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WILLIAM'S HEMATOLOGY > 87 Acute Myelogenous Leukemia > Flashcards

87 Acute Myelogenous Leukemia Flashcards

1
Q

4 environmental factors are established causal agents of AML

A

high-dose radiation exposure
chronic, high-dose benzene exposure (≥40 parts per million [ppm]-years)
chronic tobacco smoking
chemotherapeutic (DNA-damaging) agents

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2
Q

An endogenous factor that increases risk is obesity. Studies in North America show an increased risk of AML in men and women with elevated body mass index, and this is particularly notable for __________________

A

Acute promyelocytic leukemia (APL)

The precise mechanisms are still unclear but may be related, in part, to

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3
Q

The most compelling data indicate that the bulk of AML cases arise from 1 of 2 predominant CD34+ cell populations:

A

CD34+CD45RA+CD38−CD90− (multipotential myeloid progenitor)

or

CD34+CD38+CD45RA+CD110+ (granulocyte–monocyte progenitor)

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4
Q

Chromosome changes involving CBF

A

t(8;21), inv(16), t(16;16), or t(15;17)

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5
Q

Increased in frequency in patients over 60 years of age and in cases that develop after cytotoxic therapy

A

Deletions in chromosome 5 and 7 and complex cytogenetic abnormalities

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6
Q

Mutations with favorable outcomes

A

t(8;21)(q22;q22.1)
RUNX1-RUNX1T1
inv(16)(p13.1q22) or t(16;16)(p13.1;q22)
CBFβ-MYH11
Mutated NPM1 without FLT3-ITD or with
FLT3-ITDlow
Biallelic mutated CEBPa

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7
Q

Mutations with poor outcome

A

t(6;9)(p23;q34.1)
DEK-NUP214
t(v;11q23.3)
KMT2A rearranged
t(9;22)(q34.1;q11.2)
BCR-ABL1
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)
GATA2,MECOM(EVI1)
−5 or del(5q); −7; −17/abn(17p)
Complex karyotype, monosomal karyotype
Wild-type NPM1 and FLT3-ITDhigh
Mutated RUNX1or ASXL1 without good risk
karyotype
Mutated TP53

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8
Q

TRUE OR FALSE

Patients with CBF leukemias expressing KIT have a good prognosis.

A

FALSE

Patients with CBF leukemias expressing KIT have a worse prognosis.

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9
Q

TRUE OR FALSE

A monosomal karyotype is associated with a decreased chance of achieving remission or survival, especially when combined with TP53 mutations.

A

TRUE

A monosomal karyotype is associated with a decreased chance of achieving remission or survival, especially when combined with TP53 mutations.

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10
Q

Approximately _______of AML cases have a normal karyotype

A

45%

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11
Q

Most frequently mutated gene in AML (50%)

Allogenic transplantation not needed in first
remission if this mutation occurs in absence
of mutated FLT3-ITD

A

NPM1

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12
Q

An ITD of FLT3 on chromosome 13 occurs in approximately ____ of adult AML cases

A

25%

FLT3-ITD expression is often higher at relapse.

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13
Q

The FLT3-ITD mutation confers a poor prognosis if the ratio of mutant to wild-type expression is (LOW/HIGH).

A

high (≥0.51)

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14
Q

TRUE OR FALSE

Point mutations in the ITD of FLT3 mutations occur in approximately 6% of AML cases and have little impact on outcomes.

A

FALSE

Point mutations in the TKD of FLT3 mutations occur in approximately 6% of AML cases and have little impact on outcomes.

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15
Q

A leucine zipper transcription factor involved in myeloid differentiation.

A

CEBPα

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16
Q

TRUE OR FALSE

CEBPα-double, but not CEBPα-single, mutation patients had a significantly better overall survival at 8 years than wild-type, CEBPα-single, or CEBPα-double and FLT3-ITDpositive patients.

A

TRUE

CEBPα-double, but not CEBPα-single, mutation patients had a significantly better overall survival at 8 years than wild-type, CEBPα-single, or CEBPα-double and FLT3-ITDpositive patients.

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17
Q

Catalyze oxidative decarboxylation of isocitrate into α-hemoglutarate

A

IDHs

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18
Q

Found to predict for the presence of IDH1/IDH2 mutations

A

Serum 2hydroxyglutarate

A level of 700 ng/mL was found to discriminate mutated from nonmutated

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19
Q

The detection of persistent leukemia-associated mutations in at least ______% of marrow cells in day 30 remission marrow cell samples is associated with a high risk of relapse.

A

5%

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20
Q

AML is the predominant form of leukemia during the: (Neonatal OR childhood OR adolescence)period

A

Neonatal period

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21
Q

AML is more common in (males/females)

A

Males

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22
Q

The acute promyelocytic variant of AML is somewhat more common in __________ (race)

A

Latinos

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23
Q

CD11b, CD13, CD15, CD33, CD117,
HLA-DR

A

Myeloblastic

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24
Q

CD11b, CD13, CD14, CD15, CD32, CD33,
HLA-DR

A

Myelomonocytic

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25
Q

Glycophorin, spectrin, ABH antigens,
carbonic anhydrase I, HLA-DR, CD71
(transferrin receptor)

A

Erythroid

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26
Q

CD13, CD33

A

Promyelocytic

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27
Q

CD11b, 11c, CD13, CD14, CD33, CD65,
HLA-DR

A

Monocytic

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28
Q

CD34, CD41, CD42, CD61, anti–von
Willebrand factor

A

Megakaryoblastic

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29
Q

CD11b, CD13, CD33, CD123, CD203c

A

Basophilic

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30
Q

CD13, CD33, CD117

A

Mast cell

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31
Q

Palpable splenomegaly or hepatomegaly occurs in approximately ______of patients.

A

25%

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32
Q

Lymphadenopathy is extremely uncommon, except in the ______________ variant of AML

A

Monocytic variant of AML

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33
Q

Extramedullary involvement is most common in____________________leukemia.

A

Monocytic or myelomonocytic leukemia

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34
Q

Skin involvement in AML may be of 3 types:

A

Nonspecific lesions
Leukemia cutis
Granulocytic (myeloid) sarcoma of skin and subcutis

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35
Q

A necrotizing inflammatory lesion involving the terminal ileum, cecum, and ascending colon, can be a presenting syndrome or occur during treatment

A

Ileotyphlitis (enterocolitis)

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36
Q

A tumor composed of myeloblasts, monoblasts, or megakaryocyes

A

Myeloid sarcoma

Synonyms: granulocytic sarcoma, chloroma, myeloblastoma, monocytoma

The tumors originally were called chloromas because of the green color i

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37
Q

Most frequent cytogenetic disturbance in myeloid sarcomas

A

Abnormalities in chromosome 8

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38
Q

(Systemic chemotherapy or local therapy), should be used for treatment of myeloid sarcoma, although the long-term outcome in such cases usually is poor.

A

Systemic chemotherapy

Systemic chemotherapy, rather than local therapy, should be used for tre

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39
Q

Mutations with propensity to develop extramedullary leukemia

A

AML with t(8;21) or inv16

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40
Q

Principal cause of anemia in AML

A

Inadequate production of red cells

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41
Q

Mechanism of thrombocytopenia in AML

A

Inadequate production and decreased survival of platelets

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42
Q

Are elliptical cytoplasmic inclusions, approximately 1.0–1.5 μm long and 0.5 μm wide, that derive from azurophilic granules

A

Auer rods

APL: higher proportion of cells have Auer rods and some have multiple (b

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43
Q

The WHO has invoked an arbitrary threshold of______of marrow nucleated cells being blast cells to distinguish polyblastic AML from oligoblastic myelogenous leukemia

A

20%

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44
Q

Relapse of AML can be identified as any increase in blast count greater than _______

A

2%

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45
Q

TRUE OR FALSE

Any distinctions between MDS and AML in survival are a function of age, cytogenetic risk category, and molecular features, and the blast count.

A

FALSE

Any distinctions between MDS and AML in survival are a function of age, cytogenetic risk category, and molecular features, not the blast count.

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46
Q

Myeloblasts are distinguished from lymphoblasts by any of 3 pathognomonic features:

A
  • Reactivity with specific histochemical stains
  • Auer rods in the cells
  • Reactivity with a panel of monoclonal antibodies against epitopes present on myeloblasts (eg, CD13, CD33, CD117)
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47
Q

Leukemic myeloblasts give positive histochemical reactions for:

A

Myeloperoxidase, Sudan black B, or naphthyl AS-D-chloroacetate esteras

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48
Q

Blast cells may express :

Granulocytic surface antigens __________________ or
Monocytic surface antigens _____________

A

Granulocytic surface antigens (CD15, CD65) or
Monocytic surface antigens (CD11b, CD11c, CD14, CD64)

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49
Q

AML associated with intense fibrosis

A

Megakaryoblastic leukemia

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50
Q

Associated with marrow basophilia

A

t(6;9)

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51
Q

Associated with marrow eosinophilia

A

inv16 or t(16;16)

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52
Q

Associated with in cases of AML following chemotherapy or radiotherapy

A

Loss of part or all of chromosomes 5 and 7

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53
Q

Chromosome abnormality very common in acute myeloblastic leukemia

A

Trisomy 8

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54
Q

t(9;22) (q34; q22) in BCR-ABL1 gene is present in ______ of patients with AML

A

~2%

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55
Q

Often acute myelomonocytic phenotype; associated with increased marrow
eosinophils; predisposition to cervical lymphadenopathy, better response to
therapy

A

Inv(16) (p13.1;q22) or
t(16;16) (p13.1;q22)

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56
Q

~1% of cases of AML

Approximately 85% of cases with normal or increased platelet count

Marrow has increased dysmorphic, hypolobulated megakaryocytes.

Hepatosplenomegaly more frequent

A

Inv(3) (q21q26.2) /RPN1-EVI1

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57
Q

Approximately ______% of cases of AML contain cells that are cytogenetically normal.

A

45%

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58
Q

Serum uric acid and lactic dehydrogenase levels are higher in___________________AML than in other AML phenotypes

A

Myelomonocytic and monocytic AML

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59
Q

Are associated with hypofibrinogenemia and other indicators of activation of coagulation or fibrinolysis

A

APL and acute monocytic leukemia

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60
Q

Hyperleukocytosis is a markedly elevated blood blast cell count, usually greater than _____________

A

100 × 10 9 /L

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61
Q

Subsets of AML are associated with a greater likelihood of presenting with hyperleukocytosis

A

Myelomonocytic, acute monocytic, the microgranular variant of APL, and AML with inv16, 11q23 rearrangements, or FLT3-ITD

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62
Q

The circulations most sensitive to the effects of leukostasis

A

CNS, lungs, and penis

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63
Q

Approximately 10% of patients with AML present with a syndrome that includes pancytopenia, often with inapparent blood blast cells, and absence of hepatic, splenic, or lymph nodal enlargement

A

Hypoplastic Leukemia

Approximately 75% of these patients are men older than 50 years.

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64
Q

Two most common symptoms or signs of marrow necrosis

A

Bone pain (approximately 80% of patients)

Fever (approximately 70% of patients)

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65
Q

Marrow findings in marrow necrosis

A

The marrow aspirate is often watery and serosanguineous.

An amorphous extracellular eosinophilic background with disintegrating cells that have lost their staining characteristics with indistinct margins and varying degrees of pyknosis and karyorrhexis

Both technetium scanning and MRI can point to areas of intact marrow that may be used to make a diagnosis of the underlying disease, if it is unknown.

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66
Q

Four myeloproliferative syndromes related to AML have been identified in the neonate:

A

Transient myeloproliferative disorder
Transient leukemia
Congenital leukemia
Neonatal leukemia

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67
Q

Can be present at birth, or occur shortly thereafter, in approximately 10% of infants with Down syndrome.

The blast cells usually have the immunophenotype of megakaryocytes.

A

Transient myeloproliferative disease (TMD)

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68
Q

In Transient myeloproliferative disease (TMD), the elevated white cell and blast cell counts disappear in most patients (approximately 80%) over a period of _____________

A

Weeks to months

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69
Q

Approximately _______of newborns with Down syndrome and transient leukemia develop______________________ in the first __________years of life.

A

25%

Acute megakaryocytic leukemia

First 4 years of life

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70
Q

Mutations that have been found in nearly all patients with TMD and in acute megakaryocytic leukemia in Down patients

A

GATA1 mutations

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71
Q

TMD

Treatment suggested for those patients with severe hepatic fibrosis, very high white cell counts, or hydrops fetalis

A

Very-low-dose cytarabine

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72
Q
A
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73
Q

TMD

Children with Down syndrome have either a ______-fold risk of AML or an approximately ________-fold of ALL by age 5 years

A

150 (AML)

40 (ALL)

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74
Q

Myelogenous leukemia in patients with Down syndrome often has what phenotype of leukemia

A

Megakaryoblastic or erythroid phenotype

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75
Q

Cases of biphenotypic leukemia that are morphologically or cytochemically indicative of myelogenous leukemia

A

LY+AML

The WHO now classifies some of these disorders as mixed phenotype acute leukemia (MPAL).

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76
Q

Cases of biphenotypic leukemia that are more indicative of lymphocytic leukemia

A

MY+ALL

The WHO now classifies some of these disorders as mixed phenotype acute leukemia (MPAL).

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77
Q

2 notable syndromes are associated with hybrid leukemias:

A

(a) the myeloid leukemia and natural killer cell hybrid (CD56+, CD7+, CD13+, CD33+)

(b) the lymphoma, eosinophilia, and t(8;13) myeloid leukemia hybrid.

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78
Q

Often simulates APL, with hypergranular cytoplasm present but an abnormality of chromosome 17 is absent

A

Myeloid–natural killer cell leukemia

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79
Q

Lymphoid and myeloid cells are present simultaneously but are derived from separate clones, or sequential myeloid and lymphoid leukemia are present, but the 2 lineages are derived from separate clones

A

Mixed Leukemias

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80
Q

An unusual but significant concordance has been reported between nonseminomatous mediastinal germ cell tumors and AML, especially the _________________ variant.

A

Megakaryoblastic

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81
Q

Most common in adults, and most frequent variety in infants.

Three morphologic– cytochemical types (M0, M1, M2).

A

Acute myeloblastic leukemia

The WHO has divided acute myeloblastic leukemia not otherwise specified, into 3 types: AML without differentiation, AML without maturation, and AML with maturation.

FAB type M2 or WHO designation AML with maturation

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82
Q

Approximately 15% of patients with AML

More likely to have extramedullary infiltrates in gingiva, skin, or CNS than are patients with acute myeloblastic leukemia

A

Acute Myelomonocytic Leukemia

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83
Q

FAB Classification of Acute Myelomonocytic Leukemia

Variant of myelomonocytic leukemia has increased numbers of marrow eosinophils (10–50%), Auer rods in blast cells, and inversion or rearrangement of chromosome 16

Has an increased risk of CNS involvement, it carries a more favorable prognosis

A

M4Eo

84
Q

Translocations involving ______________ are associated with Acute Myelomonocytic Leukemia

A

Chromosome 3

85
Q

Erythroid leukemia is arbitrarily divided into 3 degrees of severity:

A

(a) Erythroleukemia in which more than 50% of the marrow cells are dysmorphic

(b) Erythroblasts admixed with myeloblasts, the latter composing approximately 20% of nonerythroid cells or approximately 5% to 10% of total marrow cells

(c) Pure erythroid leukemia, in which more than 80% of marrow cells are dysmorphic erythroblasts with a trivial granulocytic proportion of cells and very few if any myeloblasts

86
Q

Features of erythroblasts in Acute Erythroid leukemia

A

Glycophorin A, spectrin, carbonic anhydrase I, ABH blood group antigens, and other antigens that occur on early erythroid progenitors, such as the transferrin receptor (CD71)

Antihemoglobin antibody and antihuman erythroleukemic cell line antibody often are positive

87
Q

TRUE OR FALSE

The more predominant the erythroid component and the lower the proportion of myeloblasts, the better the response to therapy.

A

TRUE

The more predominant the erythroid component and the lower the proportion of myeloblasts, the better the response to therapy.

88
Q

APL occurs with greater frequency among (nationality)

A

Latinos from Europe and South and Central America

89
Q

APL is also increased among persons with an (increased or decreased) body mass index.

A

Increased

Upregulation of polyunsaturated fatty acid metabolism genes has been noted, and in APL patients with obesity, FLT3 mutations are higher.

90
Q

Promyelocytes with multiple Auer rods have been referred to as

A

Faggot cells

91
Q

Leukemic promyelocytes stain intensely with myeloperoxidase and Sudan black and express

A

CD9, CD13, and CD33

BUT NOT CD34 or HLA-DR

92
Q

Microgranular cases represent approximately _____ of patients with promyelocytic leukemia.

The leukemic cells may mimic promonocytes with convoluted or lobulated nuclei.

A

20%

The total WBC often is highly elevated, and severe coagulopathy is prominent in microgranular cases.

93
Q

The most frequent cytogenetic abnormality (>95%) in APL

A

t(15;17)(q22;q21)

94
Q

Other variant translocations in APL

A

Chromosome 3, 5, or 11 and chromosome 17 or isochromosome 17

95
Q

Rearrangement of the RARα gene that is retinoid responsive

A

t(15;17), PML–RARα fusion
t(5:17), NPM–RARα fusion
t(3;17), TBLR1–RARα fusion

96
Q

Rearrangement of the RARα gene that is retinoid resistant

A

t(11;17), PLZF–RARα fusion

97
Q

Mutation in APL where Auer rods are absent and CD56 expression usually is present

A

t(11;17)

98
Q

The PML–RARα gene has 2 isoforms that produce a short-type and a long-type fusion mRNA, respectively.

Patients with the__________ isoform may have a worse outcome

A

Short

FLT3 mutations are frequently found in human disease, especially in the hypogranular variant.

99
Q

APL

Approximately 5% to 10% of patients die during remission induction, most of

A

Hemorrhage
often into the brain

100
Q

Have a higher prevalence (50%) of extramedullary tumors

Hepatomegaly, splenomegaly, and lymphadenopathy are more frequent

A

Acute Monocytic Leukemia

101
Q

In Acute Monocytic Leukemia, monocytic cells react for nonspecific esterase stains, α-naphthyl acetate esterase, and naphthol AS-D-chloroacetate-esterase; in a cytochemical or chemoluminescence assay; or with monoclonal antibodies against monocyte surface antigens, especially ____

A

CD14

Immunoreactivity of cells for lysozyme is characteristic.

102
Q

Results in the MOZ-CBP fusion gene, is characterized by mildly granular promonocytes (simulating hypogranular promyelocytes), intense phagocytosis of red cells, erythroblasts, and sometimes neutrophils and platelets in blood and marrow, simulating macrophagic hemophagocytic syndrome, intravascular coagulation or primary fibrinolysis, and a high frequency of extramedullary disease

A

Acute monoblastic leukemia with t(8;16)

103
Q

TRUE OR FALSE

In acute monocytic leukemia, , examination of cerebrospinal fluid is often recommended, even in the absence of symptoms, when remission has been achieved

A

TRUE

In acute monocytic leukemia, , examination of cerebrospinal fluid is often recommended, even in the absence of symptoms, when remission has been achieved

Greater incidence of CNS or meningeal disease

104
Q

AML prevalent variant of AML that develops in patients with Down syndrome or in patients with mediastinal germ cell tumors and coincident AML

Has severe myelofibrosis

Maturing megakaryocytes with agranular cytoplasm with cytoplasmic protrusions, clusters of platelet-like structures, or shedding of cytoplasmic blebs

A

Acute Megakaryoblastic (Megakaryocytic) Leukemia

105
Q

Markers of Acute Megakaryoblastic (Megakaryocytic) Leukemia

A

Antibodies to von Willebrand factor or to platelet glycoprotein Ib (CD42), IIb/IIIa (CD41), or IIIa (CD61)

106
Q

The eosinophilic cells are dysmorphic and the cytoplasm hypogranulated with smaller-than-normal eosinophilic granules.

A

Acute Eosinophilic Leukemia

Increased eosinophils in the marrow, but not in the blood, is a variant of acute myelomonocytic leukemia and inversion 16 or other abnormalities of chromosome 16, but is not considered an acute eosinophilic leukemia.

107
Q

Acute eosinophilic leukemia

A specific histochemical reaction, _______________________, permits identification of leukemic cells with eosinophilic differentiation and diagnosis of acute eosinoblastic leukemia in some cases of AML with fewer identifiable eosinophils in blood or marrow.

A

Cyanide-resistant peroxidase

108
Q

Proposed as a means of distinguishing acute eosinophilic leukemia from a polyclonal, reactive eosinophilia

A

Overexpression of WT gene expression

109
Q

TRUE OR FALSE

Patients with acute eosinophilic leukemia do not usually develop bronchospastic signs, neurologic signs, and heart failure from endomyocardial fibrosis as is seen in chronic eosinophilic leukemia

A

TRUE

Patients with acute eosinophilic leukemia do not usually develop bronchospastic signs, neurologic signs, and heart failure from endomyocardial fibrosis as is seen in chronic eosinophilic leukemia

Probably because those tissue changes are the result of release of toxins in the granule crystalloid, absent in most eosinophils in acute eosinophilic leukemia and because of the shorter duration of survival in acute eosinophilic leukemia.

110
Q

Appropriate choice for treatment for Acute eosinophilic leukemia

A

Cytarabine and an anthracycline

111
Q

Most cases evolve from the chronic phase of CML

Characterized by presence of CD9, CD25, or both

Elevated blood and urine histamine and urinary methylhistamine levels

A

Acute basophilic leukemia

In some cases of acute myelomonocytic leukemia associated with t(6;9)(p23;q34), basophils may be increased in the marrow, but not in the blood.

112
Q

Acute basophilic leukemia

The cells stain with ____________ and the basophilic granules can be most striking in myelocytes.

A

Toluidine blue or Astra blue

113
Q

Related to a mutation of the KIT gene

Plasma tryptase is elevated

Naphthol AS-D-chloracetate-esterase–positive, CD11b-negative, CD117-positive, CD123-negative

A

Mast cell leukemia

114
Q

The key laboratory distinctions between acute basophilic leukemia and acute mast cell leukemia

A

Basophilic leukemia: naphthol AS-Dchloracetate- esterase–negative, CD11b positive, CD117 negative or weakly positive, CD123 positive, have no increase in cell or plasma tryptase

Mast cell leukemia: naphthol AS-D-chloracetate-esterase–positive, CD11b-negative, CD117-positive, CD123-negative, have an increase in cell and plasma tryptase

115
Q

Defined as elimination of the leukemic cell population in marrow as judged by microscopy and flow cytometry and the restitution of marrow hematopoiesis resulting in a normal or virtually normal white cell, hemoglobin, and platelet concentrations in the blood

A

Remission

116
Q

Any suspicion of APL, however, should lead to urgent administration of ________________

A

ATRA

117
Q

TRUE OR FALSE

Age is a contraindication to treatment, and septuagenarians and octogenarians who are fit cannot enter remissions.

A

FALSE

Age per se is not a contraindication to treatment, and septuagenarians and octogenarians who are fit can enter remissions.

118
Q

More extensive evaluation of coagulation factors should be made if:

A

(a) clotting times are abnormal

(b) bleeding is exaggerated for the level of the platelet count

(c) APL or acute monocytic leukemia is the phenotype

119
Q

Therapy for hyperuricemia is required if:

A

(a) the pretreatment uric acid level is greater than 7 mg/dL (0.4 mmol/L)
(b) the marrow is packed with blast cells, or
(c) the blood blast cell count is moderately or markedly elevated

120
Q

Dose of Allopurinol

A

Allopurinol 300 mg/day

121
Q

Allopurinol can cause allergic dermatitis and should not be used if the uric acid level is less than_________ and the total white cell count is less than approximately _______, as long as hydration is adequate and urine flow is high (>_______ mL/h)

Thus, allopurinol should be discontinued after the risk of acute hyperuricosuria or tumor lysis has passed (usually 4 to 7 days).

A

less than 7 mg/dL

total white cell count is less than approximately 20 × 109/L

> 150 mL/h

122
Q

Reduce plasma urate levels by approximately 80% within 4 hours of the first drug dose.

Recommended dose is 0.2 mg/kg daily for 5–7 days IV

A

Recombinant urate oxidase (rasburicase)

123
Q

The primary goal of induction therapy in AML

A

Complete remission
* <2% blasts in the marrow)
* A neutrophil count greater than 1 × 109/L
* Platelet count greater than 100 × 109/L

124
Q

Current standard induction treatment for non-APL AML

A

Anthracycline or Anthraquinone and Cytarabine

125
Q

The two most important variables in remission-induction therapy

A

Age of the patients
Proportion of patients with therapy-induced leukemia or an antecedent clonal myeloid disease (clonal evolution)

126
Q

Anthracycline that does not induce P-glycoprotein expression -> drug resistance is reduced

A

Idarubicin

127
Q

May be given during induction to reduce the risk of cardiotoxicity in patients at higher-than-usual risk because of a history of coronary artery disease or congestive heart failure

A

Dexrazoxane

128
Q

TRUE OR FALSE

High-dose cytarabine does not increase complete remission rates and increases toxicity compared to conventional doses, especially in patients over 60 years of age

A

TRUE

High-dose cytarabine does not increase complete remission rates and increases toxicity compared to conventional doses, especially in patients over 60 years of age

129
Q

The effect of induction chemotherapy is usually assessed by marrow aspirate and biopsy _______days after completion of chemotherapy.

A

7–10 days

“day 14 marrow”

Hypocellular marrow and no evidence of residual leukemic blasts: recovery of normal counts is awaited

Hypocellular marrow and a small number of residual blasts: additional therapy may be delayed until count recovery or until another marrow assessment often recommended at a 1 week interval after the “day 14 marrow” examination.

Sgnificant amounts of leukemic cells remaining: repeating the original induction therapy or use of a high-dose cytarabine regimen

130
Q

REINDUCTION CHEMOTHERAPY

TRUE OR FALSE

There are insufficient data to determine whether use of the same regimen or advancing to a high-dose cytarabine-containing regimen is the superior approach.

A

TRUE

There are insufficient data to determine whether use of the same regimen or advancing to a high-dose cytarabine-containing regimen is the superior approach.

131
Q

Approximately ____ of patients with persistent AML after 1 course of induction therapy have a complete remission after a second course, and disease-free survival at 5 years is approximately ___

A

40%

10%

132
Q

A multitargeted kinase inhibitor, was approved by the FDA in 2017 for use in AML patients with FLT3 ITD or TKD point mutations

A

Midostaurin (ITD or TKD)

Sorafenib (ITD)

133
Q

Second-generation FLT3 inhibitor

A

Gilteritinib and crenolanib

134
Q

A humanized anti-CD33 monoclonal antibody conjugated to calicheamicin that has now been approved for addition to 7+3 chemotherapy

A

Gemtuzumab ozogamicin (GO)

3 mg/m2 on days 1, 4, and 7

135
Q

The main toxicity of Gemtuzumab ozogamicin (GO)

A

Prolonged thrombocytopenia

136
Q

A liposomal preparation of daunorubicin hydrochloride and cytarabine liposome in a fixed 1:5 molar ratio, was approved for use by the FDA in 2017 for patients over 60 years with AML and in those with secondary AML or MDS-related cytologic findings

A

CPX-351

137
Q

Use has been primarily in patients over 60 years deemed unfit for standard induction chemotherapy

A

Hypomethylating Agents

Decitabine
5-Azacytidine

138
Q

Oral bioavailable small molecule inhibitor of BCL-2

Demonstrated synergistic activity with hypomethylating agents

Approved in the United States for use in previously untreated AML patients older than 75 years in combination with low-intensity chemotherapy,

A

Venetoclax

139
Q

A hedgehog pathway inhibitor approved by the FDA in 2018 for oral administration in combination with low-dose cytarabine for newly diagnosed AML patients 75 years old and older or who have comorbidities that preclude use of intensive induction chemotherapy

A

Glasdegib

140
Q

Toxicity of Glasdegib

A

Muscle cramps, dysgeusia, and prolonged QT interval

141
Q

Oral inhibitor of IDH2:
Oral inhibitor of IDH1:

A

Oral inhibitor of IDH2: Enasidenib
Oral inhibitor of IDH1: Ivosidenib

**Only ivosidenib has been approved for initial therapy

142
Q

Side effects of hypomethylating agents

A

Constipation

143
Q

Side effect of Ivosidenib

A

Differentiation syndrome

144
Q

Most serious complications of hyperleukocytosis:

A

Intracranial hemorrhage or pulmonary insufficiency

145
Q

In management of hyperleukocytosis: - Hydration should be administered promptly to maintain urine flow greater than ____________

A

100 mL/h per m2

146
Q

Hydroxyurea dose for Cytoreduction

A

Hydroxyurea 1.5–2.5 g orally every 6 hours (total dose 6–10 g/day) for approximately 36 hours

Appropriate remission-induction therapy should be initiated as soon as possible after the leukocyte count has been decreased significantly.

147
Q

Simultaneous_____________________ can decrease blast cell concentration by approximately _______ within several hours without contributing to uric acid or cellular phosphate release.

A

Leukapheresis

30%

148
Q

____________________ may improve the hypoxemia related to hyperleukocytosis

A

Inhaled nitric oxide

149
Q

TRUE OR FALSE

Patients with evidence of intravascular coagulation or exaggerated primary fibrinolysis should be considered for platelet and fresh-frozen plasma administration before antileukemic therapy is started.

A

TRUE

Patients with evidence of intravascular coagulation or exaggerated primary fibrinolysis should be considered for platelet and fresh-frozen plasma administration before antileukemic therapy is started.

150
Q

Infusion of cryoprecipitate can be used for fibrinogen levels less than approximately ____________

A

125 mg/dL

151
Q

Intravascular coagulation or primary fibrinolysis may occur in patients with _____________

A

APL and acute monocytic leukemia

152
Q

Management of CNS disease

Prophylactic therapy usually is not indicated, but examination of the spinal fluid after remission should be considered in:

A

(a) monocytic subtypes;
(b) cases with extramedullary disease;
(c) cases with inversion 16 and t(8;21) cytogenetics;
(d) CD7+ and CD56+ (neural cell adhesion molecule) immunophenotypes; and
(e) patients who present with very high blood blast cell counts

153
Q

TRUE OR FALSE

Prophylactic intrathecal chemotherapy is recommended if low-dose cytarabine is used for consolidation.

A

FALSE

Prophylactic intrathecal chemotherapy is NOT recommended if high-dose cytarabine is used for consolidation.

154
Q

Treatment of meningeal leukemia

A

High-dose IV cytarabine (which penetrates the blood–brain barrier)
Intrathecal methotrexate
Intrathecal cytarabine
Cranial radiation
Chemotherapy and radiation in combination

155
Q

If CNS leukemia is present, intrathecal therapy is often given:

A

Twice per week until blasts are cleared, and then once per week for 4–6 weeks

This therapy can be accomplished via the lumbar puncture route or through placement of an Ommaya reservoir.

156
Q

If there is a mass present treatment can be:

A

Radiation or high-dose cytarabine with glucocorticoids

157
Q

TRUE OR FALSE

Unless the patient has neurologic symptoms, lumbar puncture generally is deferred until blood blast cells have cleared.

A

TRUE

Unless the patient has neurologic symptoms, lumbar puncture generally is deferred until blood blast cells have cleared.

No consensus exists on a trigger for platelet transfusion in adults with AML undergoing lumbar puncture; a platelet count of less than 20 × 109/L has been proposed as such a trigger, but many therapists use a higher platelet count (eg, 50 × 109/L) as a safety threshold for lumbar puncture.

158
Q

Myeloid sarcoma may be the presenting finding in approximately ____ of patients with AML.

A

1%

Patients with trisomy 8 have poorer survival rates.

159
Q

Treatment for Nonleukemic Myeloid Sarcoma

A

Intensive AML induction therapy

160
Q

Post remission therapy for patients with good risk cytogenetics and can also be considered in those with intermediate-risk cytogenetics

A

4 cycles of high-dose cytarabine

161
Q

Post remission therapy for patients with poor-risk cytogenetics

A

Allogeneic HSC transplantation

162
Q

Associated with benefit from high-dose cytarabine therapy:

A cycle is typically 3 g/m2 twice daily on days 1, 3, and 5, providing 6 doses per cycle

A

RAS mutations
CBF leukemias, such as t(8;21)
Patients 60 years or younger, if they have adequate renal function
NPM1 mutation without FLT3-ITD mutation
Biallelic CEBPα mutations

163
Q

High-dose cytarabine frequently causes conjunctivitis and photophobia hence this should be given

A

Glucocorticoid eyedrops are usually used every 6 hours for 24–72 hours after the last dose of the drug

164
Q

May decrease the likelihood of severe cerebellar toxicity associated with Cytarabine

A

1-hour duration infusion of high-dose or reduced-dose (eg, 2 g/m2) cytarabine

Patients over age 60 years and patients with renal insufficiency require dose attenuation (ie, to 1–2 g/m2).

165
Q

Autologous marrow or blood stem cell rescue can be used in patients with

A

AML who achieve a remission, do not have a compatible stem cell donor, and are into the eighth decade of life

166
Q

An adoptive immunotherapy with donor mononuclear cell infusions is sometimes used to treat relapse of leukemia after allografting

A

Donor Leukocyte Infusion

Most effective in early relapses and in the absence of extensive of chronic GVHD.

167
Q

The major complications of Donor Leukocyte Infusion

A

GVHD and marrow aplasia

168
Q

It can be used alone or with hypomethylating agents as treatment for posttransplantation relapse.

A

Sorafenib

169
Q

After patients complete consolidation therapy, they are generally followed with blood counts every _______________

A

Rvery 3 months for 2 years, and then every 3–6 months for 5 years.

170
Q

A predictive factor for relapse

A

Time taken to enter complete remission after induction

171
Q

TRUE OR FALSE

In patients who relapse more than 1 year after the first remission, the original remission-induction regimen can be readministered or a combination salvage chemotherapy regimen can be administered.

A

TRUE

In patients who relapse more than 1 year after the first remission, the original remission-induction regimen can be readministered or a combination salvage chemotherapy regimen can be administered.

172
Q

Defined as leukemia that does not respond to 2 initial induction chemotherapy treatments with cytarabine and an anthracycline or anthraquinone.

A

Refractory leukemia

173
Q

Leukemia that reoccurs following a remission

A

Relapsed leukemia

174
Q

Second-generation DNA methylation inhibitors

A

Guadecitabine

175
Q

Can promote histone acetylation and gene transcription in RUNX1/ETO-positive leukemic cells

A

Depsipeptide

176
Q

An aminonucleoside inhibitor of DOT1L histone methyltransferase activity is under clinical investigation in MLL-rearranged leukemias.

A

Pinometostat

177
Q

Are small molecule inhibitors of MDM2 (Murine Double Minute 2)

A

Nutlins / Idasanutlin

178
Q

An oral exportin-1 inhibitor

A

Selinexor

179
Q

A CDK6 inhibitor has activity in MLL-rearranged leukemias

A

Palbociclib

180
Q

A CDK9 inhibitor, is being examined as an MCL-1 inhibitor

A

Alvocidib

181
Q

Inhibitor of oxidative phosphorylation

A

Metformin
Mubritinib

182
Q

An oral iron chelator, inhibits leukemic CD34+CD38− cells through NF-κB inhibition and reactive oxygen species generation

A

Deferasirox (Exjade)

183
Q

TRUE OR FALSE

Patients who are suspected based on morphology and presence of coagulopathy should begin ATRA without waiting for definitive FISH or molecular confirmation.

A

TRUE

Patients who are suspected based on morphology and presence of coagulopathy should begin ATRA without waiting for definitive FISH or molecular confirmation.

184
Q

In APL, those with WBC of ________________ or higher are considered to have high-risk disease

A

10 × 109/L

185
Q

Used alone, ATRA can induce a short-term remission in at least _______ of patients.

A

80%

186
Q

Leukocytosis during ATRA–arsenic trioxide therapy in patients with white cell counts higher than 10 × 109/L can be treated with _____________.

A

Hydroxyurea or idarubicin

187
Q

Chemotherapy for APL

Low-risk disease:

High-risk patients:

A

Chemotherapy for APL

Low-risk disease: A combination of ATRA plus arsenic trioxide, ATRA plus idarubicin alone, or ATRA plus daunorubicin plus cytarabine
High-risk patients: ATRA plus daunorubicin and cytarabine, ATRA plus idarubicin, or ATRA and arsenic trioxide with idarubicin (dose-adjusted based on age)

188
Q

Variant of APL, in which the promyelocytic leukemia zinc finger (PLZF) gene is fused to RARα, DOES NOT respond to ATRA.

A

t(11;17)

189
Q

With ATRA, leukemic promyelocytes disappear from the blood in ______weeks, and a normal marrow aspirate maybe obtained in ______ weeks.

A

2–4 weeks

4–10 weeks

190
Q

A rapid increase in the total blood leukocyte count to as high as 80 × 109/L in the first several weeks of therapy of APL

A

Differentiation syndrome

(previously called the retinoic acid syndrome)

191
Q

Treatment of differentiation syndrome

A

Early use of cytotoxic chemotherapy and glucocorticoid administration

Dexamethasone 10 mg IV every 12 hours

192
Q

TRUE OR FALSE

Arsenic trioxide can trigger apoptosis of APL cells at low concentrations and maturation at high concentrations.

A

FALSE

Arsenic trioxide can trigger apoptosis of APL cells at high concentrations and maturation at low concentrations.

193
Q

TRUE OR FALSE

In those patients treated with ATRA plus arsenic trioxide, and white cell count lower than 10 × 109/L at diagnosis, no maintenance is required.

A

TRUE

In those patients treated with ATRA plus arsenic trioxide, and white cell count lower than 10 × 109/L at diagnosis, no maintenance is required.

194
Q

APL maintenance is usually recommended for ______ years.

A

2 years.

195
Q

Exposure to wha drugs can lead to AML with MLL gene rearrangements on chromosome 11q32.

A

Topoisomerase II inhibitors (eg, etoposide, mitoxantrone, amsacrine)

196
Q

Latency period for development of AML after:

Topoisomerase II Inhibitors :
Alkylating Agents and Cisplatin :

A

Topoisomerase II Inhibitors : 2 years
Alkylating Agents and Cisplatin : 6 years

197
Q

The most common cytogenetic changes in secondary AML from Alkylating Agents and Cisplatin

A

Deletions of all or part of chromosome 5 or 7

198
Q

Other drugs that may increase the risk of secondary leukemias:

A

Low-dose weekly methotrexate for rheumatoid arthritis
Etanercept therapy
Temozolamide
Growth hormone administration
G-CSF given to patients with congenital, but not idiopathic or cyclic neutropenia.

199
Q

Leukemia (AML, ALL, CML) is the _________ most common malignancy of women in the childbearing age group

A

Second

200
Q

AML in Pregnancy

If the pregnancy is not terminated,_______________ might be useful in the__________________ trimester, when chemotherapy poses a high risk to the embryo.

A

Leukapheresis

First

201
Q

The preferred anthracycline to treat pregnant women as it has lower transplacental transfer

A

Doxorubicin

202
Q

TRUE OR FALSE

Leukemic infiltrates can be found on both the maternal side of the placenta and the villi.

A

FALSE

Leukemic infiltrates can be found on the maternal side of the placenta, but usually not in the villi.

203
Q

Management of Neutropenic Enterocolitis

A

Bowel rest, nasogastric suction, fluids, and antibiotics

**Parenteral alimentation is sometimes used but is generally not helpful.

** Right hemicolectomy is usually done only if hemodynamic stability is lost

204
Q

Definition of Remission

A

Neutrophil count greater than 1 × 109/L
Platelet count greater than 100 × 109/L
Less than 5% blasts in the marrow by microscopy
Absence of extramedullary AML

205
Q

Early death can occur during induction chemotherapy, and ____________and ___________are the most important predictors of treatment-related mortality.

A

Performance status and age

206
Q

The two most compelling determinants of a poor outcome in AML

A

Older age and less-favorable cytogenetic risk

WILLIAM'S HEMATOLOGY (89 decks)

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