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67 Cards in this Set
- Front
- Back
What are causes of pancytopenia?
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Aplastic anemia
Myelodysplastic syndromes Bone marrow infiltration' Nutritional deficiencies Bone marrow toxins Infections Hypersplenism Systemic disorders Anorexia |
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What are some bone marrow infiltrates that can cause pancytopenia?
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Leukemia
Lymphoma Carcinoma Granulomatous disease Fibrosis Congenital storage disease |
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What are some nutritional deficiencies taht can cause pancytopenia?
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B12
Folic acid |
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What are some bone marrow toxins that can cause pancytopenia?
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Chemo
Radiation Chemical exposure Alcohol |
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What are some infections that can cause pancytopenia?
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HIV
EBV Parvovirus Hepatitis Histoplasmosis Tb |
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What is the definition of aplastic anemia?
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Peripheral blood pancytopenia
Bone marrow hypocellularity |
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When can AA occur?
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Any age!
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What are causes of acquired AA?
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Acquired (vs. inherited) are 80% of the AA cases
Of those: Idiopathic (50%) Also: Meds Toxins Viruses Immune disorders Others |
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What are some meds that can cause acquired AA?
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Chloramphenicol
Gold Sulfonamides NSAIDs Arsenic Antiepileptics Clopidogrel |
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What are some toxins that can cause acquired AA?
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Benzene
Alcohol Chemo Radiation |
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What are some viral infections that can cause acquired AA?
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EBV
Non-A, B, C hepatitis HIV Parvovirus B19 |
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What are some immune disorders that can cause acquired AA?
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SLE
Transfusion associated graft vs. host disease Eosinophilic fascitis |
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What are some other causes of acquired AA?
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Paroxysmal nocturnal hemoglobinuria
Thymoma Pregnancy |
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What are the characteristics of inherited AAs?
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In the context of other symptoms
Early onset |
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What's the clinical presentation of AA?
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Anemia:
Neutropenia Thrombocytopenia |
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What are some of the signs and symptoms of anemia?
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Pallor
Fatigue Chest pain SOB Headache |
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What are some of the symptoms of neutropenia?
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Fever
Infections |
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What are some of the symptoms of thrombocytopenia?
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Bruising
Petechiae Epistaxis Gingival bleeding Menorrhagia |
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What labs should you order in the context of aplastic anemia?
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CBC
Reticulocyte count (is the bone marrow working?) Bone marrow biopsy: look for the hypocellularity Work them up to look for other potential causes |
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Take a look at this:
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In AA, there is essentially NOTHING in the marrow.
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What are the grades of AA?
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Nonsevere: <30% marrow cellularity; absence of pancytopenia
Severe: Marrow < 25% OR <50% with few hematopoietic cells and pancytopenic signs Very severe: see severe, but with ANC <.2E9 |
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What's the pathogenesis of aplastic anemia?
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Damage/destruction/suppression of the hematopoietic stem cell leads to a depletion of the stem cell pool-->marrow failure-->AA
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What are the mechanisms by which the pathogenesis of AA can happen?
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Direct toxic effects to the hematopoietic stem cells
Immune mediated suppression of the hematopoietic stem cell |
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What's the supportive treatment for AA?
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Supportive care:
-Transfusions -Iron chelating agents -Antibiotics -Growth factor support: GCSF, EPO |
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What's the curative treatment for AA?
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Hematopoietic stem cell transplantation
Immunosuppressants |
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What ages do you do a hematopoietic stem cell transplant for if they have AA?
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Under 45.
Try and get a matched sibling donor; otherwise you can use an unmatched. |
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What's the prophylaxis used for GvHD in allogenic hematopoietic stem cell transpant (HSCT)?
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Methotrexate/cyclosporine
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What are the meds that you give to someone before a HSCT to prepare them?
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Cyclophosphamite
Antithymocyte globulin HSC infusion |
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What's the prognosis for someone who gets a HSCT with AA?
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88% survival at 8 years
32% with chronic GvHD 4% graft failure |
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What are the complications following HSCT?
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Graft failure
GvHD (more common with unrelated donors) Malignancy |
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What are some complications to the immunosuppression for HSCT to cure AA?
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Serum sickness
Renal failure HTN Late malignancies (MDS/AML) |
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How long after HSCT does it take to see a response?
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3-4 months
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What cells go awry in myelodysplastic syndrome?
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Clonal hematopoietic stem cells
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What are the findings in myelodysplastic syndrome?
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Peripheral blood cytopenias
Hyperplastic (uaully) bone marrow with dysplasia |
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What are the symptoms found in myelodysplastic syndrome?
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Anemia
Neutropenic symptoms Thrombocytopenic hemorrhage, easy bruising Symptomatic organomegaly/LAD Bone/joint pains Weight loss Night sweats No lymphadenopathy |
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What are some of the findings in the RBCs in myelodysplastic syndromes?
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Macrocytic
Nucleated RBCs Poikilocytosis: abnormally shaped RBCs Anisolytosis: variance in size |
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What are some WBC findings in myelodysplastic syndromes?
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Pelger-Huet neutrophils; neutrophils whose nuclei are hyposegmeneted
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What is the hallmark of myelodysplastic syndrome in the RBC precursor in bone marrow?
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Megaloblastic maturation in RBC precursors: the nuclei and the cytoplasm mature at different rates; nuclei lags behind
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What are the pathologic changes in megakaryocyte development in the bone marrow in myelodysplastic syndrome?
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Multiple separate nuclei
Unilobate megakaryocytes (instead of many-lobed) Small platelets |
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Cytogenetically, how do you differentiate between myelodysplastic syndrome and aplastic anemia?
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MDS: typically show more chrosomal abnormalities
Commonly deletions/duplications; lack of translocations -Some are better than others; some are worse |
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When does myeloblastic syndrome typically occur?
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It starts showing up at around 60, peaks at 75-85
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What are some important concepts underlying myelodysplastic syndrome classification?
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Cell morphology
Blast percentage in the peripheral blood/marrow Cytogenetic information Different subtypes give a different prognosis |
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What's the international prognosis scoring system?
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Commonly used scoring system for MDS.
Based on blast percentage, cytopenias, and karyotype information |
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People who have a higher IPSS scores show what findings?
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Less survival
More progression to AML |
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What are common causes of therapy-related MDS?
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Alkylating agents
Radiation exposure |
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What conditions are associated with alkylating agents and radiation exposure? How long do these take to develop?
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MDS
AML 5-7 years |
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What are the changes that happen in therapy-related MDS?
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Deletion/loss of chromosome 5 and/or 7
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What's the prognosis for therapy-related MDS?
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Very poor; they're going to die.
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What are the findings in chronic myelomonocytic leukemia?
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Peripheral blood:
-Absolute monocytosis > 1E9 -BCR/ABL negative -< 20% blasts Bone marrow: -Dysplasia in 1 or more lineages - < 20% blasts |
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What is 5q clinical syndrome?
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Happens to females
70 years old Isolated macrocytic anemia; quiet. |
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What is the prognosis for 5q clinical syndrome?
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Great!
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What are the cellular findings in 5q clinical syndrome?
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Normal-elevated platelet counts
bone marrow erythroid hyperplasia Hypolobulated megakaryocytes |
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What are the treatments for MDS?
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Observation
Allogenic HSCT (too old, usually!) Intensive chemotherapy Supportive care/hematopoietic growth factors Immunosuppression DNA methyltransferase inhibitors IMiDs (antiapoptosis agents) Clinical trials |
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How do you minimize transfusions in myelodysplastic syndrome?
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Erythropoiesis stimulating agents
A certain subset are more likely to respond -Low endogenous EPO -Low existing transfusion requirements -Bone marrow blasts <10% |
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What's the use of chelation therapy in MDS?
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Remove the iron from MDS patients who are being transfused often
Only used in patients who have a long life expectancy, anyways. |
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What are some hypomethylating agents used in MDS?
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Azacitidine
Decitabine |
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How do the hypomethylating agents work in MDS treatment?
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Stop methylation of the chromosome --> allow transcription of important genes
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What are indications for hypomethylating agents?
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Transfusion dependence
Neutropenic Systemic symptoms Large blast burden |
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What are the results of using hypomethyating agents in MDS?
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50% response rate
Just prolongs life, increases quality of life |
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What are the toxicities of the hypomethylating agents?
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Infection risk
Suppression of the marrow Renal, liver toxicity |
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What are indications for the immunomodulatory agents in MDS?
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Severe disease
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What are the special uses for immunomodulatory agents in MDS?
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5q deletion (think the old ladies with the indolent course) --> this is very good for them!!!
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What are the responses to the immunomodulatory agents?
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50%
Prolong life; decrease transformation to AML |
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What is the response to some of the hypomethylating drugs?
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Very slow. You need to give the drug in 3-4 month cycles to assess responses.
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What are the hypomethylating agents for MDS?
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Azacitidine
Decitabine |
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What are some of the the non-curative agents for myelodysplastic syndrome?
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DNA methltransferase inhibitors
Immunomodulatory agents Chelating agents EPO stimulators All help with the symptoms secondary to MDS |
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If someone has MDS, what should you do?
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Recommend them for a clinical trial!
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