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MALIGNANT HEME > SET9 > Flashcards

SET9 Flashcards

1
Q

What kind of “CML” is Ruxolitinib useful in and why?

A

CNL (Chronic Neutrophilic Leukemia) in which most have CSF3R mutations leading to preferential downstream kinase signalling though SRC family-TNK i.e. JAK kinases so Ruxolitinib useful here

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2
Q

What is the treatment for Indolent Mastocytosis?

A

Cromolyn, H1/H2 blockers and topical steroids

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3
Q

What kind of Essential thrombocytosis has the shortest survival? Longest?

A

ET w/ MLP515+; longest are those who have triple negative ET which is negative for JAK2, CALR, and MLP515

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4
Q

Low Risk MDS w/ 5q del can be treated with what?

A

Lenalidomide 10 mg PO daily

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5
Q

What are the 5 points used for a Prognostic Scoring system for Primary Myelofibrosis?

A

Age >65, presence of consitutional sx, Hgb less than 10, Leukocyte count >25k, and circulating blast count >1% (0 - low risk, 1 - intermediate1, 2 -intermediate2, 3 or more - high risk)

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6
Q

What lymphoma will often have cytoplasmic staining + for BCL-2?

A

Follicular Lymphoma because t(14;18) leads to BCL2 overexpression

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7
Q

What C-kit mutation in Systemic Mastocytosis precludes use of imatinib (usually DOC for C-kit mutations)

A

C-kit with D816V

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8
Q

In what type of MDS is lenalidomide used?

A

Transfusion dependent low or intermediate risk MDS w/ del 5q; if concomittant del7q that is a poor risk factor and probably would not give lenalidomide

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9
Q

What is the typical EPO level in patients with congenital erythrocytosis? Which one has the opposite?

A

Usually low except in Chuvash Polycythemia (which is normal to high and due to abnormalities of O2 signalling)

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10
Q

What is Pacritinib?

A

A newer JAK2 inhibitor that can be used regardless of platelet count as Ruxolitinib often only good if platelet count >50k and usually pts with PMF have cytopenias due to BM fibrosis

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11
Q

What was evaluated in the COMFORT-1 and COMFORT-2 trials?

A

That JAK2 inhibitors where useful for decreasing B symptoms of Primary Myelofibrosis as well as for treating painful splenomegaly (also increase PFS and OS)

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12
Q

FIP1L1/PDGFRA fusion protein is the most common mutation in _________ and is also commonly seen in __________

A

Hypereosinophilic Syndromes; Systemic Mastocytosis (however, in mastocytosis the most common gene is C-kit)

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13
Q

What are 4 features in Hypoplastic MDS that predict for good response to immunsuppressive tx (i.e. ATG and cyclosporine)?

A

Age <60, hypocellular marrow, HLA-DR15+ and PNH clone +

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14
Q

Patients with Myeloproliferative Neoplasms can have JAK2 or CALR positivity (there are others) but which is assoc with decreased risk of thrombosis and improved OS?

A

CALR (encodes Calreticulin) decreased risk of thrombosis

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15
Q

How would you tx a pt with ET if their platelet count was >1 million but pt was 50 and had no evidence of thrombosis or personal hx of thrombosis

A

Aspirin alone; High risk ET is based on age>60 and personal hx of clot alone regardless of platelet count

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16
Q

What is the optimal hematocrit in JAK2 Polycythemia Vera?

A

45 (~hgb 15)

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17
Q

What should you send for if there is concern for Polycythemia vera but JAK2 V617F is negative?

A

Send for JAK2 exon 12 mutation analysis

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18
Q

What is CALR and what is the significance in patients with Myeloproliferative Disorders?

A

CALR encodes Calreticulin and patients with this mutation have more favorable prognosis than those w/ JAK2 mutations (this is discussed more so in ET and PMF than PV)

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19
Q

What two mutations in Systemic Mastocytosis can have response to Imatinib?

A

C-kit mutation (MC) as well as FIP1L1-PDGFRA fusion protein; HOWEVER, if C-kit w/ D816V present imatinib not useful

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20
Q

What is the most common mutation seen in Hypereosinophilic Syndrome? What other one can be seen?

A

FIP1L1/PDGFRA (fusion protein) and Imatinib can be useful here; ALSO some have 5q33 translocation leading to PDGFRB and also respond to Imatinib just like CMML

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21
Q

How does WHO define RAEB-1 and RAEB-2?

A

RAEB-1 is MDS w/ 5-9% blasts; RAEB-2 is MDS w/ 10-19% blasts

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22
Q

Bone loss (on DEXA), diarrhea and flushing with elevated tryptase suggests what

A

Systemic Mastocytosis (often C-kit mutation sometimes FIP1L1/PDGFRA); BM flow CD117+ CD25+; responsive to Imatinib unless C-kit D816V

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23
Q

How does Follicular lymphoma usually present?

A

Multistation Lymphadenopathy, BM involvement (paratrabecular infiltrates) and splenomegaly- i.e. Ann Arbor Stage IV

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24
Q

Androgen creams may result in what finding on CBC?

A

Erythrocytosis as does being s/p renal xplant

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25
Q

When should you consider chelation therapy in patients with transfusion-dependent MDS?

A

If ferritin >1000

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26
Q

What defines a person as having high risk Essential Thrombocytosis? Tx?

A

Age >60 OR personal hx of blood clots; Hydroxyurea AND Aspirin

27
Q

The underlying mutation in Systemic Mastocytosis is often C-kit but can also be _______. Also seen in?

A

FIP1L1/PDGFRA; Hypereosinophilic Syndromes

28
Q

What are the 3 possible mutations for Essential Thrombocytosis that are typically though of? What is the deal with “Triple Negative ET”?

A

JAK2, CALR, and MLP515; triple negative ET has the longest survival and lowest incidence of recurrent thrombosis

29
Q

Erythromelalgia and Aquatic Pruritis are common sx of this

A

Polycythemia Vera

30
Q

CSF3R mutations underly 90% of this hematologic malignancy

A

Chronic Neutrophilic Leukemia (atypical CML)- sometimes called CNL

31
Q

What is CNL?

A

Chronic Neutrophilic Leukemia (atypical CML); >90% have CSF3R mutation; this mutation leads to increased signaling through JAK and so Ruxolitinib useful

32
Q

At what lifetime # of tranfusions should you suspect someone probably has some degree of iron overload?

A

20-40 transfusions; start monitoring ferritin at this point

33
Q

What is the use of Ruxolitinib in Polycythemia vera?

A

Can be used for patients who either had inadequate reponse to or could not tolerate Hydroxyurea; has been shown to decrease splenomegaly and need for phlebotomy

34
Q

What medication can help to resolve an erythrocytosis in a patient who is s/p renal transplant?

A

ACE-inhibitors due to the deregulated Renin-Angiotensin-Aldosterone axis

35
Q

What is a potential issue in giving Ruxolitinib in patients with Primary Myelofibrosis?

A

It can cause thrombocytopenia and should not be given in patients with platelet count <50k which is common in PMF as it leads to cytopenia, use Pacritinib instead

36
Q

How is the starting dose of Ruxolitinib decided?

A

20 mg PO bid if platelet count >200k, 15 mg BID if platelet count 100-200 and not used if <50k would then need Pacritinib instead

37
Q

Hypoplastic MDS often has overexpression of what and is treated how?

A

HLA-DR2 and its serologic split HLA-DR15 and a study showed a statistical significance in pts with HLA-DR15 to anti-thymocyte globulin and cyclosporine

38
Q

What mutations underly Chronic Neutrophilic Leukemia (atypical CML)?

A

CSF3R

39
Q

T/F: Ruxolitinib (a JAK2 inhibitor) only works in primary myelofibrosis if there is JAK2 positivity

A

False can be given in PM whether there is JAK2 positivity or NOT; this is because the JAK-STAT pathway is STILL INVOLVED in cell division!

40
Q

Explain the difference in using imatinib to tx CMML vs. CML

A

In CML imatinib has activity against BCR-ABL which is a tyrosine kinase; in CMML imatinib has activity against PDGFR-B which is also a tyr kinase; CMML has nothing to do with BCR-ABL

41
Q

What does the data show with respect to interruption of hypomethylating agents in a patient who is responding w/ MDS?

A

Associated with relapse and poor prognosis

42
Q

What are the two possible mutations for Polycythemia vera?

A

JAK2 V617F and JAK2 Exon 12

43
Q

What happens with the V617F mutation in PV?

A

A phenylalanine is switched for valine at position 617 in the JAK2 gene

44
Q

What is the IHC of follicular lymphoma?

A

CD19+, CD20+, and CD23+ often with cytoplasmic expression of BCL2

45
Q

Bone Marrow flow cytometry of Systemic Mastocytosis often shows what

A

CD117+ and CD25+

46
Q

What percent of Essential Thrombocytosis is JAK2+?

A

50%

47
Q

MDS-RA (w/ ringed sideroblasts) is classically not very responsive to what?

A

ESA’s but can show some improvement with G-CSF

48
Q

Patients who are s/p renal transplant may have what finding on CBC?

A

Erythrocytosis as do androgen creams

49
Q

Explain the molecular similarity of CMML and Hypereosinophilic Syndrome

A

CMML often has activation of PDGFRB due to 5q33 translocation and is treated with Imatinib; Most Hypereosinophilic Syndromes have the fusion tyrosine kinase FIP1L1/PDGFRA and Imatinib can also be used here; however, they often ALSO have 5q33 translocation leading to PDGFRB just like CMML and imatinib also used here

50
Q

What can you say, from a prognosis standpoint about MDS w/ 5q del and one with 7q del?

A

5q del is a good prognostic indicator and has robust response to lenalidomide 10 mg PO daily; 7q is a poor prognostic finding

51
Q

What are the indications for JAK2 inhibitors (Ruxolitinib) in Primary Myelofibrosis

A

Consitutional B symptoms and in cases of painful splenomegaly or symptomatic splenomegaly (early satiety); it does also increase PFS and OS

52
Q

What is the minimal platelet count for which you can give Ruxolitinib?

A

50,000 as it causes thrombocytopenia so should not be given if platelet count lower

53
Q

Typically AML is defined by having greater than 20% blasts but what cytogenetic features also define it as AML even if blast count is lower?

A

t(8;21), t(15;17) and inv(16)

54
Q

PDGFR-B activation in CMML is due to mutations on what gene?

A

5q33, esp t(5;12)- can be tx with imatinib as PDGFR-B is a tyrosine kinase

55
Q

What are often the sx of Systemic Mastocytosis?

A

Bone loss, diarrhea and flushing with elevated tryptase

56
Q

If a pt w/ low risk MDS w/ 5q del was on lenalidomide progresses to high risk what do you do?

A

DC the lenalidomide and treat as a normal high risk MDS w/ chemo or azacitadine (if elderly) w/ allo-HSCT or reduced-intensity allo-HSCT

57
Q

What is Chuvash Polycythemia?

A

An Autosomal Recessive disorder of erythrocytosis due to abnormalities of oxygen signaling (has a normal to high EPO, most congenital erythrocytoses have low) and was first discovered in the Chuvash region of Russia

58
Q

What kind of sx can Primary Myelofibrosis cause?

A

Cytopenias with B symptoms and JAK2 inhibitors are useful to treat BOTH the constitutional sx AND the splenomegaly

59
Q

How do you make a diagnosis of Hypereosinophilic syndrome?

A

Needs to be Eosinophilia >1500 at least for 6 months and all other causes ruled out (allergy, parasite) and there should be organ involvement often neurologic or endomyocardial fibrosis are the fatal ones

60
Q

What did the PERSIST trial show?

A

That Pacritinib which is a newer JAK2 inhibitor can be used in PMF w/ platelet count <50k

61
Q

At what CrCl should Defirasirox not be given?

A

CrCl <40

62
Q

What myeloproliferative disorder often has PDGFR-B activation and can look like CML?

A

CMML- it has activation of PDGFR-B which encodes a tyrosine kinase, the gene is on 5q33 and t(5;12) in particular leads to its activation and can be Tx w/ imatinib which also affects this tyr kinase

63
Q

What is the definition of Systemic Mastocytosis?

A

Abnormal proliferation of Mast Cells in 1 or more organs (often C-kit +)

64
Q

Neurologic involvement and Endomyocardial fibrosis are often seen in what hematologic disorder of granulocytes?

A

Hypereosinophilic Syndromes (eos are granulocytes)

MALIGNANT HEME (12 decks)

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