EXAM #3: MDS/MPD Flashcards
What is MDS? What are the general characteristics of MDS?
MDS= Myelodysplastic Syndrome
- Dysplasia or bad growth of the bone marrow cells
- Increased number of cells i.e. hypercellular bone marrow with poor products
- Results in various cytopenias (low numbers)
- Blasts less than 20% in the bone marrow
Greater than 20% blasts= leukemia*
What is the major etiology of MDS?
Most myelodysplasias result from de novo mutations
What causes secondary MDS?
- Genetic factors
- Environmental factors
- Antineoplastic drugs
What are the signs and symptoms of MDS?
- Anemia
- Infection
- Bleeding
- Organomegaly/ Lymphadenopathy
- Sweet’s Syndrome
What is Sweet’s Syndrome?
Acute febrile neutrophilic dermatosis
How is MDS diagnosed?
Bone marrow biopsy
PBS
What are some of the cell types seen on PBS that are typical of MDS?
1) Giant platelets
2) Pseudo-Pegler Huet anomaly
3) Ringed Sideroblasts
List the differential diagnoses of MDS.
- Vitamin B12 and Folate Deficiency
- Viral infection e.g. HIV
- Chemotherapy
- Alcohol
- Lead toxicity
- Benzene
- Erythropoietic agents e.g. EPO or G-CSF
What types of chemotherapeutic agents cause MDS?
- Alkylating agents
- Topoisomerase inhibitors
Which class of chemotheraputic drugs can more quickly cause lead to MDS?
Topoisomerase inhibitors
Which class of chemotheraputic drugs more commonly leads to MDS?
Alkylating agents
What is 5q-Syndrome? What patient population is this seen in?
Subtype of MDS that causes:
- Macrocytic anemia
- Luekopenia
- Platelet counts elevated
This is seen in FEMALES
What is the prognosis for 5q Syndrome?
Good
What drug is used to treat 5q Syndrome?
Lenalidomide
What is CMML?
Chronic Myelomonocytic Leukemia
What are the characteristics of CMML?
- Increased monocytes
- Variable degrees of dysplasia
What drugs can be used to treat CMML?
Imatinib
Azaytidine
What is hypocellular MDS?
MDS with clinical features that resemble aplastic anemia
What is low intensity treatment for MDS?
- Supportive care
- Transfusion
- Growth factor support
What is high intensity treatment for MDS?
- Stem cell transplant
- Chemotherapy
- Clinical trials
What are the “growth factors” that are used to treat MDS?
G-CSF
GM-CSF
EPO
When does EPO tend to work better in patients with MDS?
When EPO level is already less than 500
In patients with MDS, what class of drugs have been shown to decrease time to leukemia and transfusion dependence?
Hypomethylating agents i.e. Azacytidine
What is the role of transplant in the treatment of MDS? What type of transplant is curative?
Allogeneic transplant is curative; however, patients have to be less than 40
What is a myeloproliferative disorder?
Overproduction of one or more blood cell line
What are the classic myeloproliferative disorders?
1) Chronic myeloid leukemia
2) Polycythemia vera
3) Essential thrombocytosis
4) Primary myelofibrosis
What mutation is seen with PV and ET?
JAK2
What is the mutation seen in CML?
t(9:22) BCR-ABL
What are the symptoms of CML?
Fatigue Night sweats Weight loss Splenomegaly Anemia Platelet dysfunction
What are the labs that are characteristic of CML?
1) BASOPHILIA
2) Leukocytosis
3) Neutrophilia
What are the three phases of CML?
Chronic
Accelerated
Blast
What are the characteristics of the chronic phase of CML?
Basophilia
Blasts less than 10
BCR-ABL
What is the hallmark of the acclerated phase of CML?
Worsened splenomegaly
What is the blast phase of CML?
Greater than 20% blasts i.e. transformation to Leukemia
How is CML diangosed?
1) BCR-ABL
2) Basophilia
3) Confirm with FISH or RT-BCR
What is the primary treatment for CML? What class of drug is this?
Imatinib, a tyrosine kinase inhibitor
What is the second line treatment for CML when patients are resistant to Imatinib?
Dasatinib
What causes resistance to Imatinib?
Mutations in the ABL kinase domain
What is Polycythemia Vera?
Elevated RBC mass with concomitant increase in WBC and platelets
What are the symptoms associated with PV?
1) Puritis, especially after bathing
2) Headache
3) Blurry vision
4) Venous thrombosis–>Budd Chiari
What are the major diagnostic criteria for PV?
- High Hb with JAK2 mutation
- 18.5 in men, and 16.5 women
What are the minor criteria for PV?
- Bone marrow hypercellulatiry
- Low serum EPO
What does diagnosis of PV require?
- BOTH major and 1 minor
- 1 major and BOTH minor
What is the first line treatment for PV?
Phlebotomy and low dose ASA
For patients with PV and intermediate risk/ high risk, what is the second line treatment?
Cytoreductive therapy i.e. hydroxyurea
When is hydroxurea contraindicated?
Pregnancy
What is Essential Thrombocytosis?
Isolated increased in platelet count
What are the clinical features of ET?
- Visual disturbance
- Dizziness
- HA
- Erythromelalgia
- Cutaneous ulcers
- Thrombosis (venous or arterial)
- Hemorrhage
What are the diagnostic criteria for ET?
1) Platelet count greater than 450,000
2) BM biopsy with proliferation of megakaryocytic lineage
3) JAK2 mutation or ruled out reactive thrombocytosis
What are the cause of secondary thrombocytosis?
Iron deficiency Infection Inflammation Surgery Trauma Tissue injury/infarction Malignancy S/p splenectomy
How is ET treated?
Hydroxyurea–first line
Anagrelide
What is Primary Myelofibrosis?
Proliferation of mature myeloid cells i.e. megakaryoctes that produce PDGF, causing bone marrow fibrosis
What is the worst of the myeloproliferative disorders?
Primary myelofibrosis
What are the hallmarks of Primary Myelofibrosis?
- Bone marrow fibrosis
- Extramedullary hematopoesis
What are the clinical features of Primary Myelofibrosis?
Splenogmegaly
How is Primary Myelofibrosis treated?
Palliation and support
What are the supportive measures that are commonly undertaken in Primary Myelofibrosis?
1) Recombinant EPO
2) Iron chelation
3) Splenectomy
4) JAK2
5) Allo SCT
