ILE 9 - Lymphoma (& oncologic emergencies)

what is lymphoma?

heterogenous group of lymphoproliferative disorders

- malignant transformation of immune cells in lymphatic system

what are the types of lymphoma?

hodgkin lymphoma

non-hodgkin lymphoma -- presence of B- or T-cell lymphocytes

although the cause of non-hodgkin lymphoma is unknown, what are some of the risk factors?

- congenital or acquired immunodeficiency (HIV/AIDs)

- autoimmune diseases

- Epstein Barr Virus infection

- diet: high intake meats & dietary fats

- occupational (herbicide exposure, lawn care pesticides, chemical solvents & dyes, radiation exposure)

which is more common in lymphoma: monoclonal proliferation of malignant B or T lymphocytes?

B-cells (85-90%)

how are lymphomas classified?

morphology/appearance

immunology (B or T lymphocytes)

disease entities

lymphoma is divided into 2 categories: B & T cell lymphomas. These categories are further divided into what sections?

- precursor cells

- mature cells

- grade

- aggressiveness

where do B-cell lymphomas typically present?

lymph nodes

spleen

bone marrow

where do T-cell lymphomas typically present?

extranodal sites (Skin, lungs)

what is the most common presentation of lymphoma? what are the symptoms?

peripheral lymphadenopathy

- localized or generalized

- rapid onset/progression (aggressive lymphomas)

- waxing/waning (indolent lymphomas)

- may lead to organ dysfunction

what are "B-symptoms" of lymphoma?

fever (temp >38°C)

wt loss (unexplained, >10% body weight w/in 6 mo)

night sweats

what are the most common sites of extra-nodal involvement w/ lymphoma?

GI & skin

symptoms of GI involvement w/ lymphoma?

N/V

obstruction

abdominal pain

palpable mass

GI bleeding

symptoms of bone marrow involvement w/ lymphoma?

anemia

thrombocytopenia

neutropenia

Excisional biopsy of entire lymph node is the preferred diagnostic tool for lymphoma. However, what can be done if no adenopathy?

biopsy cutaneous lesions, bone marrow, liver, extranodal organs (bone, lung, testes)

what history & physical exam should be conducted for lymphoma patients?

lymphadenopathy history

B symptoms

CBC

CMP

lumpar puncture in pts @ risk for CNS disease

describe Ann Arbor staging for lymphoma:

stage I: localized disease

II: ≥2 lymph node regions on same side of diaphragm

III: ≥2 node regions above & below diaphragm

IV: widespread disease

treatment of lymphoma is based on what criteria?

NHL disease entity

stage (doesn't correlate w/ cure)

performance status

what type of lymphoma is associated w/ long survival w/ or without treatment & is unlikely to be cured?

indolent lymphoma

what type of lymphoma is associated w/ short survival without treatment & poor performance status in which pt is unlikely to tolerate aggressive chemo

aggressive lymphomas

what treatment modalities for treating indolent lymphoma?

radiation alone

biologic therapy alone

multiagent chemo

what tx modalities for treating aggressive lymphoma?

multiagent chemotherapy

** single day, 21-day cycles

what tx modalities for treating very aggressive lymphoma (Burkitt lymphoma)?

aggressive, inpatient, multiagent chemo over multiple days

what is the CHOP or R-CHOP regimen for lymphoma tx?

Rituximab

Cyclophosphamide

H - doxorubicin (hydroxydaunomycin)

O - vincristine (Oncovin)

Prednisone

MOA of rituximab

mAb directed against CD20 antigen on B-lymphocytes

ADRs of rituximab

infusion rxns (fever, chills, HTN, flushing, Headache, body aches)

neutropenia

infection

administration requirements for rituximab?

slow titration (1st infusion given 50 mg/hr, can incr. by 50mg/hr to max 400 mg/hr)

premedicate w/ APAP, diphenhydramine

BBW of rituximab?

- infusion-related rxns

- mucocutaneous rxns

- hepatitis B reactivation

- progressive multifocal leukoencephalopathy

ADRs of cyclophosphamide

myelosuppression

GI toxicity

alopecia

infertility

carcinogenicity

hemorrhagic cystitis

nephrotoxicity

clinical pearls of cyclophosphamide?

nephrotoxic, so hydrate!!!

hemorrhagic cystitis ==> due to acrolein (dose dependent (>1 g/m^2)); counsel for adequate hydration & frequent voiding

MOA of doxorubicin?

DNA intercalation

-- topoisomerase II inhibition; iron chelation & oxygen free radical generation

ADRs of doxorubicin?

red discoloration of bodily fluids

cardiotoxicity

myelosuppression

mucositis

alopecia

clinical pearls of doxorubicin?

- obtain ECHO b4 tx & at regular intervals

- this drug is a vesicant

MOA of vincristine

binds tubulin & prevents polymerization

ADRs of vincristine?

constipation

neurotoxicity (peripheral neuropathy)

clinical pearls of vincristine?

fatal if given intrathecally

NOT myelosuppressive

vesicant!!

MOA of prednisone

inhibits cytokine produciton

alteration of oncogene expression

cell-cycle arrest & apoptosis

ADRs of prednisone

avascular necrosis

mood alteration

steroid myopathy

hyperglycemia

infections

HTN

edema

GI upset

etc.

administration requirements for prednisone?

give after food to reduce GI upset

is R-CHOP emetogenic?

YES!!! HIGHLY!! PREMEDICATE

does R-CHOP have a risk for febrile neutropenia?

YES- intermediate

** give pts prophylactic G-CSF if they have addnl risk factors or experience a delay in a cycle due to neutropenia

** consider prophylactic antimicrobials, antifungals, & antivirals

define hypercalcemia of malignancy:

albumin-corrected serum calcium >10.5 mg/dL (severe if 14 mg/dL or greater) in pt w/ cancer

** most common metabolic oncologic emergency

how does hypercalcemia of malignancy present?

- polyuria, polydipsia, dehydration

- anorexia, N/V, constipation

- fatigue, weakness, confusion, lethargy, coma

- bone pain

- acute kidney injury

- shortened QT & arrhythmias

risk factors for hypercalcemia of malignancy?

patient-specific: dehydration, renal insufficiency, immobility, older age

disease: squamous cell (lung, head, neck), breast, renal, multiple myeloma, etc.

tx: thiazides, lithium, calcium/vitamin D supplements, etc.

what causes bleeding (Disseminated intravascular coagulation (DIC))?

explosive tissue factor release + hyperfibrinolysis (factors consumed faster than they're made)

how does disseminated intravascular coagulation (DIC) present? what pt populations are @ highest risk?

petechiae, ecchymoses, oozing @ line sites, mucosal/GI bleeding, intracranial hemorrhage

acute promyelocytic leukemia, sepsis, hepatic dysfxn

what causes the oncologic emergency of thrombosis?

sustained low-grade tissue factor expression w/ preserved hepatic synthesis

virchow triad amplified by tumor

what is tumor lysis syndrome (TLS)?

oncologic emergency in which acute destruction of neoplastic cells occurs due to chemotherapy or overcrowding

--> release of intracellular contents into circulation, renal elimination overwhelmed, accumulation of metabolic products

how does tumor lysis syndrome present?

hyperuricemia

hyperkalemia

hyperphosphatemia

hypocalcemia

pre-existing conditions that can put pt @ risk for tumor lysis syndrome?

renal insufficiency

dehydration

hypotension

what tumor factors put a patient at risk for tumor lysis syndrome?

type of malignancy

bulky disease

high proliferative rate

highly responsive to therapy

does an elevated or decreased lactate dehydrogenase (LDH) put a patient at risk for tumor lysis syndrome?

elevated!!

what is the prophylaxis for tumor lysis syndrome?

** start 24-48 hrs b4 cytoreductive therapy

- aggressive hydration

- anti-hyperuricemic agents (allopurinol, rasburicase)

- loops (maintain urine output)

- correct existing metabolic abnormalities

- dietary restriction

what is the treatment for tumor lysis syndrome?

goal: preserve renal fxn

- aggressive hydration

- anti-hyperuricemic agents (allopurinol, rasburicase)

- aggressive monitoring (q6h labs, PRN cardiac)

- eliminate potential iatrogenic causes

- dialysis/continuous renal-replacement therapy

why does hyperuricemia occur?

due to release & catabolism of nucleic acids

MOA for allopurinol for TLS?

administration instructions?

it inhibits xanthine oxidase

PO TID after meals

** if PO unavailable, transition to rasburicase

** start 24 hrs b4 chemotherapy

MOA of rasburicase for TLS?

administration instructions?

recombinant urate-oxidase; converts uric acid to allantoin

labeled dosing: mg/kg dosing once daily x 5 days

off-label: 3-7.5 mg fixed dose on demand

what is the contraindication for rasburicase in the tx of TLS?

CI in known glucose-6-phosphate dehydrogenase (G6PD) deficiency

clinical s/s of hyperkalemia?

muscle cramps

paresthesias

dysrhythmias

ventricular fibrillation

cardiac arrest

management strategies for hyperkalemia?

hyper-hydration

dietary restriction

sodium polystyrene sulfonate

diuretics, albuterol

insulin (+ dextrose)

sodium bicarb

dialysis

clinical s/s of hyperphosphatemia?

N/V

diarrhea

lethargy

seizures

acute kidney injury

management strategies for hyperphosphatemia?

hyper-hydration

dietary restriction

phosphate binders

dialysis

clinical s/s of hypocalcemia?

muscle cramps

tetany

hypotension

dysrhythmia

management strategies for hypocalcemia?

avoid treatment in asymptomatic patients