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Flashcards in Exam 4 Deck (46)
1

List 7 learning objectives for Hematopoietic Stem Cell Transplantation (7)

1. Describe purposes of stem cell transplant
2. Understand myeloablative vs. nonmyeloablative
3. characteristics of chemo in conditioning
4. explain role of immunosuppressants
5. describe appropriate monitoring plan for patient on immunosuppressants
6. describe the supportive care measures used in stem cell transplant patients
7. create a treatment plan for a patient with acute graft versus host disease

2

List 1 granulocyte colony stimulating factor (G-CSF) and three (3) side effects

Filgrastim (1) bone pain (2) n/v (3) infusion-related

3

List 1 granulocyte-macrophage colony stimulating factor (GM-CSF) and seven (7) side effects

Sargramostim (1) n/v (2) diarrhea (3) fever (4) skin reaction (5) infusion-related reaction (6) hypertension (7) edema

4

List 1 CXCR4 chemokine inhibitor and 3 (3) side effects

Plerixafor (1) nausea (2) diarrhea (3) injection site reaction

5

List three (3) components of conditioning regimens

(1) chemotherapy; myeloablative or non (2) total body irradiation (3) immunosuppressants

6

List six (6) chemodrugs used in conditioning regimens

(1) busulfan (2) melphalan (3) thiotepa (4) carmustine (5) cyclophosphamide (6) cytarabine (7) etoposide (8) fludarabine (9)

7

List four (4) drug interactions and three (3) dose-limiting toxicites with Busulfan

DI through glutathione competition (a) acetaminophen (b) metronidazole (c) azole antifungals (d) phenytoin
TOX (1) mucositis (2) hepatotoxicity (3) seizures

8

How to manage busulfan hepatotoxicity?

1. veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
2. prophylax with ursodiol 300 mg PO q8hr
3. PK monitoring

9

How to manage busulfan seizure toxicity?

1. seizure prophylaxis with (a) phenytoin (b) benzodiazepines (c) levetiracetam

10

List drug interactions and dose-limiting toxicity with melphalan?

DI: none
TOX: mucositis, manage w/ 60-min cryotherapy

11

List drug interactions and two (2) dose-limiting toxicity with thiotepa?

DI: CYP2B6 inhibitor, give cyclophosphamide first.
TOX: mucositis, neurotoxicity (supportive care only)

12

List 1 drug interaction of carmustine and three (3) dose-limiting toxicity

DI: alcohol diluent so avoid dilsulfiram-drugs
TOX: hepatotoxicity, pulmonary toxicity (predisone 1 mg/kg/day), alcohol intoxication.

13

List three (3) drug interaction of cyclophosphamide and three (3) dose-limiting toxicity

DI: (a) CYP2B6 (b) 2C9 (c) 3A4
TOX: (1) hemorrhagic cystitis (2) cardiotoxicity (3) hepatotoxicity

14

List drug interactions with cytarabine and dose-limiting toxicity

DI: None
TOX: (1) neurotoxicity, uncommon at low dose.

15

List two (2) drug interactions with etoposide and two dose-limiting toxicities

DI: (1) CYP3A4 inducers (2) CYP3A4 inhibitors
TOX: (1) mucositis (2) hypotension during infusion

16

List drug interaction with fludarabine and dose-limiting toxicity

DI: none
TOX: neurotoxicity

17

List five (5) immunosuppressants used in bone marrow transplant

1. methotrexate
2. tacrolimus
3. cyclosporine
4. mycophenolate mofetil
5. sirolimus

18

List three (3) side effects of methotrexate

1. mucositis
2. myelosuppression
3. does NOT require alkalinization or leucovorin

19

List 1 DI and four TOX of tacrolimus

DI: CYP3A4 inhibitors or inducers (azole antifungals reduce dose by 50%)
tox: (1) hyperkalemia, hypomagnesemia (2) tremor (3) headache (4) renal dysfunction

20

List 1 DI and five TOX of cyclosporine

DI: CYP3A4 inhibitors or inducers
TOX: (1) hypertension (2) gingival hyperplasia (3) liver dysfunction (4) renal dysfunction (5) neurotoxicity

21

List 1 DI and 3 TOX of mycophenolate

DI: none
TOX: (1) myelosuppressive (2) nausea (3) diarrhea

22

List 1 DI and four TOX of sirolimus

DI: none
TOX: (1) GI upset (2) arthralgia (3) headache (4) renal dysfunction

23

List three (3) immunosuppressants with TDM and their goal trough levels

1. cyclosproine (150-350 nanogram/mL)
2. tacrolimus (5-15 ng/mL)
3. sirolimus (3-18 ng/mL)

24

List four prevention medications and their purpose

1. Cipro or Zosyn or cefepime (prevention of bacterial infection)
2. Voriconazole or Fluconazole (prevention of fungal infections)
3. Acyclovir or valacyclovir (prevention of HSV infections)
4. Bactrim DS (prevention of PCP infections)

25

List three (3) agents used in induction therapy

1. Antithymocyte globulin
2. Basiliximab
3. Alemtuzumab

26

List two (2) calcineurin inhibitors

1. cyclosporine
2. tacrolimus

27

List two (2) antiproliferatives

1. azathioprine
2. mycophenolate

28

List two (2) m-TOR inhibitors

1. sirolimus
2. everolimus

29

List two (2) other immunosuppressants used in solid organ transplant

1. corticosteroids
2. belatacept

30

List 3 aspects of thymoglobulin induction management

1. premedicate with acetaminophen/diphenhydramine for infusion-related reaction
2. monitor leukopenia and thrombocytopenia and dose adjust
3. CMV infection possible

31

List 3 aspects of basiliximab management

1. MOA: IL-2 receptor antagonist
2. monitor CBC
3. very well tolerated, pain at site of administration
4. no reported DDIs

32

List 4 aspects of alemtuzumab management

1. MOA: recombinant DNA-derived monoclonal antibody that binds to CD52
2. rapid and extensive lymphocyte depletion
3. premedication with acetaminophen/diphenhydramine for infusion
4. high incidence of adverse events

33

List 5 aspects of cyclosporine management

1. brand names not AB rated (non-modified requiers food, variable absorption; modified has consistent exposure)
2. MOA: binds to cyclophilin which inhibits calcineurin phosphatases, reducing t-cell activation
3. goal trough 50-400 ng/mL
4. metabolized by CYP3A4 and p-Gp inhibitor
5. monitor drug levels, CBC, electrolytes, BP, LFTs, pregnancy

34

List 5 aspects of tacrolimus management

1. Brand names (prograf 2 divided doses, advagraf 1 daily)
2. MOA: binds to FK-binding protein which inhibits calcineurin phosphatases
3. goal trough 5-15 ng/mL
4. avoid IV if possible because contains castor oil w/ anaphylaxis and nephrotox risk
5. CYP3A4 substrate
6. monitor drug levels, CBC, electrolytes, BP, LFTs, pregnancy

35

List most common dose-limiting tox for tacrolimus and cyclosporin

TAC: alopecia, diabetes, hand tremor, dysesthesias, headache, insomnia
CSA: HTN, hyperlipidemia, gingival hyperplasia, hirsutism

36

List five (5) aspects of azathioprine management

1. MOA: prodrug for 6-mercaptopurine which is antimetabolite
2. dose reduction in renal failure
3. monitor for signs of myelosuppression, CBC, BBW for lymphoma, pregnancy cat D.
4. leukopenia, thrombocyteopenia, hepatotoxicity
5. drug interactions: allopurinol & febuxostat; 6-mercaptopurine (avoid or dose decrease; ACE inhibitor (anemia and leukopenia); warfarin (increase warfarin dose)

37

List four (4) aspects of mycophenolic acid management

1. MOA: reversible inhibitor of inosine monophosphatate dehydrogenase, antiproliferative
2. monitoring: CBC, especially WBC (reduce if WBC<4), pregnancy cat D, no routine TDM.
3. side effects: (1) diarrhea (2) n/v (3) neutropenia (4) anemia (5) hypertension
4. interactions: (1) aluminum and Mg containing antacids (separate by 2 hr before and after); PPI (cellcept > myfortic); cholesytramine decreases absorption (separate by 2 hours before and after)

38

List four (4) aspects of sirolimus management

1. MOA: mTOR inhibitor, prevents progression from G1 to S phase)
2. can substitute for CNI or substitute for azathioprine/MPA derivative
3. metabolism: CYP3A4, PgP, half-life 62 hours
4. monitoring: hepatic function (dose adjust by decrease 1/3 in dysfunction), lipid panel, electrolytes, urinalysis, pregnancy cat C.
5. side effects: delayed wound healing (do not give within 30-90 days of surgery), leukopenia, thrombocytopenia, hyperlipidemia

39

List four (4) aspects of everolimus management

1. MOA: mTOR inhibitor
2. trough concentration 3-8 ng/mL
3. same ADR as sirolimus
4. monitor CBC, complete liver panel, lipid panel, blood glucose, pregnancy cat C.

40

List five (5) aspects of belatacept management

1. MOA: inhibit signal 2 by antagonizing CD80 and CD86 on antigen presenting cells
2. first long term IV maintenance immunosuppressive based on ABW
3. contraindicated in EBV seronegative patients (increased risk of lymphoproliferative disorder)
4. monitor prengancy cat C, serum creatinine, EBV status
5. potential option for stable transplant patients in steroid-sparing or CNI-sparing regimens
6. side effects fever, neutropenia, leukopenia, GI, cough, infection

41

List three categories of complications in post-solid organ transplant

1. malignancy (PTLD)
2. infection (BK virus, CMV, PCJ)
3. Chronic disease (osteoporosis, hypertension, hyperlipidemia, diabetes)

42

How to manage BK virus in PSOT?

1st line: decrease immunosuppression
2nd line: leflunomide vs cidofavir

43

How to manage CMV in PSOT?

1. Low risk: no prophylaxis.
2. Intermediate risk: valgancyclovir 450-900 mg x3 months.
3. high risk: valganciclovir 450-900 mg po QD x 6 months

44

How to manage PCJ in PSOT?

1. Prophylaxis x 6 months with Bactrim, Dapsone, pentamidine or Atovaquone

45

Three (3) aspects of hypertension management in PSOT

1. short-acting agents (clonidine, labetalol, hydralazine) to avoid hypotension
2. ACE/ARB - additive hyperkalemia with CNIs, increased SCr, decreasesd GFR
3. Nondihydropyridine CCBs - inhibit CYP450 resulting in elevated CNI levels

46

Two (2) aspects of hyperlipidemia in PSOT

1. Statin recommended for adult kidney tx patients
2. Statin-cyclosporine drug interactions (avoid simvastatin, lovastatin, atorvastatin, pitavastatin), USE 20 mg pravastatin, 20 mg fluvastatin, 5 mg rosuvastatin.