Onc lec 2

What does ALL stand for?

acute lymphocytic leukemia

What does AML stand for?

acute myelogenous leukemia

What does CLL stand for?

chronić lymphocytic leukemia

What does CML stand for?

chronic myelogenous leukemia

What is lymphadenopathy?

abnormal enlargement of the lymph nodes, typically >1cm

What are bacterial ecologies for LAD?

TB, cat scratch fever

What are viral etiologies for viral LAD?

HIV, infectious mononucleosis

What are protozoan etiologies for LAD?

toxoplasmosis

What labs do you order for LAD?

CBC w/ diff

VDRL or RPR (r/o syphillis)

HIV

LFTs

Hepatitis panel

EBV (r/o mononucleosis)

ANA (r/o rheumatic disease)

TSH

CT neck/chest/abdomen/pelvis- ID adenopathy

what are patients s/p splenectomy at an increased risk of?

sepsis caused by encapsulated bacteria such as s. pneumoniae, h. influenzae, and n. meningitides

What need to be given before a splenectomy?

pneumococcal (pneumovax 23, Prevnar - 13), Hib, and meningococcal vaccinations

What do children s/p splenectomy require until adulthood?

prophylactic antibiotics: PCN VK

What is leukemia?

progressive, malignant disease of bone marrow (blood forming organ) marked by distorted proliferation and development of leukocytes and/or their precursors in the bone marrow and peripheral blood

What are the abnormal cells that multiply in leukemia called?

blasts

What are etiologies of leukemia?

unknown, ionizing radiation, toxins (benzene) chemotherapeutic agents (alkylating), viruses (EBV, HTLV-1)

incidence increases w/ age and FHx

How are leukemias classified?

cell type- myeloid or lymphoid

time of onset- acute or chronic

What is the hallmark of leukemia?

pancytopenia or leukocytosis w/ circulating blasts

(abnormal counts w/ circulating blasts)

What abnormal labs would require an emergent hematology/oncology consult?

presence of blasts in a peripheral blood differential or smear

What is required for definitive diagnosis of leukemia?

bone marrow aspiration and biopsy

What is M/E ratio?

myeloid / erythroid ratio- compares number of myeloid cells (WBC precursors) to erythroid cells (RBC precursors)

What does a bone marrow aspiration and biopsy show you?

M/E ratio, cell differential, presence of abnormal cells, cellularity, bone marrow structure

What is flow cytometry?

cells are suspended in a fluid and flow one at a time through a specialized light → cells are tagged w/ markers (CD) for identification

can be performed on peripheral blood or BM aspirate to identify/categorize blasts/abnormal cells (its quick but you have to know what you’re looking for)

What is the most common acute leukemia in adults?

AML (more common >60 y/o)

How is AML classified?

risk stratification based on specific mutations - high, intermediate, low risk

(no stages for leukemia)

What is de novo AML?

no pre-existing hematologic condition

what is therapy related AML?

develops bc of previous chemotherapy or radiation

worse prognosis

What is secondary AML?

arises form previous hematologic condition (MDS, PNH, MF, ET)

clinical presentation of AML (will prob be on a vignette Q)

fatigue, SOB, inc infection, inc brusing/bleeding (epistaxis, gingival bleeding, menorrhagia), fever (tumor fever vs infection), night sweats, bone and joint pain

physical exam findings for AML

allow, petechiae/purpura, stomatitis, gingival hyperplasia, myeloid sarcoma, leukemia cutis, ± LAD, ± hepatosplenomegaly

what would you find on a peripheral smear in AML?

auer rods- rod shaped structures in cytoplasm

What would you see on a CBC in an AML patient?

anemia, neutropenia, thrombocytopenia, blasts on differential

In a bone marrow biopsy, what percentage of myeloblasts in considered AML?

over 20%

What is the prognosis of AML based on?

the chromosomal abnormalities that are driving the leukemia

What is the tx for AML that is considered good risk?

chemotherapy alone

What is the tx for AML that is considered poor risk?

chemotherapy followed by allogenic stem cell transplant

what is induction chemotherapy?

initial tx for AML that should be initiated immediately after dx. goes is to de-bunk disease and induce remission

What drugs are used to induction chemotherapy for AML?

anthracycline (daunorubicin) + cytarabine (Ara-C)

requires 1 month hospital stay

consolidation chemotherapy AML

given after remission is achieved, goal is to consolidate any microscopic remaining disease

HiDAC- high-dose cytarabine x 4 cycles

allogeneic stem cell transplant

tx given to intermediate / high risk AML that replaces damaged/diseased bone marrow with healthy donor’s

(risk of prolonged immunosuprresion & GVHD)

What are complications seen w/ AML?

anorexia, weight loss, N/V, infection, tumor lysis syndrome, DIC (more common in APL)

what is seen w/ tumor lysis syndrome?

hyperuricemia, hyperkalemia, hyperphosphatemia, elevated Cr, or hypocalcemia

What medical emergency is seen w/ AML?

APL- acute promyelocytic leukemia

maturation process stopped at promyelocytes, high rate of mortality due to hemorrhage (DIC)

What is considered high risk APL?

WBC >10,000

What is considered low risk APL?

WBC <10,000

How do you tx APL?

ATRA- all-trans retinoid acid (vitamin a)

start therapy ASAP

What do you need to watch out for when treating APL w/ ATRA?

differentiation syndrome and hyperleukocytosis

epidemiology of CML?

results form overproduction of myeloid cells

insidious onset, but can become acute if not identified

onset typically >65 y/o

What is the 5 year survival rate of CML?

90%

Etiology of CML

specific genetic abnormality- Philadelphia chromosome (Ph)- balance gene translocation b/ long arms of chromosome 9 and 22 [t(9;22)]

results in creation of BCR-ABL oncogene which results in uncontrolled proliferation

What is the clinical presentation of CML?

often asx- incidentally discovered on routine CBCs

fevers, fatigue, splenomegaly

What are the 3 phases of CML?

chronic phase, accelerated phase, blast crisis

what is the chronic phase of CML?

indolent disease, raised WBC w/ left shift

what is the accelerated phase of CML?

worsening WBC count, unresponsive to therapy, 10-19% blasts in BM, >20% basophils in blood, additional chromosomal abnormalities (“clonal evolution”)

What is the blast crisis phase of CML?

aggressive disease, BM blasts >20%, essentially conversion to AML

What is the goal of therapy in CML?

control disease in the chronic phase and prevent progression to blast crisis (AML)

Is CML curable?

no (except for allogeneic transplant) but it is highly controllable

What revolutionized treatment for CML?

the discovery of Philadelphia chromosome and the creation of BCR-ABL tyrosine kinase inhibitors

What tyrosine kinse inhibitors (TKIs) are used for CML?

Imatinib (Gleevec)- first class

Dasatinib (Sprycel)- 2nd generation

What is a leukemoid reaction?

elevated WBC (like leukemia) but due to a prolonged, severe infection

WBC >50,000 w/ predominante of neutrophils and bands, but NO blasts or Philadelphia chromosome are present

difference between leukemia and lymphoma

leukemia- when present in large numbers in blood/marrow, can affect organs; originates from blasts

lymphoma- localized in lymphoid tissue; originates from mature lymphocytes

Lymphoid neoplasms form from a malignant transformation of what cells?

B cells, T cells, and NK cells

What is the most common childhood malignancy?

acute lymphoblastic leukemia (ALL)

Are outcomes of ALL better in children or adults?

children

What are the two peak of incidences of ALL?

children under 5 and adults over 50

fWhat are the acute onset sx of ALL?

fever, fatigue, inc infections, increased. bleeding/bruising, focal neurologic deficits/seizures due to CNS involvement

What are physical exam findings of ALL?

petechiae, pallor, splenomegaly, hepatomegaly, LAD

What would you see on a CBC in an ALL patient/

marked anemia, neutropenia, thrombocytopenia, blasts on differential, kidney injury

in a bone marrow biopsy on an ALL patient, what would you see a >20% increase in?

lymphoblasts

What do both adult and pediatric treatment regimens include in ALL?

CNS prophylaxis due to high prevalence of CNS disease

pediatric tx for ALL

intensive combination chemotherapy given sequentially over 2-3 years (female- 2 years, male- 3 years)

stem cell transplant reserved for relapsed/refractory disease

adult tx for ALL (and why is it different than pediatrics)

combination therapy (can’t tolerate the heavy tx kids receive)

stem cell transplant reserved for those w/ good performance status to be able to tolerate the treatment

What is the most common leukemia overall?

CLL

What is the difference between CLL and SLL?

same disease but:

CLL- disease cells in peripheral circulation

SLL- disease cells form solid masses in lymph nodes

What leukemia is a neoplastic transformation of the mature B-lymphocyte?

CLL

What is the median age at diagnosis of CLL?

71 (disease of the elderly)

What is the clinical presentation of CLL?

fatigue, LAD, hepatomegaly, splenomegaly, or asx (discovered on incidental CBC)

What do you see on a CBC for CLL?

inc absolute lymphocyte count (ALC)

lymphocytosis >5,000

± anemia, thrombocytopenia

what is seen on a peripheral smear for CLL?

smudge cells- fragile B-lymphocytes break as a result of smear creation

What do you see in a BM bx for CLL?

predominance of mature lymphocytes

How is CLL staged?

Rai system (more common in US) and Binet system (more common in Europe)

utilizes LAD, splenomegaly, and cytopenias to determine prognosis

The prognosis of CLL depends on chromosomal abnormalities. What would result in a very poor prognosis?

deletion of 11 or 17p oncogene

What is the tx regimen for CLL?

“watch and wait” active surveillance; initiate tx only when disease causes sx

When a CLL patient is having sx, what is the tx?

chemo-immunotherapy and allogeneic stem cell transplant (reserved for aggressive disease in younger patients)

What are the chemo-immunotherapy drugs used for CLL tx?

fludarabine/chlorambucil/rituxan (FCR)- young fit patients

Ibrutinib- oral, targeted agent, improved prognosis of 17p deletion

What is 30% of all malignant lymphomas?

hodgkin lymphoma

What are the 2 primary subtypes of Hodgkin lymphoma?

classical and lymphocyte predominant

What is the bimodal age distribution of Hodgkin lymphoma?

15-30 years and >50 years

What virus is associated w/ up to 40-505 of cases of Hodgkin lymphoma?

EBV (also known association w/ HIV)

What is the clinical presentation of Hodgkin lymphoma?

asymptomatic lump, B-symptoms, pruritus, pain on drinking alcohol, LAD (usually cervical initially), leukocytosis/eosinophilia

What are the B-symptoms associated w/ Hodgkin lymphoma?

fever, night sweats, weight loss

generally correlates w/ slightly worse prognosis and decreased survival rate

Evaluation of Hodgkin lymphoma

excisional bx (core needle usually not and FNA definitely not sufficient for pathology)

CBC, ESR/LDH, PET or CT of neck, chest, abdomen, and pelvis, BM bx if advanced

pathology of Hodgkin lymphoma

reed-sternberg cells surrounded by healthy reactive cells; presentation in a single node initially, typically spreads in contiguous pattern

What are reed-sternberg cells?

large, bi nucleate pathologic cell w/ “owls eye” appearance; seen in Hodgkin lymphoma

What staging system does Hodgkin lymphoma use?

modified Ann Arbor

what is the tx for hodgkin lymphoma?

chemo: ABVD X 6 cycles

± XRT (radiation therapy)

brentuximab vedotin monoclonal ab against CD30 (new drug)

autologous transplant for relapsed/refractory dz

(consider allogeneic or immunotherapy Nivolumab if transplant fails)

What is the risk with ABVD tx for hodgkin lymphoma? what is needed prior to starting tx?

cardio and pulmonary toxicity —> need ECHO and PFT’s prior to starting

What is the origin of 95% of non-hodgkin lymphoma (NHL)?

B-cell

What ages are the peak incidence of NHL?

20-40

What are the classifications of non-hodgkin lymphoma NHL?

indolent: “watch and wait” if no sx (CLL/SLL, follicular lymphoma)

intermediate (DLBCL)

aggressive (burkitt lymphoma, ALL)

what is the clinical presentation of NHL?

painless enlargement of lymph nodes

B symptoms (fever, night sweats, wt loss)

advanced- SVC syndrome, airway obstruction, cord compression, gastric outlet obstruction