Clin Med II Exam 2 - HEME (LEUKEMIAS)

gbalsam

leukemia

malignant hematologic disorder characterized by a proliferation of abnormal white cells that infiltrate the bone marrow and organs

pancytopenia

deficiency of all types of blood cells (neutropenia, anemia, and bleeding from thrombocytopenia)

progression of acute leukemia

quick

acute leukemia

characterized by the proliferation of undifferentiated cells in the bone marrow (blasts) causing increased infection as immature WBCs are incapable of fighting & reduced bone marrow ability to produce normal cells

progression of chronic leukemia

slow

chronic leukemia

uncontrolled expression of mature cells

myelogenous leukemia

those that are from hemopoietic stem cells (usually causing an overgrowth of myeloblasts)

lymphocytic leukemia

arise from the lymphocytic line in the bone marrow

general symptoms of leukemia

- leukemic cells accumulating in bone marrow hampering the production of normal blood cells

- anemia, thrombocytopenia, neutropenia all causing fatigue, pallor, bleeding, increased infections

general signs of leukemia

- non-tender lymphadenopathy in the neck, supraclavicular are, and axilla (cervical adenopathy in 80-90% of cases)

- mediastinal adenopathy (more than 50% at diagnosis)

- prone to infections (i.e., herpes zoster in 1/4th of patients and fungal or mycobacterial infections)

French-American-British leukemia classification (AML)

AML M0-M7

French-American-British leukemia classification (ALL)

ALL L1-L3

acute lymphocytic leukemia (ALL)

the most common pediatric cancer

etiology of ALL

unknown with some hereditary and environmental factors

patho of ALL

characterized by the uncontrolled proliferation of lymphoblasts limiting the production of other cells by overcrowding and inhibiting cell growth/differentiation

subtypes of ALL

- B-cell

- T-cell

- null type

clinical presentation of ALL

present with symptoms related to anemia, leukopenia (neutropenia), and thrombocytopenia

~ fatigue, pallor, bruising, bleeding, infections

other common symptoms of ALL

- liver, splenic, and testicular enlargement in males

- anorexia, weight loss, abdominal distention or pain, or an abdominal mass

- may mimic RA with swollen joints, bone pain, and tenderness causing a child to limp or not walk

- vomiting, headaches, papilledema (vision changes), neck stiffness, and cranial nerve palsy

when do symptoms typically occur in ALL?

rarely more than 6 weeks before diagnosis

cervical adenopathy in ALL

one of the indications of extramedullary leukemic spread

what is an enlarged lymph node?

>10 mm in its greatest diameter

what is an enlarged epitrochlear lymph node?

>5 mm

what is an enlarged inguinal lymph node?

>15 mm

what is an enlarged cervical lymph node?

>20 mm

characteristics of malignant lymphadenopathy

non-tender, firm, rubbery, and matted

WBC counts in ALL

varies from 5-100 thousand

what would indicate a poorer prognosis in ALL?

an abnormal increase in WBC

immunophenotyping

morphological evaluation, special stains, electron microscopy, and surface markers establish diagnosis of ALL in about 90% of cases

gold standard for diagnosing ALL

bone marrow biopsy

bone marrow biopsy of ALL

hypercellular, >20% lymphoblasts

indications for bone marrow biopsy

- atypical cells in the peripheral blood

- unexplained depression of more than one peripheral blood element (cytopenias)

- unexplained lymphadenopathy or hepatosplenomegaly associated with cytopenias

what are the two most common sites for extramedullary leukemia?

CNS and testes

staging of ALL

FAB: classified according to cell size, nuclear shape, number of nuclei, prominence of nuclei, and amount of cytoplasm (L1, L2, and L3)

WHO: cytogenic, molecular, and immunophenotype information (precursor B or precursor T)

acute treatment of ALL

- emergency treatment (ABCs)

- radiation therapy

- 3 stages of chemo based on protocol (induction, consolidation, and maintenance)

- bone marrow transplant

what is the treatment of choice for ALL, AML, and CML?

bone marrow transplant

induction stage of chemotherapy

trying to get the abnormal cells to be as active and as abnormal as possible to easily differentiate before treatment

transient complications of total body irradiation (TBI) in ALL

- GI (nausea, vomiting, diarrhea, anorexia, and malaise)

- mucosa of the mouth, pharynx, bladder, and rectum may be affected

- skin reactions, alopecia, interstitial pneumonitis

- decreased blood counts

chronic complications of total body irradiation (TBI) in ALL

- permanent sterility

- cataracts

- hepatic fibrosis and radionecrosis of genital tissue, muscle, and kidney

- secondary malignancy (esp. lymphoma)

- lung and heart problems

- retarded growth

poorer prognosis of ALL based on age

- children <2 and >10 years old

- children <1 year old

- any adult (specifically >50 years old)

poorer prognosis of ALL based on WBC

- initial count of <10,000

- count of >50,000

classic presentation of ALL

lymphadenopathy + bone pain + bleeding + fever in a child

acute myelogenous leukemia (AML)

occurs 5x greater than ALL as it can occur at any age

etiology of AML

idiopathic

patho of AML

proliferation of precursor cells that have lost the ability to differentiate resulting in the gradual accumulation of undifferentiated cells in marrow or other organs

signs/symptoms of AML

- increasing fatigue or decreased exercise tolerance

- excessive bleeding

- fevers or recurrent infections

- headache, vision changes, confusion, TIA

- early satiety

- history of cancer

- abrupt onset

- similar symptoms to ALL

- increased susceptibility due to neutropenia

- respiratory distress or dyspnea

diagnosis of AML

>20% myeloblasts from bone marrow biopsy

what might you see on a peripheral blood smear in diagnosing AML?

Auer rods

Auer rods

structures in the cytoplasm of myeloblasts, myelocytes, and monoblasts

staging of AML

FAB is used for morphological evaluation; maturation states are categorized from M0 (undifferentiated) to M7 (megakaryocyte)

AML M0

minimally differentiated acute myeloblastic leukemia

AML M1

acute myeloblastic leukemia without maturation

AML M2

acute myeloblastic leukemia with granulocytic maturation

AML M3

promyelocytic or acute promyelocytic leukemia (APL)

AML M4

acute myelomonocytic leukemia

AML M4eo

acute myelomonocytic leukemia with bone marrow eosinophilia

AML M5

acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b)

AML M6

acute erythroid leukemias, including erythroleukemia (M6a) and pure erythroid leukemia (M6b)

AML M7

acute megakaryoblastic leukemia

acute treatment of AML

combination of chemotherapy and bone marrow transplant

leukostasis management in AML

leukapheresis or chemotherapy

tumor lysis syndrome

potentially lethal side effect to chemotherapy initiation due to the large number of cells being destroyed leading to hyperuricemia, increased potassium, decreased calcium, increased phosphate, and acute renal failure

prognosis of AML based on WBC count

- <20,000 most favorable

- 20,000-49,000 in the middle

- >50,000 worst prognosis

unfavorable prognosis of AML

- >50 years old

- poor performance status

- low serum albumin

classic presentation of AML

blasts + Auer rods + adult patient

chronic lymphocytic leukemia (CLL)

most common leukemia in Western countries

etiology of CLL

hereditary factors with possible links to immunodeficiency syndromes and viruses

patho of CLL

increased number of leukemic cells in bone marrow, blood, lymph nodes, spleen, resulting in an enlarged spleen and decreased bone marrow function

what is the most common chromosomal abnormality seen in CLL?

deletion at 13q14

signs/symptoms of CLL

- new lymphadenopathy

- fatigue

- dyspnea on exertion

- frequent infections

- bone pain

- excessive sweating

- generalized itching

- easy bruising

- lymphadenopathy

- spleno/hepatomegaly

- lymphocytosis

CLL peripheral blood smear

well-differentiated lymphocytes with scattered "Smudge cells"

Smudge cells

fragile B-cells that often smudge during slide preparation

immunophenotyping in CLL

- CD5 and CD23 markers

- >30% CD38 marker (worse prognosis)

Rai's staging system (stage 0)

low risk

Rai's staging system (stages I and II)

intermediate risk

Rai's staging system (stages III and IV)

high risk

staging of CLL

based on presence of adenopathy, splenomegaly, anemia, and thrombocytopenia

Binet staging of CLL

based on the involvement of cervical nodes, axillary nodes, inguinal nodes, spleen, and liver

CLL subtypes

B-cell or T-cell

CLL Rai stage 0

over 10,000 lymphocytes of blood (some doctors will diagnose if the count is over 5,000 and the cells have the same chemical pattern)

CLL Rai stage I

lymphocytosis plus enlarged lymph nodes

CLL Rai stage II

lymphocytosis plus an enlarged spleen (and possibly liver), with or without enlarged lymph nodes

CLL Rai stage III

lymphocytosis plus anemia, with or without enlarged lymph nodes, spleen, or liver; platelet counts near normal

CLL Rai stage IV

lymphocytosis plus thrombocytopenia, with or without anemia, enlarged lymph nodes, spleen, or liver

treatment of CLL

- observation in an early stage patient

- PO chemotherapy used to treat anemia, thrombocytopenia

- treat acute blastic crisis like AML

- radiation used palliatively for localized tumors of lymph tissue

- possible splenectomy

what do patients with CLL most often die from?

infection or bone marrow failure

classic presentation of CLL

middle age patient + blasts + Smudge cells on peripheral smear

chronic myelogenous leukemia (CML)

abnormal hematopoietic stem cells that contain the Philadelphia chromosome (present in >95% of cases)

patho of CML

linked to radiation and benzene exposure

three stages of CML

- chronic phase

- accelerated phase

- blast crisis

early clinical presentation of CML

- malaise, fatigue, sweating, intolerance to heat, easy bruising, and weight loss

- splenomegaly

- early satiety, weight loss, peripheral leg edema

blast crisis of CML

occurs about 3-4 years after diagnosis

clinical presentation of CML blast crisis

all organs invaded by the leukemic blast cells resulting in fever, bone pain, and weight loss

clinical presentation of active CML

- weight loss (>10% in <6 months)

- fever

- extreme fatigue

- anemia, thrombocytopenia

- organ involvement (other than lymph nodes, spleen, liver, and bone marrow)

- progressive or painful enlargement of spleen

most important diagnostic indicator of CML

presence of Philadelphia chromosome

diagnosis of CML chronic phase

<5% blasts

diagnosis of CML accelerated phase

>5-30% blasts

diagnosis of CML blast crisis

>20% blasts when accompanied by fever, malaise, and progressive splenomegaly

CML disease acceleration

- increasing anemia

- blood or marrow blasts between 10 and 20%

- blood or marrow basophils >20%

- platelet count <100,000

treatment of Philadelphia-positive CML

- PO chemotherapy (Imatinib, hydroxyurea)

- radiation

- chemotherapy

- stem cell transplant

classic presentation of CML

adult patient + strikingly increased WBC count (>100,000) + hyperuricemia + Philadelphia chromosome