HSCT

Graft =

hematopoietic stem cells

Graft sources → 3

1. bone marrow

2. *peripheral blood stem cell (most common)

3. umbilical cord blood

IMMUNOLOGY OF GRAFT SOURCES

1. __________ → own stem cells are used

2. __________ → identical twin’s stem cells are used

3. __________ → donor stem cells used, matched based on HLA antigens

1. autologous

2. syngeneic

3. allogeneic

Goals of conditioning regimen

1. Autologous HSCT

2. Allogeneic HSCT

1. eradicate disease

2. eradicate disease + immunosupp

AUTO HSCT

1. Supp care →

2. Complications → Relatively well tolerated (4)

3. Long term complication →

1. GFs + transfusion supp, antimicrobial prophylaxis

2. NV, infxn, fatigue, diarrhea

3. secondary malignancies

ALLO HSCT

1. Supp care →

2. Complications →

1. same as auto + immunosupp

2. same as auto + more infxn, graft vs host disease, hepatic SOS (sinusoidal obstructive syndrome)

ACUTE LEUKEMIAS

1. type 1 →

2. type 2 →

3. Major goals of therapy (for both) → (*CR complete remission)

1. ALL more common in children, CNS prophylaxis routine

2. AML more common in adults, CNS prophylaxis NOT routine

3. achieve rapid CR → maintain CR → minimize tox

ALL LYMPHOCYTIC Treatment Phases

1. consolidation (chemo and/or allo HSCT)

2. interim maint

3. delayed intensification

4. interim maint II

5. CNS prophylaxis w intrathecal chemo

Adult AML Treatment Phases

consolidation (chemo and/or allogeneic HSCT)

ACUTE LEUKEMIA PEARLS

1. Intrathecal chemo →

2. High dose cytarabine (_______ mg/m²) → __________ to prevent corneal toxicity & hemorrhagic conjunctivitis

1. DO NOT USE preservative-containing solutions/drugs

2. >1000 → use steroid eye drops

CHRONIC MYELOID LEUKEMIA (CML)

Mainstay of therapy →

BCR-ABL tyrosine kinase inhib

CHRONIC MYELOID LEUKEMIA (CML)

Generic → *Toxicity

1. ALL CAN CAUSE ___________

2. Gleevec →

3. Sprycel →

4. Tasigna →

5. Iclusig →

1. myelosupp

2. imatinib → fluid retention/edema

3. dasatinib → pleural/pericardial effusions

4. nilotinib → +QTc BW

5. ponatinib → arterial thrombosis, hepatotox, VTE, HF

CHRONIC LYMPHOCYTIC LEUKEMIA

1. Clinical presentation:

2. *1st line tx if NO deletion 17p →

3. →

4. →

1. leukocytosis

2. acalabrutinib (Calquence) ± obinutuzumab (Gazyva)

3. venetoclax (Venclexta) + obinutuzumab (Gazyva)

4. zanubrutinib (Brukinsa)

CML/CLL DRUG PEARLS

1. CML → _______ generic & less expensive. but generally ____ preferred than other BCR/ABL inhibitors
   Patients take BCR/ABL inhibitors long term, pharmacists are key in monitoring for toxicities, DDIs, compliance

2. CLL → may see _____________ after initiation of venetoclax, ibrutinib, and acalabrutinib

3. CLL → ___________, dose is ramped up initially to mitigate risk to TLS (tumor lysis syndrome)

1. imatinib, less

2. transient lymphocytosis

3. venetoclax

1. HODGKIN LYMPHOMA

2. NON-HODGKIN LYMPHOMA

1. classical HL, 4 subtypes, nodular lymphocyte-predominant HL

2. B cell & T cell lymphomas

CLASSICAL HODGKIN LYMPHOMA (HL)

_______ is the prototype chemotherapy regimen, NOT USED FOR NHL

ABVD

NON-HODGKIN LYMPHOMA CLINICAL PRESENTATION

1. ~40% present with B symptoms → 3

2. Fatigue, malaise, pruritus, peripheral _________

1. unexplained weight loss >10% of BW, unexplained fever, night sweats

2. lymphadenopathy

NON-HODGKINS 1ST LINE TX DEPENDS ON LYMPHOMA SUBTYPE

1. DLBCL →

2. Follicular lymphoma →

3. Burkitt lymphoma →

4. H pylori associated lymphoma →

1. RCHOP or polatuzumab + RCHP ± radiation

2. watch-and-wait, bendamustine + rituximab, RCHOP

3. hyperCVAD, dose-adj EPOCH

4. if early, tx by eradicating H pylori

R-CHOP REGIMEN

1. →

2. →

3. →

4. →

5. →

6. Cycle every _____

1. Rituximab

2. Cyclophosphamide

3. Doxorubicin

4. Vincristine

5. Prednisone

6. 21d

RITUXIMAB

1. _________ chimeric IgG1 mAb

2. Most common side effects → ________, fever, lymphopenia, chills, infxn, asthenia

3. ^ required premedication:

4. Formulations

5. WARNINGS & PRECAUTIONS → 4

1. antiCD20

2. infusion rxns

3. antihistamine + APAP ± steroid

4. IV, SQ

5. infusion rxns (1st dose!), HBV rxns, sev mucocutaneous rxns, PML (progressive multifocal leukoencephalopathy)

RITUXIMAB & HBV REACTIVATION

1. Screen all patients receiving rituximab or other anti-CD20 mAb → core antibody + surface antigen

2. IF EITHER TEST IS POSITIVE, prophylaxis → ______ preferred

3. Monitor ________ and ______ during tx

4. Continue prophylaxis for at least _____ after completion of therapy

1. anti-HBc IgG + HbsAG

2. entecavir

3. HBV DNA, LFTs

4. 12m

ANTHRACYCLINE CARDIOTOXICITY

1. Acute

2. Subacute

3. Chronic/delayed

1. w/in 1w

2. w/in weeks

3. ~1yr post tx, IRREVERSIBLE

Multiple proposed mechanisms of anthracycline cardiotoxicity (CHRONIC/DELAYED)

1. cardiomyocytes _______

2. _____ formation

3. **_________ accumulation

4. dysregulation of cardiomyocytes ________

1. apoptosis

2. ROS

3. mitochondrial iron

4. autophagy

ANTHRACYCLINE CARDIOTOXICITY risk is related to the _________ dose

cumulative

1. What is her total cumulative dose of doxorubicin after 3 cycles?

2. What is her risk for LVEF decline and HF at this time?

1. 150 (look at the mg/m²)

2. 7%, 0.2%

ANTHRACYCLINE monitoring recommendation →

baseline LVEF by echocardiogram or MUGA

ANTHRACYCLINE CARDIOPROTECTION

1. Limit lifetime ________

2. _____________

3. Cardioprotectant → ONLY FOR DOXORUBICIN

4. Use ________ formulation if appropriate (Doxil)

1. cumulative dose

2. prolong inf rate

3. dexrazoxane (Zinecard)

4. liposomal

DEXRAZOCANE (ZINECARD)

1. MOA

2. Use after _____ mg/m² of doxorubicin has been given

3. Dose ratio dexrazoxane:doxorubicin

4. Infuse immediately _______ doxorubicin infusion

1. iron chelator, topo II inhib

2. 300

3. 10:1

4. BEFORE

LATE EFFECTS OF CHEMOTHERAPY (Survivorship)

1. Effects on __________

2. _____________

3. Other: ________, avascular necrosis, pulmonary fibrosis, hearing loss, endocrine dysfx, cataracts

1. fertility

2. secondary malignancies

3. cardiotox

SUMMARY:

1. chronic myeloid leukemia

2. chronic lymphocytic leukemia

3. hodgkin lymphoma

4. non-hodgkin lymphoma (DLBCL)

1. BCR-ABL tyrosine kinases inhib (-tinibs)

2. acalabrutinib ± obinutuzumab, venetoclax + obinutuzumab, zanubrutinib

3. ABVD

4. RCHOP, polatuzumab + RCHP ± radiation

HSCT REGIMEN → 5

1. mobilization

2. collection

3. conditioning

4. transplant

5. engraftment