Exam 4

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

List three (3) components of conditioning regimens

Answer 5

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

Question 6

List six (6) chemodrugs used in conditioning regimens

Answer 6

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

Question 7

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

Answer 7

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

Question 8

How to manage busulfan hepatotoxicity?

Answer 8

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

Question 9

How to manage busulfan seizure toxicity?

Answer 9

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

Question 10

List drug interactions and dose-limiting toxicity with melphalan?

Answer 10

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

Question 11

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

Answer 11

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

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

List drug interactions with cytarabine and dose-limiting toxicity

Answer 14

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

Question 15

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

Answer 15

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

Question 16

List drug interaction with fludarabine and dose-limiting toxicity

Answer 16

DI: none
TOX: neurotoxicity

Question 17

List five (5) immunosuppressants used in bone marrow transplant

Answer 17

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

Question 18

List three (3) side effects of methotrexate

Answer 18

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

Question 19

List 1 DI and four TOX of tacrolimus

Answer 19

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

Question 20

List 1 DI and five TOX of cyclosporine

Answer 20

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

Question 21

List 1 DI and 3 TOX of mycophenolate

Answer 21

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

Question 22

List 1 DI and four TOX of sirolimus

Answer 22

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

Question 23

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

Answer 23

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

Question 24

List four prevention medications and their purpose

Answer 24

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)

Question 25

List three (3) agents used in induction therapy

Answer 25

1. Antithymocyte globulin 2. Basiliximab 3. Alemtuzumab

Question 26

List two (2) calcineurin inhibitors

Answer 26

1. cyclosporine | 2. tacrolimus

Question 27

List two (2) antiproliferatives

Answer 27

1. azathioprine | 2. mycophenolate

Question 28

List two (2) m-TOR inhibitors

Answer 28

1. sirolimus | 2. everolimus

Question 29

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

Answer 29

1. corticosteroids | 2. belatacept

Question 30

List 3 aspects of thymoglobulin induction management

Answer 30

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

Question 31

List 3 aspects of basiliximab management

Answer 31

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

Question 32

List 4 aspects of alemtuzumab management

Answer 32

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

Question 33

List 5 aspects of cyclosporine management

Answer 33

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

Question 34

List 5 aspects of tacrolimus management

Answer 34

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

Question 35

List most common dose-limiting tox for tacrolimus and cyclosporin

Answer 35

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

Question 36

List five (5) aspects of azathioprine management

Answer 36

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)

Question 37

List four (4) aspects of mycophenolic acid management

Answer 37

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)

Question 38

List four (4) aspects of sirolimus management

Answer 38

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

Question 39

List four (4) aspects of everolimus management

Answer 39

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.

Question 40

List five (5) aspects of belatacept management

Answer 40

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

Question 41

List three categories of complications in post-solid organ transplant

Answer 41

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

Question 42

How to manage BK virus in PSOT?

Answer 42

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

Question 43

How to manage CMV in PSOT?

Answer 43

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

Question 44

How to manage PCJ in PSOT?

Answer 44

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

Question 45

Three (3) aspects of hypertension management in PSOT

Answer 45

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

Question 46

Two (2) aspects of hyperlipidemia in PSOT

Answer 46

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.