Myelodysplastic/Myeloproliferative disorders

Question 1

Overview of Myelodysplastic syndrome

Answer 1

Lots of new cases every year, Men, Elderly, Phenotype is peripheral cytopenias with normal bone marrow, risk to transform to leukemia (AML specifically)

Question 2

What are risk factors for MDS?

Answer 2

Most are unknown cause

Secondary MDS: Genetic factors, Environmental, Antineoplastic drugs

Question 3

What are the signs and symptoms of MDS?

Answer 3

Anemia (Low RBC), Infections (Low Neutrophil), bleeding (Low Platelet), Organomegaly (spleen), Sweet’s Syndrome (red lesions on body)

Question 4

What are the lab features of MDS?

Answer 4

Bone marrow: should be performed if unexplained cytopenia, Trilineage dyspoiesis (excess blasts, abnorm WBC (bilobed neutrophil),RBC (ringed sideroblasts), GIANT platelet)
Peripheral Blood smear: iron studies and cytopenia

Question 5

What are drugs that can cause MDS?

Answer 5

Alkylating agents: longer latency, Produced MDS before progressing to AML, highly resistant to tx.

Topo Inhibitors: 1-2 years latency, progresses straight to AML and skips MDS, highly resistant to tx.

Question 6

What is the International Prognostic Scoring System IPSS?

Answer 6

It rates Marrow percentage of blasts, Karyotype, and Cytopenia to give a number to tell how long the pnt has before progression to AML or to death

Question 7

What is 5q- Syndrome?

Answer 7

It is a MDS entity
Female, 68 years old, Anemic, Low WBC, high platelets
Good prognosis, less chance to progress to AML, only MDS that can be treated with drug Lenalidomide.

Question 8

What is Chronic Myelomonocytic Leukemia (CMML)?

Answer 8

Form of MDS, increased monocytes really high in marrow, variable dysplasia,
Unique: can respond to Imatinib; othewise use azacytidine

Question 9

What is Hypocellular MDS?

Answer 9

Same clinical features as Hypercellular MDS, resembles aplastic anemia,
Tx: immunosuppressive

Question 10

What is the tx for MDS?

Answer 10

Low intensity:
- Supportive (give G-CSF response 70%, EPO)
- transfusion,
- Growth factor to stimulate Hbg
High Intensity:
- Stem cell transplant, - ideally do this in pnts under 40, but most MDL is in 70s. do in people who have lower IPSS score
- chemo, (Hypomethylating agents - azacytidine, Decitabine)
- novel tx

Question 11

Myeloproliferative Disorders

Answer 11

Myeloproliferative Neoplasms: overproduction of one or more cell lines (RBC, WBC, etc), risk for leukemia transformation

Myeloproliferative disorders: 
Chronic Myeloid Leukemia (CML), 
Polycythemia Vera
Essential Thrombocytosis
Primary myelofibrosis

Question 12

What are the Genetic defects associated with Myeloproliferative neoplasms?

Answer 12

Polycythemia Vera: JAK2
Essential Thrombocytosis: JAK2
CML: BCR-ABL

Question 13

CML

Answer 13

Symptoms: fatigue, nightsweats, wt loss, splenomegaly, anemia, platelet dysfunction, HYPERLEUKOCYTOSIS
Labs: Neutrophilia, and immature myeloid cells, basophilia, elevated LDH, Uric acid - risk of tumor lysis syndrome
PHases:
Chronic - most common, we want this, easy tx, BCR-ABL mutation, high ldh,
Accelerated phase: blasts 10%, not enough to be considered leukemia but still a lot, cytopenias unresponsive to therapy
Blast Phase: blood or marrow blasts >20%, technically acute leukemia

Dx: need BCR-ABL mutation, check Marrow to see abnormal size/shape, Confirm dx with FISH or RT-PCR

Tx: imatinib,
Nilotinib (can cause QT prolong), Disatinib (can cause myelosuppression) - second generation tki’s. If in accelerated or blast phase, do these last 2.

Question 14

Polycythemia Vera

Answer 14

Elevated RBC mass in absence of secondary conditions
Inc in WBC and platelets
Male, 60-65, JAK2 mut in 90% pnts
Most likely this if you have elevated Hbg, WBC and platelet count
Symptoms: Pruritis, erythromelalgia (red hands), thrombosis, GI complaints, headache, dizziness, vision change from clogging of capillaires.
Signs: HTN, splenomegaly, hepatomegaly, ulcers, gouty features, pulm HTN

Dx:
Major criteria: Hgb>18.5, presence of JAK2 mut
Minor criteria: Bone marrow with hypercellularity and trilineage growth, Serum EPO below reference
Can have one major and two minor, or one major and two minor.

Tx: Phlebotomy and low dose aspirin,
If high risk individual (>60, hx of emboli): additonal cytoreductive therapy (hydroxyurea)

Question 15

Essential Thrombocytosis

Answer 15

60 yr, women
Jak2 v617f in 40-50%
all elevated cell lines
Marrow shows mainly enlarged megakaryocytes elev. others are elevated, but not enough to be called PV, or other myeloprolif disorder
Platelet count Greater than 450/10^9/L
Secondary cause: any stress on body, splenectomy
Tx: hydroxyurea + ASA.
if failed hydroxyurea - anagrelide, IF-alpha

Question 16

Primary myelofibrosis

Answer 16

Worst prognosis of all these
survival less than 5 yrs
65 yr
Marrow fibrosis and extramedullary hematopoiesis
clinical features: iron overload, fatigue, splenomegaly, Hgb and WBC can be low, Platelet can be high
Tx: palliative and supportive