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AHN 554 > Leukemias > Flashcards

Leukemias Flashcards

1
Q

Acute lymphocytic leukemia (ALL) definition

A

MAlignancy that causes hematopoietic progenitor cells to lose their ability to mature normally and differentiate

cells proliferate in uncontrolled fashion and ultimately replace normal bone marrow leading to decreased production of normal RBC, WBC, and platelets

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2
Q

Incidence/predisposing factors

A
  • no clear cause, greater incidence with benzene and petroleum product exposure
  • more common in European descent
  • cause of 80% of childhood cancers, peak age 3-7 years, and 20% of adult cancers peak age 60
  • most common cancer and leading cause of death in children under 15
  • survivors of ALL at risk for late sequelae of secondary brain tumors
  • childhood survivors at greater risk for reduced growth, learning disabilities, and osteoporotic fxs later in life
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3
Q

S&S of ALL

A

sudden onset of acute illness for days or weeks, fever, anorexia, fatigue, bone/joint pain, sob, gum hypertrophy and bleeding, nose bleeds, chest pain, pale, purpura, petechiae, lymphadenopathy, stomatitis, hepatosplenomegaly, bone tenderness ESPECIALLY sternum and tibia

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4
Q

lab hallmark of ALL

A

pancytopenia with circulating blasts, blast cells on 90 % of smears

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5
Q

Bone marrow in ALL

A

usually hypercellular, diagnosis requires that more than 30% of cells are blasts,

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6
Q

ALL blood work

A

decrease in RBCs, hemoglobin, hematocrit, and platelets, elevated urea (azotemia), terminal deoxynucleotidyl transferase present in 95% of cases

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7
Q

test needed confirm ALL diagnosis

A

bone marrow biopsy

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8
Q

cytogenic studies for ALL

A
  • Hyperdiploid states: more favorable prognosis

- Philadelphia (pH) chromosome t(9,22) and (4/11): unfavorable prognosis

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9
Q

Bone marrow stains for ALL (4)

A

Periodic acid sschiff: positive
Terminal deoxynucleotidyl transferase: Positive

Sudan black: negative
Myeloperoxidase: negative

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10
Q

Tests to consider for ALL

A

chromosome analysis, multiparametric flow cytometry (relapse prediction), molecular genetic studies, lumbar puncture

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11
Q

Manamagent for ALL

A
  • hematology/oncolgy consult
  • supportive tx or eradication of mass
  • stem cell transplant is goal (cures not common except in children
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12
Q

ALL survival rates

A

25% remain disease free, 5 year survival w/o aggressive tx

35-40% remain disease free, 5 year survival with aggressive tx

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13
Q

supportive care for ph positive ALL patients

A
  • tyrosine kinase inhibitor will be induction therapy:
  • transfusion of RBCs and platelets
  • hydration
  • aggressive antibiotic therapy for infection
  • allopurinol to prevent renal damage and hyperuricemia BEFORE chemo
  • acetazolamide to make urine alkaline
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14
Q

Before chemo what do you for uremic ALL patients

A

start dialysis

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15
Q

Chemotherapy phases for ALL

A

Divide into 3 phases:
Remission Induction
Post remission therapy consolidation
CNS prophylaxis

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16
Q

Remission induction therapy for ALL

A
  • Initial tx: combo chemo and TKI if ph positive or clinical trial
  • TKIs: *vincristine, prednisone, cyclophosphamide, doxorubicin, dexamethasone, cytarabine, methotrexate, imatinib, dasatinib
  • intrathecal methotrexate with 1 asparaginase in ; intrathecal methotrexate + cytarabine + corticosteroids
  • maintenance therapy is 6 mercaptopurine and methotrexate
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17
Q

Post remission ALL

A
  • Short courses of further chemo given
  • daily 6-mercaptopurine, weekly methotrexate, TKIs in Ph positive patients with nelarabine preferred in refractory t cell ALL
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18
Q

CNS prophylaxis in ALL

A

intrathecal methotrexate alone or in combination with radiation

**CNS relapse much higher in ALL than AML

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19
Q

When to consider bone marrow transplant for ALL

A

at time of 1st relapse or 2nd remission

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20
Q

Acute Myeloid Leukemia (AML) definition

A
  • malignancy of hematopoietic progenitor cells
  • similar to AML, but distinguished by morphologic examination and cytochemistry that differentiates myeloblasts from lymphoblasts
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21
Q

Classifications of AML (4)

A
  • AML with recurrent genetic abnormalities
  • AML with multilineage dysplasia
  • Therapy related AML
  • AML not otherwise categorized
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22
Q

Bone marrow or peripheral blood blast % needed to diagnosis AML

A

20%

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23
Q

Incidence/predisposing factors

A
  • no clear cause
  • increased incidence in patients with chromosomal abnormalities, especially Down syndrome
  • Predominant type of acute leukemia in adults: 80% in adults over 20
  • incidence increases with age: median 67 years old
  • increased incidence of DIC
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24
Q

S&S of AML

A

bleeding, SOB, bruising, fever, anorexia, weight loss, HA, bone and joint pain, bone tenderness (sternum and tibia), exposure to petrochemicals and/or ionizing radiation, lymphadenopathy, hepatosplenomegaly, stomatitis, gingival hypertrophy, purpura, petechiae, overt bleeding, infection

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25
Q

labs in AML

A
  • pancytopenia, anemia,
  • low RBCs, hgb, hct, and platelets
  • mild thrombocytopenia
  • granules in blast cells
  • Auer rods
  • Myeloblasts
  • butyrate esterase
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26
Q

Why are AML patients prone to DIC

A

elevated PT, PTT, fibrin degredation products, and d dimer, decreased fibrinogen

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27
Q

prognosis findings with Immunophenotyping in AML

A

Favorable: t(8,21), t(15,17), and inv(16)(p13,q22)
Unfavorable: monosomy 5 and 7 and complex abnormalities

28
Q

Bone marrow stain results in AML

A

Sudan black: positive

Myeloperoxidase: positive

29
Q

main AML tx

A
  • hematology/oncology consult

- chemo, radiation, stem cell transplant, targeted immune therapy

30
Q

AML supportive tx

A
  • transfuse of RBCs and platelets
  • hydration
  • aggressive antibiotic therapy for infection
  • acetazolamide, to create alkaline urine
  • allopurinol, to prevent hyperuricemia and renal damage
31
Q

Remission induction combo chemotherapy AML

A
  • dose intensive cytarabine
  • cytarabine and daunorubicin
  • cytarabine and idarubicin
  • cytarabine and daunorubcin and thioguanine/cladribine
  • mitoxantrone and etopside, cytarabine and daunorubicin and 5-azacytidine
  • treat CNS leukemia with intrathecal cytarabine or methotrexate
32
Q

Consolidative and maintenance therapy for AML

A
  • cytarabine based combo if tolerated
  • mitoxantrone and daunorubicin
  • mitoxantrone and idarubicin
  • high dose ARA-C
  • M3 subtype initiated with retinoic acid then use above meds
33
Q

When to use bone marrow transplant in AML

A

consider at time of 1st relapse or second remission (salvage therapy), Consider after induction therapy and each surveillance visit or change of tx visit

34
Q

Chronic Lymphocytic Leukemia (CLL) definition

A

chronic leukemia with abnormal b lymphoctyes, generalized lymphadenopathy

if blood and bone marrow involvement its call CLL

in those with enlarge lymph nodes, its called small lymphocytic lymphoma

35
Q

CLL incidence/predisposing factors

A

-most common leukemia in adults, especially elderly. 90% of patients are >50 years old, median age 65

  • slow progressing dz, origin unknkown
  • 1st degree relatives are 3 x more likely to get CLL
  • more common in russian and eastren european jewish descent
  • more common in farmers, men
  • associated with warm antibody autoimmune hemolytic anemia
  • median survival 6 years
36
Q

S&S of CLL

A
  • asymptomatic
  • fatigue, malaise, lethargy, anorexia, progressive weight loss, early satiety, lymph node enlargement (painless), pain or feeling of fullness below the ribs
  • fever is RARE
  • strong reaction to insect bites
  • lymphadenopathy: usually cervical, supraclavicular, and axillary; usualy mobile and nontender with rubbery feel
  • hepatosplnomegaly
37
Q

Hallmark lab finding for CLL

A

Lymphocytosis
minimal level >5000
usual range 40,000-150,000
lymphocytes are 75% to 98% of circulating cells

38
Q

peripheral smear findings for CLL

A

smudge cells

39
Q

immunoglobulins in CLL

A

hypogammaglobinemia

-IgG, IgA, IgM levels are low

40
Q

lymphocytes specific to CLL

A

B lymphocyte lineage marker CD19 with T lymphocye marker CD5

41
Q

Bone marrow results CLL

A

more than 30% lymphocytes seen
focal or diffuse infiltration
extent of marrow infiltration correlates with severity of disease

42
Q

Rai system stages (5)

A 
Stage 0: lymphocytosis only
Stage 1: lymphocytosis plus lymphadenopathy 
Stage 2: organomegaly 
Stage 3: anemia
Stage 4: thrombocytopenia
43
Q

CLL management

A

consult hematology/oncology

  • therapy not initiated until symptoms occur
  • chemo given according to staging and presence or absence of deletions at 11 q and 17 p
  • chemo combined with targeted therapy drug (usually monoclonal antibody) and/or an immunotherapy
44
Q

chemotherapy if younger than 70 for CLL

A
  • FCR: fludarabine, cyclophosphamide, rituximab
  • FR: fludarabine, rituximab
  • PCR: pentostatin, cyclophosphamide, rituximab
  • Bendamustine with rituximab
  • consider stem cell transplant after induction for those under 65 year
45
Q

chemo of older than 70 for CLL

A

chlorambucil and rituximab
bendamustine and rituximab
alemtuzumab
lenalidomide

46
Q

which med does clinical guidelines say is best for higher response rate and lasting results for CLL

A

fludarabine

47
Q

Stages and survival for CLL

A

Stage 0-1 disease median 10-15 years

Stage 3 and 4 median survival 2 years

48
Q

Radiation for CLL

A

usually used for localized nodule masses that are refractory to chemo

49
Q

Supportive care for CLL

A

flu shot
pneumo shot q 5 years
avoid live vaccines and zooster

50
Q

Chronic Myelogenous Leukemia (CML) definition

A

disorder characterized by myeliod cell production

  • abnormal cells overcome and replace normal hematopoiesis
  • clonal stem cell disorder
  • Philadelphia chromosones in leukemia cells translocated pieces fuse the gene BCR/ABL protein leading to leukemia
51
Q

Chromosome linked specifically to CML

A

Philadelphia chromosome

52
Q

Incidence/predisposing factors CML

A
  • 7-15% of adult leukemias
  • primarily disorder of middle age (median age 67)
  • radiation exposure increases risk
  • atomic bomb survivors have increased incidence 5-10 years after exposure
  • unknown cause
  • no significant hereditary link
  • medican survival rate 3-4 years but may go into remission in 4 years with aggressive tx with TKI
53
Q

S&S of early CML

A

insidious onset, fatigue, early satiety, weight loss, diminished exercise tolerance,

54
Q

S&S of progression of CML

A

low grade fever, dizziness, irritability, increased sweating/night sweats, abdominal fullness, bone pain, blurred vision, resp distress, splenomegaly, , bone pain/sternal tenderness, hepatomegaly, bleeding and infection with blast crisis

55
Q

Hallmark lab of CML

A

WBCs elevated, blasts usually <5%

BCR/ABL gene dectected with use of polymerase chain reaction

56
Q

Labs of CML

A
  • HGB and HCT normal and decrease with progression
  • platelets up at the beginning then drop with progression
  • B12 elevated
  • LDH and uric acid elevated
  • Philadelphia chromosome present
  • low to absent leukocyte, less than 22
57
Q

Management of CML

A

Hematology/oncology referral

-no therapy until WBC < 200,000 or evidence of priaprism, confusion, DVT, visual blurring, SOB

58
Q

Best TKI for CML

A

imatinib for BCR/ABL

59
Q

If imatinib fails, what is second line for CML

A

nilotinib or bosutinib

60
Q

3rd line tx for CML

A

omacetaxine

61
Q

Last resort for CML

A

hematopoietic stem cell transplant

62
Q

Support therapy for CML

A
  • hydration
  • allupurinol (hyperuricemia)
  • hydroxyurea or apharesis for leukocytosis
  • TKI
  • hydroxyurea, anti aggregants, anagrelide, or apharesis for thrombocytosis
63
Q

Treatment length and intervals for CML

A

Treatment with TKI at month 3 and 6, then every 6 months after that

64
Q

Drug that alter therapeutic effects of TKIs

A

drugs that induce or inhibit CYP3A4 (Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, a) and CYP3A5 (Cobicistat) enzyemes

65
Q

only curative therapy for CML

A

allogenic bone marrow transplant (from sibling)

BUT there is 40% change of death in the 1st year due to adverse effects of transplant

AHN 554 (13 decks)

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