Hematologic Malignancies

Question 1

What is the single most common childhood malignancy?

Answer 1

ALL

Question 2

What are the three main types of leukemia in children?

Answer 2

Acute lymphoblastic leukemia, Acute myeloid leukemia, and Chronic myeloid leukemia

Question 3

***Image 24-21, differentiate between myeloblast and lymphoblast

Answer 3

***Image 24-21

Question 4

From what cell type does acute lymphoblastic leukemia arise?

Answer 4

Lymphoid precursor cells

Question 5

From what cell type does acute myeloid leukemia arise?

Answer 5

Myeloid precursor cells

Question 6

From what cell type does chronic myeloid leukemia arise?

Answer 6

WBC stem cells

Question 7

Which (7) disorders correlate with increased risk of ALL?

Answer 7

Prenatal radiation exposure, postnatal exposure to high doses of radiation, Trisomy 21, Ataxia-telangiectasia, Bloom syndrome, Fanconi Anemia, and neurofibromatosis.

Question 8

What diagnosis should you consider in a child with pallor and a limp?

Answer 8

ALL

Question 9

What are the “four Ps” of ALL?

Answer 9

They describe the most common presentation of ALL: Pallor, Pyrexia, Purpura, and Pain.

Question 10

T/F: Splenomegaly is common in ALL.

Answer 10

True. In addition to fever, bleeding, and bone pain, lymphadenopathy is typical. Generalized lymphadenopathy and hepatosplenomegaly are seen in > 50% of patients.

Question 11

Which (4) cytopenias are often seen in children with ALL?

Answer 11

Normocytic normochromic anemia, reticulocytopenia, severe neutropenia (despite high WBC count), and thrombocytopenia.

Question 12

What test is required to diagnose ALL? What must it show in order to be diagnostic?

Answer 12

Bone marrow evaluation is required for diagnosis and must show at least 25% marrow involvement to be diagnostic.

Question 13

What is the classic bone marrow finding in patients with ALL?

Answer 13

The marrow is classically hypercellular and infiltrated with leukemic lymphoblasts. ***Image 24-22

Question 14

List 5 good prognostic indicators for ALL.

Answer 14

Rapid response to treatment, hyperdiploidy (> 50 chromosomes or DNA index > 1.16), Trisomies of chromosomes 4 and 10, t(12;21) translocation (TEL-AML), and female gender.

Question 15

List 7 poor prognostic indicators for ALL.

Answer 15

Age < 1 year or > 10 years at diagnosis, presence of the Philadelphia chromosome t(9;22), abnormalities of the MLL gene (i.e. t(4;11)), WBC count > 50,000 cells/µL on presentation, mature B-cell leukemia, T-cell leukemia, and African American or Hispanic ethnicity.

Question 16

What are the four general treatment regimen categories for ALL?

Answer 16

Induction, consolidation, maintenance, and CNS preventive therapy.

Question 17

Which four drugs/drug categories are used in the induction phase of ALL treatment?

Answer 17

Vincristine, glucocorticoid (dexamethasone or prednisone), asparaginase, and anthracyclines (doxorubicin or daunorubicin - for patients who are higher risk at time of diagnosis).

Question 18

How common is remission in patients with standard-risk ALL following the induction phase of their treatment regimen?

Answer 18

More than 95% of patients with standard-risk ALL enter remission following induction therapy.

Question 19

Which patients with ALL receive CNS preventive therapy?

Answer 19

Every patient with ALL receives CNS preventive therapy, regardless of the initial CNS findings.

Question 20

What is the typical length of the treatment course in patients with ALL?

Answer 20

Most patients receive 30-36 months of therapy.

Question 21

How long does the induction phase of treatment typically last in patients with ALL?

Answer 21

About a month.

Question 22

How long does the consolidation phase of treatment typically last in patients with ALL?

Answer 22

About 6-12 months.

Question 23

Which (5) drugs are typically used in the consolidation phase of ALL treatment? What is the goal of treatment in this phase?

Answer 23

The goal of treatment is to intensify therapy by introducing different drugs and combinations that have synergistic effects to reduce the chance for drug resistance. Cytarabine, anthracyclines, methotrexate, cyclophosphamide, and etoposide are most commonly used.

Question 24

How long does the maintenance phase of ALL treatment typically last?

Answer 24

18-24 months

Question 25

What (4) drugs are typically used in the maintenance phase of treatment for ALL?

Answer 25

Most treatment protocols use daily oral 6-mercaptopurine (6-MP) and weekly methotrexate with intermittent pulses of vincristine and glucocorticoids.

Question 26

What is the most important predictive factor for achieving a 2nd remission in ALL?

Answer 26

The length of time the first remission lasted (i.e. the longer the first remission, the better the survival rate).

Question 27

Which two agents commonly used in the treatment of ALL have hepatotoxicity as a long-term side effect?

Answer 27

Hepatotoxicity occurs with antimetabolite therapy (methotrexate and 6-MP).

Question 28

Which two agents commonly used in the treatment of ALL have cardiomyopathy as a long-term side effect?

Answer 28

Cardiomyopathy is seen with the anthracyclines (doxorubacin and daunorubacin.

Question 29

What secondary malignancy is a known long-term side effect of etoposide use?

Answer 29

Acute myeloid leukemia

Question 30

What (9) disorders/exposures correlate with an increased risk of AML?

Answer 30

Trisomy 21, Diamond-Blackfan anemia, Fanconi anemia, Bloom syndrome, Kostmann syndrome, Paroxysmal nocturnal hemoglobinuria, neurofibromatosis, and previous exposure to Etoposide or ionizing radiation.

Question 31

What is leukemia cutis?

Answer 31

Leukemic infiltration of the skin, which can be seen in the M4/M5 subtypes of AML.

Question 32

What is an orbital chloroma, and what might its presence signify?

Answer 32

Chloromas are localized masses of leukemic cells and are often present at the time of AML diagnosis (or could be the 1st clue to diagnosis).

Question 33

What procedure is required for the diagnosis of AML?

Answer 33

Bone marrow evaluation.

Question 34

What peripheral blood cell finding is pathognomonic for AML?

Answer 34

Finding Auer rods inside peripheral blast cells in the blood is pathognomonic for AML. ***Image 24-24

Question 35

Know how to identify an Auer rod associated with AML (image 24-24). ***

Answer 35

***

Question 36

Which karyotype is associated with Acute Promyelocytic Leukemia?

Answer 36

t(15;17)

Question 37

What disorder is commonly present in patients presenting with new-onset Acute Promyelocytic Leukemia?

Answer 37

DIC

Question 38

Which three drug classes are typically used in the induction phase of AML treatment?

Answer 38

Anthracyclines, etoposide, and cytosine arabinoside (Ara-C).

Question 39

Which subset of AML patients tend to have excellent cure rates?

Answer 39

Patients with Acute Promyelocytic Leukemia. They receive retinoic acid in addition to chemotherapy and do not require bone marrow transplant.

Question 40

Which leukemia is commonly associated with the Philadelphia chromosome?

Answer 40

Philadelphia chromosome-positive CML.

Question 41

What is the Philadelphia chromosome?

Answer 41

t(9;22) chromosome translocation, which is associated with CML.

Question 42

What is the typical management for Philadelphia chromosome-positive CML if diagnosed in the chronic phase of disease?

Answer 42

Most patients are treated initially with tyrosine kinase inhibitors such as imatinib or dasatinib. These drugs can induce complete remission with a favorable side-effect profile, but must be taken for life as they are not curative.

Question 43

Patients with which disorder have an increased risk for the development of juvenile myelomonocytic leukemia (JMML)?

Answer 43

Neurofibromatosis Type 1

Question 44

Does JMML usually present with a small or enlarged spleen?

Answer 44

Children present with a markedly enlarged spleen, modest leukocytosis, thrombocytopenia, and elevated fetal hemoglobin.