The Leukemias, Chronic & Acute

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30; 50

Chronic lymphocytic leukemia (CLL), unusual in persons younger than ____ years, becomes increasingly frequent with age and 85% to 90% of patients are over age ____.

Males

Is CLL more common in males or females?

CLL

These patients are found to have lymphocytosis, enlarged lymph nodes or spleen on routine examination or during evaluation of apparently unrelated diseases.

Fatigue or a sense of lack of well-being

What is the most frequent initial complaint in CLL?

CLL

The initial complaint is enlarged lymph nodes or the development of an infection and less frequently, symptoms related to splenomegaly anemia and/or bleeding.

CLL

As the disease progresses, splenomegaly and hepatomegaly develop. Also, pallor related to anemia and petechiae or ecchymosis related to thrombocytopenia. Infections, most often bacterial pneumonia, is a fairly frequent finding.

5 X 10^9/L; bone marrow; low; CD19 or CD20; CD5

Confirmation of diagnosis of CLL requires: peripheral blood absolute lymphocyte count > ____ for more than four weeks; ____ lymphocytosis > 30%; monoclonal surface immunoglobin (usually IgM Kappa) pattern with ____ staining intensity, positive for at least one B-cell antigen (____ or ____), & simultaneous demonstration of a T-cell marker (____) on B-cell-antigen positive cell population.

Abnormal B-lymphocytes

What is responsible for the immunologic abnormalities found in CLL?

Hypogammaglobulinemia

____ occurs in 50 to 70% of patients with CLL and is a major contributor to the increased risk of infections, particularly with encapsulated organisms.

CLL

Patients with ____ are unable to produce antibodies when stimulated by an antigen.

CLL

Patients in advanced stages of ____ should not receive vaccinations with alive or attenuated organisms, such as yellow fever or small-pox.

Malaise, fatigue, pallor, or weight loss.

What are the most common initial symptoms of chronic myelogenous leukemia (CML) patients?

CML

The initial symptoms are the presence of discomfort in the left upper quadrant or the accidental finding of a large spleen.

Splenomegaly

What is the most common physical finding in CML?

leukocyte

In CML, the spleen size is quite variable and correlates in a positive fashion with the height of the ____ count. No significant lymphadenopathy is present.

9 & 22; c-abl proto-oncogene (ABL); 9; 22; breakpoint cluster region (bcr); BCR-ABL

The Philadelphia chromosome was the result of breaks on chromosomes ____ & ____, with a reciprocal translocation that transposes the ____, from its normal location, on chromosome ____, to a new position on chromosome ____, in proximity to the ____. A new hybrid oncogene ____ is then formed. This new oncogene, presumably through its increased tyrosine kinase activity and inhibition of apoptosis of leukemic cells, has the potential to transform normal hematopoietic cells into CML cells and also plays a role in the progression to the acute blastic phase of the disease.

Philadelphia chromosome

The presence of what is virtually diagnostic of CML?

increased; 50:1; reduced or absent; increased; increased; increased; increased

In CML, leukocytosis is observed with ____ basophils & eosinophils, a myeloid-erythroid ratio of ____, ____ LAP activity, ____ serum B12/UBBC; ____ serum uric acid, ____ BMR (not related to thyroid function), & ____ serum LDH.

Absence of sternal tenderness, basophilia, eosinophilia, thrombocytosis, & splenomegaly

What suggests the presence of a leukemoid reaction rather than CML?

Other disorders usually have normal or increased LAP activity (vs reduced or absent) & lack Philadelphia chromosome

How is it possible to differentially diagnose CML from other myeloproliferative disorders?

Gleevec

Unique drug in that its effect is targeted to the molecular defect in CML, the bcr/abl fusion gene.

Fatigue or malaise for a few weeks or several months

What is the most common complaint at time of diagnosis in patients with acute myelogenous leukemia (AML)?

AML

Hemorrhagic phenomena is present in 50% or more of the patients.

AML

Bone pain and fever, usually secondary to infection, are the presenting symptoms in about 20% of patients.

AML

The primary physical findings relate to anemia (pallor, tachycardia, cardiac murmurs of hematologic origin) thrombocytopenia (petechiae and ecchymosis or other hemorrhages) and neutropenia (infection).

AML

Infiltration of the skin takes the form of diffuse plaque-like violaceous papular lesions.

Auer rods

What laboratory finding may be present in all types of AML?

Normochromic/normocytic anemia, reticulocytopenia, thrombocytopenia, auer rods, adequate BM aspirate

List the laboratory findings in AML.

Myelobast

What is the predominant cell in AML?

Cytogenetics

What is potentially the most important prognostic factor in AML?

The t(15;17), t(8;21), and inversions and translocations of chromosome 16.

What cytogenetic findings have been shown to have a favorable prognosis in AML?

Acute lymphoblastic leukemia (ALL)

Represents approximately 80% of cases of leukemia in children under 15-years of age, and accounts for 20% of adult acute leukemias.

ALL

Fatigue is a common presenting symptom accompanied by malaise and fever with or without infection. Hemorrhagic manifestations due to thrombocytopenia are common. Pain in bones and joints occasionally are severe enough to bring the patient to the physician. Symptoms related to lymphadenopathy or splenomegaly are also sometimes seen.

ALL

Physical findings relate to anemia (pallor, tachycardia, cardiac murmurs) thrombocytopenia (hemorrhage, petechiae and ecchymosis) and neutropenia (infection). CNS findings may also be seen as meningeal infiltration can occur.

ALL

Prophylaxis for central nervous system (CNS) leukemia (CNS irradiation and/or intrathecal methotrexate) is important in the management of ____ as the CNS is well known to be a site of relapse if prophylaxis is not given.

Methotrexate & 6-mercaptopurine

What are the major agents in maintenance therapy of ALL?

children

Bone marrow transplantation (BMT) in ____ with good prognostic factors is not indicated as the initial treatment of ALL because of the high success and curability rates obtained with chemotherapy. However, patients with high-risk disease or relapsed disease may benefit from it.

adults

Bone marrow transplantation in ____ should be considered in patients with high-risk cytogenetic findings or relapsed disease.

Burkitt type (L3)

Which type of ALL has recently been found to have an improved outcome when treated with regimens containing high dose cyclophosphamide and methotrexate?

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