diagnosed 2-8 years following therapy with DNA-alkylating agents or ionizing radiation. Contains complex karyotype with whole of partial deletions of chromosomes 5 and/pr 7
T or F: diagnosis of MDS is usually considered when persisten peripheral cytopenia in one or more lineages is present and cannot otherwise be explained
TRUE
T or F: If isolated persistent cytopenia is present, it is usually neutropenia or thrombocytopenia, not anemia
FALSE, other way around
With persistent cytopenia, what 3 modalities can be used to establish MDS
1) morphologic evidence of dysplasia 2) increased myeloblasts, but less that 20% of blood of marrow 3) presence of a clonal cytogenetic abnormality
What percentage of the cells in one lineage (erythroid, granulocytes, megakaryocytes) need appear dysplastic to qualify as dyshematopoiesis
10%
What are some morphologic features to look for dyserythropoiesis (3)
1) Megaloblastoid chromatin patterns in RBC Precursors, 2) Nuclear Irregularities (shape, number, ect.), 3) Prominent ring sideroblasts
What are some morphologic features to look for dysgranulopoiesis (3)
1) hypogranular, 2) megaloblastoid chromatin, 3) Pelgeroid neutrophils (bilobed nuclei)
What are some morphologic features to look for dysmegakaryopoiesis (2)
1) small, 2) hypolobated or non-lobated nuclei
list some common MDS-related abnormalites (4)
1) deletion, whole or partial, of chr 5 and or 7, 2) isolated deletion 5q, 3) trisomy 8 ? and 4) others
Define low grade MDS
myeloblsts account for <2% of blood cells
Define high grade MDS
Myeloblasts account for 5-19% of marrow cells and/or 3-19% of blood cells
T or F: Refractory cytopenia with unilinage dysplasia (RCUD) is a low grade MDS with dysplasia in only one lineage
TRUE
T or F: RCUD mostly has cases of refractory anemia and has a good prognosis
TRUE, median survival is >5 yrs and only 2% of cases transform to AML by year 5
T or F: Refractory cytopenia with multilineage dysplasia (RCMD) is a low grade MDS with dysplasia in only one lineage
TRUE
T or F: RCMD has a better prognosis than RCUD
FALSE, median survival is 2.5 yrs and 10% of cases turn to AML
What are the 2 types of high grade MDS?
Refractory Anemia with Excess Blasts-1 (RAEB-1) and Refractory Anemia with Excess Blasts-2 (RAEB-2)
Give some features of RAEB-1
5-9% blasts in marrow, and/or 2-4% blasts in blood, dismal prognosis, median 16 mon survival, 25% of cases will transform to AML
Give some features of RAEB-2
10-19% blasts in marrow, and/or 5-19% blasts in blood, very dismal prognosis, median 9 mon survival, 33% of cases will transform to AML
list 4 secondary myelodysplasias that can mimic MDS
1) vitamin deficiency (B12, folate, etc), 2) Toxin exposure (heavy metals), 3) exposure to certain drugs 4) viral infections
Define Myeloproliferative neoplasms
MPN, clonal hematopoietic neoplasm arising from hematopoietic stem cell.
T or F: MPN is seen in children most often
FALSE
T or F: MPN has clones replacing normal marrow cells in multiple lineages and gives rise to increased numbers of normal blood cells in one or more linages
TRUE, and blood cells are usually not dysplastic
what are some common themes in MPN (4)
1) increased # in blood cell type/s 2) increase in marrow cellularity 3) splenomegaly and/or hepatomegaly 4) insidious onset
If MPN is untreated, what doe it progress to?
excessive marrow fibrosis with resultant bone marrow failue and transformation to acute leukemia
T or F: MPN transformation to acute leukemia is higher than it is for MDS
FALSE
What is chronic myelogenous leukemia (CML)?
MPN, manifests primarily as persistent neutrophilic leukocytosis, presence of BCR-ABL1 gene fusion
clinical findings in CML
non-specific signs/symptoms like night sweats, weight loss, splenomegaly, and anemia. Minority are asymptomatic
What is the typical age of diagnosis for CML?
40-60
T or F: initial phase of CML is the chronic phase and it is when the majority of diagnoses are made
TRUE
Chronic phase of CML is characterized by what?
usually stable, prominent leukocytosis due to neutrophilia, increased basophils, increased platlets, hypercellular bone marrow with prominent granulocytic hyperplasia
What is the blast phase of CML and how does it come about?
If untreated, you get 20% or more blasts in the marrow or blood
What is more common in CML-blast phase, more myeloblasts or lymphoblasts?
myeloblasts
T or F: CML can go directly from chronic phase to blast phase, or go through an intermediate accelerated phase
TRUE
What is the Philadelphia chromosome
BCR-ABL fusion gene. Translocation t(9;22)
Whats the difference between BCR-ABL in CML cs Ph+ ALL
presence of p210 fusion protein, though some p190 may be found
What do we treat CML with
protein tyrosine kinase inhibitors (PTLIs) such as GLEEVAC
Why come we need 2nd and 3rd gen PTKIs?
some patients with CML develop resistance to imatinib (gleevac) through mutations
What is polycythemia vera (PV)
MPN characterized by an increase in RBC mass
What other findings can apear in PV
increased neutrophils and platelets in blood, trilineage hyperplasia in marrow, and bizarre megakaryocytes in marrow
What do most all cases of PV have cytogenetically?
activating mutation of JAK2, usually V617F mutation
If a patient has persistent erythocytosis w/o demonstrable JAK2 mutation, what secondary erythrocytosis causes should you expect?
smokers (due to carboxyhemoglobin), chronic hypoxia, certain hemoglobin disorders
when is PV usually dianosed?
polycythemic phase with increased blood cell counts
What does PV progress to
spent phase (aka post-PV myelofibrosis), with extensive marrow fibrosis and a fall in blood cell count
What are clinical presenting symptoms of PV
headaches, dizziness, plethora (dusky, reddish skin), pruritus (itchy), paresthesia (pin and needle sensation), splenomegaly (70%), hepatomegaly (40%)
What are the most serious complications of PV
venous and arterial thrombosis leading to DVT, MI, or stroke
Thrombosis of what should raise suspicion of PV
mesenteric vein, portal vein, or splenic vein
T or F: PV has a good prognosis
TRUE, survival times are 10-20 years
What are the main therapeutics of PV
serial phlebotomy and aspirin therapy
What do you give for problematic symptoms of PV and what can it cause?
mild chemotherapy, but this increases risk of transformation to acute leukemia
What is Primary myelofibrosis
PMF is an MPN characterized by granulocytic and megakaryocytic hyperplasia, but no erythrocytosis.
T or F: JAK2 mutations are never seen in PMF
FALSE, seen in 50% of cases
What stage does PMF start in?
prefibrotic stage, which has increased platelets, increased neutrophils, hypercellular marrow, and granulocytic and megakaryocytic hyperplasia
What does the fibrotic stage of PMF see
reticulin fibrosis in marrow, leukoerythroblastosis in blood, falling blood cell counts, extramedullary hematopoiesis leading to organomegaly
what histologic features are seen in PMF fibrotic stage
immature granulocyts and red cells in blood, darcocytes (tear drops RBC), streaming appearance of marrow and bizarre entrapped megakaryocytes
what is prognosis of PMF
not great. Most deaths due to bone marrow failure, minority become AML, survival if diagnosed in fibotic stage is 5 years
what is Essential thrombocythemia
ET is an MPN characterized by persistent thrombocytosis, lacks marrow granulocytic hyperplasia, atypical megakaryocytes in ET are even larger than PMF.
T or F: JAK2 mutations are present in 50% of ET cases
TRUE
If present, what are some signs and symptoms of ET
transient ischemic attacks (TIAs), digital ischemia, arterial and venous thrombosis (less common than PV)
T or F: Splenomegaly is common in Et
FALSE
What is the prognosis of ET?
good, indolent disease with survivals of over 10 years, and transformation to myelofibrosis or AML is rare
T or F: if asymptomatic, ET is diagnosed with CBC results
TRUE
