6303: Lymphoma, TLS, + Prostate CA

-T cells

-B cells

Types of lymphocytes; both produced in Bone marrow ( → matures in spleen)

Malignancy of the cells in the lymphatic system

Lymphoma

-Indolent Lymphoma (follicular lymphoma)

-Aggressive Lymphoma (diffused large B-cell lymphoma, DLBCL)

-Highly Aggressive Lymphoma (Burkitt Lymphoma)

Non-Hodgkin Lymphoma Types

-High fevers

-Drenching night sweats

-Unexpected weight loss (10% in 6 months)

Constitutional Sx (B symptoms) of Lymphoma

-Enlarged lymph nodes (Painless Lymphadenopathy)**

-Hepatosplenomegaly (enlarged spleen/liver)

-Fatigue/Asthenia

Signs and Sx of Lymphoma: Other

Lymph node biopsy

Gold standard for Lymphoma Diagnosis

One lymph node or localized site

Stage 1 Lymphoma

2 or more lymph nodes on the SAME SIDE of Diaphragm

Stage 2 Lymphoma

Lymph node involvement ABOVE and BELOW the Diaphragm

Stage 3 Lymphoma

Diffused/Disseminated involvement in an EXTRANODAL Organ

Stage 4 Lymphoma

-Slow growing (can have cells not actively growing/dividing)

-Chronic relapsing disease

-CD20+

Characteristics of Indolent Lymphoma

-Fast growing

-CD20+

Characteristics of Diffuse Large B-cell Lymphoma

-All cells are actively growing at ALL times

-Requires immediate Tx ⚠️

-CD20+

Characteristics of Burkitt Lymphoma

-Sx: chronic pruritus, diffused skin rash

-Reed-sternberg cells

-CD30+, CD15+

Characteristics of Classical Hodgkin Lymphoma

Stages 1-4: CURE

Goal for:

-Diffuse Large B-cell Lymphoma

-Burkitt Lymphoma

-Classical Hodgkin Lymphoma

-Stage 1-2: CURE

-Stages 3-4: CONTROL**

Goal for:

-Indolent Lymphoma

-Radiation only

Tx for Stage 1-2 of Indolent Lymphoma

-Observation only EXCEPT if there's symptoms...

-If Sx: Rituximab + Chemotherapy

Tx for Stage 3-4 of Indolent Lymphoma

-Rituximab

-Cyclophosphamide

-Doxorubicin

-VinCristine

-Prednisone

"R-CHOP"

Tx regimen for Diffuse Large B-cell Lymphoma

"HyperCVAD A"

-Rituximab

-Cyclophosphamide

-Doxorubicin

-VinCristine

-Dexamethasone

+

"HyperCVAD B"

-Rituximab

-Cytarabine

-MTX

Tx Regimen for Burkitt Lymphoma

"ABVD" + Radiation

-Doxorubicin

-Bleomycin

-VinBlastine

-Dacarbazine

Tx Regimen for Hodgkin Lymphoma Stages 1-2

"AVD" + Nivolumab [NO RADIATION HERE BTW]

-Doxorubicin

-VinBlastine

-Dacarbazine

Tx Regimen for Hodgkin Lymphoma Stages 3-4

-Severe N/V

-Hepatotoxicity

ADRs of Dacarbazine

-Immune related rxns (-itis'es)

ADRs of Nivolumab (an ICI)

-CODOX-M alternating w/ IVAC

-Dose-adjusted EPOCH

Other Tx regimens for Burkitt Lymphoma (not main one?)

This lymphoma has high rates of CNS penetration and requires IT (intrathecal) Chemotherapy

Burkitt

On TOP of B symptoms and Painless Lymphadenopathy:

has + Chronic Pruritus/Diffused Skin Rash

Sx of Hodgkin Lymphoma

This is different from chemotherapy in that it binds to ALL cells that express its biomarker target; it is NOT affected by speed of cell growth (therefore we can use it in Follicular/Indolent Lymphoma)

Rituximab

[BBW ☠️ ]

-Infusion rxns → premedicate w/ Diphenhydramine and Tylenol

-Tumor Lysis Syndrome

-PML

[Other]:

-Hepatitis B Reactivation → HepB test (and ppx if Anti-HBc+ or HBsAg+)

ADRs of Rituximab

-Irritability

-Insomnia

-GI upset

-Leukocytosis

-Hyperglycemia

Short-term ADRs of Steroids

-INC'd infections

-Bone Mineral Density Loss

-Peptic Ulcers

-Weight gain

-Adrenal Insufficiency

Long-term ADRs of Steroids

-A life threatening emergency that occurs from a massive release of cellular components into the blood after rapid lysis of malignant cells

-Often presents 12-72H after tx, occcurs spontaneously after cytotoxic chemo

Tumor Lysis Syndrome definition

-Hyperkalemia

-Hyperphosphatemia

-Hyperuricemia

-HYPOcalcemia

Metabolic Disturbances of TLS

-Fatigue

-Muscle weakness

-Dehydration

-Seizure

-Renal impairment

-Cardiac arrhythmias

Sx of TLS

-Uric acid crystallization

-Calcium-Phosphate Precipitation

→ AKI

This leads to seizures, tetany, muscle cramps

HYPOcalcemia

This leads to cardiac dysarrthmias

INC in potassium

8.5 to 10.5

Normal Calcium Serum range

2.5 to 4.5

Normal Phosphorus levels

3.5 to 5

Normal Potassium levels

4 to 8.6

Normal Uric acid levels

What do we use to treat HYPO/Low Calcium?

Sevelamer (treat Hyperphos → free up the calcium from Ca-Phos precipitation)

-Bulky disease (>10 cm) **also elevated LDH and WBC

-High tumor proliferation rate

-Chemo-sensitive (rapid response to therapy)

Characteristics of TLS

-Maintenance fluids

-+/- Allopurinol

TLS Prophylaxis for LOW Risk [in Peds or Adults]

-Hyper-hydration

-Rasburicase

TLS Prophylaxis for HIGH Risk [in Peds or Adults]

**also for Intermed. Risk in Peds

-Hyper-hydration

-Allopurinol

TLS Prophylaxis for Intermediate Risk [in Adults]

-N/V/D

-Muscle cramps, spasms

-Lethargy, confusion

-Seizure

-Ca-Phos precipitation → AKI

Sx of Hyperphosphatemia

-Hydration

-Dietary phosphate restriction

+/- Phosphate binders (to prevent absorption)

Tx of Hyperphosphatemia

-AVOID IV/PO K+ supplementation

-Temporarily shift K+ intracellularly (Regular insulin IVP + D50%W IVP / Albuterol / Sodium bicarb if acidotic)

-Remove K+ (Loop diuretics)

-Long-term management (Lokelma: sodium zirconium cyclosilicate)

Hyperkalemia Tx if K+ 6.1 to 6.5 WITHOUT EKG changes

-AVOID IV/PO K+ supplementation

-**STABILIZE CARDIAC MEMBRANE (with Calcium gluconate or chloride)

-Temporarily shift K+ intracellularly (Regular insulin IVP + D50%W IVP / Albuterol / Sodium bicarb if acidotic)

-Remove K+ (Loop diuretics)

-Long-term management (K+ binder Lokelma: sodium zirconium cyclosilicate)

Hyperkalemia Tx if K+ > 6.5 OR we have EKG changes (peaked t-waves, widened PR interval, widened QRS complex, absent p-waves)

-Sevelamer Carbonate (Renvela)

-Calcium Acetate (Phoslo)

-Lanthanum Carbonate (Fosrenol)

Phosphate Binders

Calcium Gluconate 1000 mg IV slow infusion (NTE 200mg/min)

Used for SYMPTOMATIC Hypo-Calcemia (caution w/ treating asymptomatic)

-IV hydration

-Initiation of continuation of Hypouricemic Agent

-Supportive care

-Correction and close monitoring of Electrolytes

Treatment of TLS

-Cardiac dysfunction

-Urinary obstruction

-Renal failure

Fluid Restrictions

Inhibits xanthine oxidase → DEC FORMATION of uric acid

Allopurinol MoA

HLA-B*5801 +

Contraindication for Allopurinol use

For TLS Prophyalxis (of hyperuricemia) in ppts w/ Intermed-High risk of TLS who cannot tolerate Allopurinol or when Rasburicase is contraindicated

Febuxostat Indication

-BBW: HF

-Concurrent use w/ Azathioprine or Mercaptopurine

Contraindications for Febuxostat use

Recombinant urate-oxidase enzyme → breaks down existing uric acid for excretion (GETS RID OF existing uric acid)

MoA of Rasburicase

BBW: G6PD Deficiency

Contraindications for Rasburicase use

-Mainstay of Ppx and Tx of TLS (enhances urine flow, excretion of uric acid/phosphate/potassium)

-2 to 3 L/m2/day

-Goal: Maintain UOP of 80-100 ml/m2/hr

Hydration, IV fluids

-GnRH agonist (Leuprolide, Goserelin)

-GnRH antagonist (Degarelix)

-Androgen receptor inhibitor (Enzalitamide (Xtandi))

-Androgen biosynthesis inhibitor (Abiraterone (Zytiga))

Drugs for Metastatic Prostate Cancer (ADTs)

-GnRH Agonist (Leuprolide, Goserelin)

Drugs for Non-Metastatic Prostate Cancer Adjuvant tx AFTER XRT

-Menopausal sx

-Bone loss

-Tumor flare

ADRs of GnRH Agonists

-Menopausal sx

-Bone loss

[NO TUMOR FLARE]

ADRs of GnRH Antagonists

-Menopausal sx

-Bone loss

-Hepatotoxicity

ADRs of Androgen Receptor inhibitors (i.e. Enzalutamide)

-Menopausal sx

-Mineralcorticoid Excess sx: HTN, fluid retention, HYPOkalemia (→ give w/ Prednisone)

-Also teratogenic

ADRs of Androgen Biosynthesis inhibitors (i.e. Abiraterone)

-Radical Prostatectomy 🔪 (better for younger ppts w/ high-risk disease)

-Radiation Therapy +/- "ADT" x2-3 years (better for intermediate risk disease, poor surgical candidates)

-Active Surveillance (better for older ppts w/ lower-risk disease)

Prostate Cancer Initial Tx Options for NON-Metastatic

-"ADT" (GnRH Agonist or Antagonist)

PLUS (+)

-Enzalutamide (androgen receptor inhib) OR

-Abiraterone (androgen biosynthesis inhib) + Prednisone

Prostate Cancer Tx for METASTATIC → Castration Sensitive (M1 CSPC)

-Continue "ADT"

PLUS (+)

-Docetaxel

Prostate Cancer Tx for METASTATIC → Castration Resistant (M1 CRPC)

-Age over 65

-Family Hx (1st degree relatives, esp if

Risk Factors for Prostate Cancer

Transrectal Biopsy

Diagnosis for Prostate Cancer

Why is PSA screening a shared decision making and not recommended?

It does not result in DEC'd mortality

This is a 1st generation Androgen Receptor Inhibitor that is NOT used for Tx of Prostate cancer but rather to PREVENT Tumor Flares (use for short-term management of sx)

Bicalutamide (Casodex)