Oncology 8/25 Spinler

cytopenias to diagnose aplastic anemia

need at least two

neutropenia: ANC < 500

thrombocytopenia: PLT < 20,000

absolute reticulocyte count: <60,000

ANC formula & ranges

ANC = (10 * WBC) * (%PMN + %bands)

normal: >1500

mild: 1000-1500

moderate:500-999

severe: <500

severe aplastic anemia treatment options

ideal therapy is stem cell transplant with matched donor

in absence of donor —> TPO-RA (thrombopoietin receptor agonist) + IST (intensive immunosuppresive therapy) = triple therapy

• eltrombopag

• ATG(AM)

• cyclosporine

what is a complete response to IST?

1. Hb normal for age and gender (>10-11)

2. neutrophils > 1.5

3. PLT > 150

give overview of triple therapy IST for AA

1. eltrombopag 150mg given orally starting day 1 through 6 months

2. ATGAM/hATG given daily for 4 consecutive days

   1. - give with prednisone for 21 days to prevent serum sickness

3. cyclosporine A given daily in 2 divided doses for 2 years

who requires lower dose of eltrombopag? what dose?

75mg to

East/SE asian ancestry OR

class A,B,C hepatic impairment

eltrombopag: primary AE, ocular AE, testing consideration, unique AE , pregnancy & lactation considerations

hepatotoxicity is common, boxed warning

may cause cataracts

may interfere with lab tests (colored)

may cause cytogenic evolution, may lead to malignancy

do not breast feed

use contraception, avoid pregnancy

eltrombopag monitoring and adjustments

PLT

—

adjust to keep above >50

begin to reduce when 200-400

hold dose when >400

ALT/AST

—

do not start if ≥5x ULN, adjust to maintain ≤6x ULN

eltrombopag DDIs (name the 3)

1. inhibits OATP, increase statin exposure, reduce rosuvastatin 50%

2. chelates Fe, Ca, Al, Mg, Zn

3. inhibits UGT, avoid with deferiprone

administration considerations of eltrombopag

take on an empty stomach OR with a low calcium meal

2hrs before or 4hrs after other meds, especially divalent cations

ATGAM: severe AE, administration consideration, less severe AE

may cause anaphylaxis!

-

must be given through central vein

-

may cause serum sickness, abated with 21 days of prednisone

acute splenic sequestration: signs, treatment

signs: low Hb/HCT, hypotension and shock

treat with broad spectrum antibiotic (ex ceftriaxone) to manage bacterial infections while spleen is less functional

biggest stroke prevention intervention for SCD

chronic transfusion therapy when transcranial doppler shows >200 cm/s (rate of flow)

pharmacotherapy to manage/prevent associated SCD complications: CKD, cataracts, priapism, hemolysis

CKD: ACEi

cataracts: VEGF inhibitor, ex. ranibizumab

priapism: prevent with hydroxyurea (common theme for SCD complications)

hemolysis: supplement folic acid

HbS goal for SCD patients on chronic transfusion therapy: manage iron overload, prevents what complication

HbS < 30% (0.)30

manage Fe overload with deferasirox and deferipone

prevents stroke

pneumococcal prophylaxis for SCD patients

children <3

• oral Pen VK or amoxicillin

children 3-5

• oral Pen VK

may use erythromycin if allergic

remember the pneumococcal conjugate vaccine

which vaccines for all SCD

pneumococcal, influenza (NOT FLUMIST, live), meningococcal

hydroxyurea: goal, monitoring parameters, adjustments

goal: HbF of 15-20%

monitor blood count, HbF, SCr, ALT

remember to pregnancy test!! very teratogenic

dose adjust for CrCl<60

two SCD gene therapies: cells that may fail to engraft, reason for hypersensitivity, hematologic risk —> which has BBW?

Casgevy (exagamglogene) and Lyfgenia (lovotibeglogene)

platelets and neutrophils may fail to engraft

hypersensitivity due to DMSO and dextran 40 in formulations

rare risk of hematologic malignancy due to off target gene editing, boxed warning on Lyfgenia

iron chelation goals, when to start

goal of normalized iron level: transferrin sat < 50% and serum ferritin < 500

goal Hb of 9-9.5

start chelation when PT receives 10 transfusions

DFX: name, adjustment, contraindications, ROA, boxed warnings

deferasirox

adjust for renal impairment

contraindicated for eGFR < 40

ROA: oral

BBWs: renal failure, fatal GI hemorrhage, hepatic injury and failure

DFO and DFP: names, ROAs, myelosuppresive?, boxed warnings, administration considerations

DFO: deferoxamine, DFP: deferiprone

DFO = IV or SubQ, DFP = oral

DFP is myelosuppresive, DFO not

DFP has BBW for agranulocytosis

must separate DFP 4 hours from divalent cations

iron chelator and gene therapy considerations

betibeglogene (Zynteglo): avoid iron chelators within 7 days of prior conditioning therapy, avoid myelosuppresive (DFP) within 6 months of gene

exagamglogene (Casgevy): avoid iron chelators

lovotibeglogene (Lyfgenia): avoid iron chelators

which iron chelators need renal adjustment

deferasirox (DFX) and deferoxamine (DFO)

luspatercept: purpose, warnings (4)

RBC maturation agent (TGF beta inhibitor) for beta thalassemic anemia

1. extra-medullary hematopoietic masses, may cause spinal cord compression

2. embryo-fetal tox

3. hypertension

4. thrombosis

factor VIII dosing: dose of (blank) increase plasma levels by (blank)

factor IX dosing: dose of (blank) increase plasma levels by (blank)

1 unit/kg —> 2%

1 unit/kg —> 1%

MOAs and treatable diseases: emicizumab, fitusiran, marstacimab, concizumab, mim8

avoid DDAVP with drugs that can cause (blank) like (2,3)

1. hyponatremia

2. loop diuretics

3. corticosteroids

(1) can be used before dental procedures, (2) can be used before dental procedures and heavy menstruation

1. aminocaproic acid

2. tranexamic acid