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Flashcards in Quiz Questions 5 Deck (16)
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1
Q

Main dose limiting side effect of Vinblastine is:

  • Peripheral Neuropathy
  • Urinary retention
  • Nausea and Vomitting
  • Bone marrow suppression
  • Constipation
A

Bone marrow suppression

This is in contrast to the similar “spindle poison” called vincristine. The dose limiting toxicity associated with vincristine when administered at recommended dose is peripheral and autonomic neuropathies.

  • Peripheral Neuropathy
  • Peripheral neuropathy is not common with this drug. It is more common with a similar drug called vincristine.
  • Urinary retention
  • Urinary retention may be secondary to an autonomic neuropathy induced by vincristine. It is uncommon with vinblastine use.
  • Nausea and Vomitting
  • Gastric distress is not characteristic of vinblastine.
  • Constipation
  • Constipation may be secondary to an autonomic neuropathy induced by vincristine. It is uncommon with vinblastine use.
2
Q

Mechanism of action of anthracyclines is:

  • Generation of semiquinone free radicals and O2 free radicals
  • Inhibition of topoisomerase I
  • Inhibition of microtubules
  • Crosslinking DNA
A

Generation of semiquinone free radicals and O2 free radicals

This class of chemotherapeutics works by the formation of free oxygen radicals. These radicals result in DNA strand breaks and subsequent inhibition of DNA synthesis and function. Anthracyclines also inhibit the enzyme topoisomerase II by forming a complex with the enzyme and DNA. Topoisomerases are a class of enzymes that serve to unwind the DNA double strand helix to allow for DNA repair, replication and transcription. This class of chemotherapeutics is not cell cycle specific. The most important side effect of this group of drugs is cardiac toxicity. The same free radicals that serve to damage the DNA of the cancer cell may damage the cells of the heart muscle. Oncologists monitor heart function very carefully when patients are on these medications.

  • Inhibition of topoisomerase I
  • An example of a topoisomerase I inhibitor is irinotecan.
  • Inhibition of microtubules
  • An example of a microtubule inhibitor is vincristine.
  • Crosslinking DNA
  • Crosslinking of DNA is a characteristic of alkylating agents.
3
Q

Alkylating agents do not increase the risk of secondary malignancies especially acute myeloid leukemia.

True or false

A

false

In general, prolonged use of these drugs will lead decreased sperm production, cessation of menstruation, and possibly cause permanent infertility. This class of chemotherapeutics should never be used in the first trimester of pregnancy as they are been shown to increase fetal malformations. Use in the second or third trimester does not seem to carry the same risk. All alkylating agents can cause secondary cancers although not all agents are equal in their carcinogenic potential. The most common secondary cancer is a leukemia (Acute Myeloid Leukemia) that can occur years after therapy.

4
Q

Regarding the mechanism of action of alkylating agents, which of the following is correct?

  • Inhibition of topoisomerase II
  • Cross-linking of DNA
  • Inhibition of microtubules
  • Inhibition of topoisomerase I
A

Cross-linking of DNA

Alkylating agents are the oldest class of anticancer drugs. Almost all of these drugs are active or latent nitrogen mustards. Nitrogen mustards are various poisonous compounds originally developed for military use. Alkylating agents all share a common mechanism of action but differ in their clinical activity. They attack the negatively charged sites on the DNA – the oxygen, nitrogen, phosphorous and sulfur atoms. By binding to the DNA, replication, transcription and even base pairing are significantly altered. Alkylation of the DNA also leads to DNA strand breaks and DNA strand cross-linking. By altering DNA in this manner, cellular activity is effectively stopped and the cell will die. Chemotherapy drugs in this class are active in every stage of the cell cycle. As a consequence, this class of anticancer drugs is very powerful and is used in most every type of cancer both solid tumors and leukemia. Some of the more common alkylating agents include: Cyclophosphamide, Ifosphamide, Melphalan, Chlorambucil, BCNU, CCNU, Dacarbazine, Procarbazine, Busulfan, and Thiotepa.

  • Inhibition of topoisomerase II
  • Topo II inhibition is not a characteristic of alkylating agents. An example of a topo II inhibitor is daunomycin.
  • Inhibition of microtubules
  • Alkylators do not affect microtubules. An example of a microtubule inhibitor is vinblastine.
  • Inhibition of topoisomerase I
  • Alkylators do not affect topo I. An example of a topo I inhibitor is Topotecan.
5
Q

Vinca alkaloids main cytotoxic effect is in the S-phase of the cell cycle.

True or False

A

false

Vinca alkyloids are often referred to as “spindle poisons” because they inhibit the cell cycle in the M phase.

6
Q

Alemtuzumab is a Anti-CD52 monoclonal antibody. This is used to treat B cell lymphoid malignancies.

True or False

A

false

CD52 antigen is present on both B & T cells. For this reason, the alemtuzumab has activity against both cell lines.

7
Q

Specific genetic abnormalities have important prognostic and therapeutic implications. Fms-like tyrosine kinase 3 (FLT3) and Nucleophosmin (NPM1) exon 12 gene mutations are examples of these genetic abnormalities.

Which of the following combinations is an independent predictor of a unfavorable outcome?

  • NPM1-/FLT3ITD+
  • NPM1+/FLT3ITD-
  • NPM1+/FLT3ITD+
  • NPM1-/FLT3ITD-
A

NPM1+/FLT3ITD-

8
Q

Richters transformation is characterized by

  • Isolated lymph node transforming to aggressive lymphoma
  • When all lymph nodes regress and disease is quiescent
  • Disease systemically flares up with no change in lymph nodes
  • None of the above
A

Isolated lymph node transforming to aggressive lymphoma

In Richter’s syndrome chronic lymphocytic leukemia progresses to a more advanced cell type. Typically a lymph node begins to enlarge and evidence of a more aggressive lymphoma becomes apparent on biopsy or in the peripheral blood.

  • When all lymph nodes regress and disease is quiescent
  • Spontaneous partial remissions of indolent lymphomas can occur; however, this is not a characteristic of Richter’s syndrome.
  • Disease systemically flares up with no change in lymph nodes
  • It would be very unusual for Richter’s syndrome to occur without an accompanying increase in lymph nodes size.
9
Q

Which of the following statements about Chronic Lymphocytic Leukemia (CLL) is INCORRECT

  • Hypogammaglobinemia is a feature of CLL in up to 50% of patients in advanced disease
  • Characteristic markers for CLL is CD 19 and CD 9
  • Patients with mutated forms of Immunoglobulin gene have a more indolent course
  • Deletion of 17p is consistent with poor prognosis.
A

Characteristic markers for CLL is CD 19 and CD 9

A characteristic of B cell CLL is that the malignant lymphocyte surfaces express B cell markers (CD 20, CD 19, CD 23) and CD 5 (an aberrant T cell marker). CD 9 is a surface marker frequently seen in acute nonlymphocytic leukemia or acute lymphoblastic leukemia, but not in CLL.

  • Hypogammaglobinemia is a feature of CLL in up to 50% of patients in advanced disease
  • This answer is true depending upon the duration and stage of the disease.
  • Patients with mutated forms of Immunoglobulin gene have a more indolent course
  • Hypermutation of the immunoglobulin gene of lymphocytes are normal and implies that the lymphocytes are undergoing normal maturation. It is a good prognostic factor. This is in contrast to a lack of hypermutation, often characterized by the presence of ZAP=70 protein and CD38 markers, which are poor prognostic factors.
  • Deletion of 17p is consistent with poor prognosis.
  • Deletion of 17p implies a poor response to chemotherapy.
10
Q

Autoimmune thrombocytopenia can occur with Chronic Lymphocytic Leukemia.

True or false

A

true

Concurrent autoimmune disorders are not uncommon among patients with lymphoproliferative neoplasms including CLL. The presence of either warm autoimmune hemolysis or immune thrombocytopenia can fool the clinician into thinking the patient has more advanced disease than is really present. Never the less, the occurrence of these complications may require more aggressive intervention than normally required according to the stage category.

11
Q

Regarding the clinical findings of Chronic Myelogenous Leukemias, which of the following is correct?

  • Patients present always with vaso-occlusive disease symptoms inc. MI, venous thrombosis, priapism, pulmonary insufficiency
  • Presence of splenomegaly despite continued treatment is a sign of disease acceleration
  • The total WBC is usually low and patients present with circulating blasts > 20%
  • Bone marrow cellularity is increased with an increased erythroid to myeloid ratio
A

Presence of splenomegaly despite continued treatment is a sign of disease acceleration

The thrombotic risk in patients with CML is relatively low when compared to that seen in patients with other myeloproliferative processes (e.g. essential thrombocythemia, polycythemia vera, myelofibrosis) and when it occurs is often after entry into the accelerated phase or after certain kinds of treatment. Most patients with CML present with an elevated WBC, hypercellular bone marrow (and markedly increased M:E ratio) due to the uncontrolled proliferation of the granulocyte precursors. The majority of patients with CML have splenomegaly which almost always reduces in size with an appropriate response to therapy.

12
Q

The following are all indications of treatment except:

  • Progressive Fatigue
  • Asymptomatic lymphadenopathy
  • Rai Stage III or IV disease
A

Rai Stage III or IV disease

The presence of anemia and/ or thrombocytopenia are generally considered to be indications to begin treatment.

  • Progressive Fatigue
  • Progressive fatigue is almost always a sign of worsening disease and requires intervention.
  • Asymptomatic lymphadenopathy
  • Enlarging lymph nodes are not an indication for treatment unless they are causing symptoms.
13
Q

BCR protein binding to ABL results in which of the following functional changes

  • ABL protein becomes constitiutely active to a TK enzyme & in turn prevents apoptosis
  • DNA binding protein activity of ABL is attenuated
  • Binding protein of abl to actin is enhanced
  • All of the above
  • None of the above
A

All of the above

The BCR-ABL fusion protein has multiple activities which may play roles in the pathogenesis of CML. It is assumed at this time that its primary effect is thought to be the constitutive activation of tyrosine kinase which results in the uncontrolled proliferation of granulocyte precursors in the bone marrow.

14
Q

Treatment options for Chronic Lymphocytic Leukemia include Fludarabine, Cyclophosphamide and Rituximab. If a patient has autoimmune hemolytic anemia, fludarabine is the preferred agent of choice in these patients.

True or false

A

false

When administered as a single agent fludarabine can cause a severe, life-threatening hemolysis that is difficult to treat. When administered in conjunction with either cyclophosphamide and/or rituximab the frequency of this complication is reduced significantly. Clinical trials indicate that the response rate and duration of response is improved by the administration of this three drug combination as compared when of these three drugs are administered alone.

15
Q

The following regarding staging of Chronic Lymphocytic Leukemia are all correct EXCEPT:

  • Stage I - Lymphocytosis and lymphadenopathy
  • Stage 0 - Lymphadenopathy
  • Stage 2 – organomegaly
  • Stage III – anemia
  • Stage IV – thrombocytopenia
A

Stage 0 - Lymphadenopathy

In stage 0 chronic lymphocytic leukemia, there are too many lymphocytes in the blood, but there are no other symptoms of leukemia.

  • Stage I - Lymphocytosis and lymphadenopathy
  • In stage I chronic lymphocytic leukemia, there are too many lymphocytes in the blood and the lymph nodes are larger than normal.
  • Stage 2 – organomegaly
  • In stage II chronic lymphocytic leukemia, there are too many lymphocytes in the blood, the liver or spleen is larger than normal, and the lymph nodes may be larger than normal.
  • Stage III – anemia
  • In stage III chronic lymphocytic leukemia, there are too many lymphocytes in the blood and there are too few red blood cells. The lymph nodes, liver, or spleen may be larger than normal.
  • Stage IV – thrombocytopenia
  • In stage IV chronic lymphocytic leukemia, there are too many lymphocytes in the blood and too few platelets. The lymph nodes, liver, or spleen may be larger than normal and there may be too few red blood cells.
16
Q

Chronic Lymphocytic Leukemia is a clonal malignancy involving:

  • B lymphocytes
  • T lymphocytes
  • B and T lymphocytes
A

B lymphocytes

Characteristically CLL is a monoclonal disease of B lymphocytes.

  • T lymphocytes
  • Monoclonal T cell lymphoproliferation is not typical of CLL.
  • B and T lymphocytes
  • Mixed lineage CLL is not typical