Acute Leukemia Flashcards
What is acute leukemia and how do patients present? How does it defer from chronic leukemia?
- acute leukemia is the neoplastic proliferation of immature lymphocytes (blasts) due to a disruption in the ability of these cells (myeloid stem cells and lymphoblasts) to mature
- patients present with the sudden development of anemia (fatigue), thrombocytopenia (bleeding), and neutropenia (fever); AKA pancytopenia
- this differs from chronic leukemia, which is the neoplastic proliferation of mature lymphocytes, and has a more insidious onset (largely asymptomatic)
- leukemias in general will present with pancytopenia, hepatosplenomegaly, generalized lymphadenopathy (the latter two are rare in AML, but common in ALL)
What percentage of cells in the bone marrow must be blasts in order for the diagnosis of acute leukemia to be made?
- more than 20%
- (the normal percentage is 1-2%)
What is AML? ALL? What are they key markers for each?
- AML: acute myeloid leukemia (myeloid stem cells accumulate); key marker of myeloid stem cell is MPO (myeloperoxidase), which crystallizes to form Auer rods in the cell
- ALL: acute lymphoid leukemia (lymphoblasts/lymphoid stem cells accumulate); key marker of lymphoblasts is TdT (terminal deoxynucleotidyl transferase; a DNA polymerase) in the nucleus
Which age group is most commonly affected by ALL? Which syndrome is ALL also associated with? What are the two types of ALL and which is more common? What markers are used to differentiate the two?
- ALL most commonly affects children (less than 15)
- it is associated with Down syndrome (arises AFTER the age of 5)
- 2 types of ALL: B-ALL (more common) and T-ALL
- B-ALL classically expresses CD10, CD19, and CD20
- T-ALL classically expresses markers between CD2-CD8
Which cytogenetic abnormality may drive B-ALL in children? What about in adults?
- children: t(12;21); has a good prognosis and responds very well to chemo
- adults (very rare): t(9;22); the Philadelphia chromosome; has a poor prognosis
How does T-ALL present?
- T-ALL presents as a Thymic mass in Teenagers
- because of the thymic mass, T-ALL is actually a LYMPHOMA rather than a leukemia (so it’s really an acute lymphocytic lymphoma)
- T-cell disorders commonly involve the skin
- (see cards in “Lymphomas”)
Which age group is most commonly affected by AML? What are the some of the major subtypes of AML?
- AML most commonly affects older adults (30-60)
- some subtypes (there are more): acute myeloblastic leukemia with minimal differentiation (M1; the MC); acute promyelocytic leukemia (M3 subtype), acute monocytic leukemia (M5), acute megakaryoblastic leukemia (M7)
What cytogenetic abnormality drives acute promyelocytic leukemia? What receptor is disrupted? What do these patients have a high risk of developing? How do we treat this leukemia?
- (this is the M3 subtype of AML)
- driven by t(15;17), which disrupts RAR (the retinoid acid receptor), resulting in the loss of ability of myeloid stem cells to mature
- this type of AML has a very large number of Auer rods (crystallized MPO), and so patients have a high risk of developing DIC
- treat acute promyelocytic leukemia with ATRA (all-trans retinoid acid), which binds to the disrupted RAR and triggers maturation; because of this, M3 has a favorable prognosis
What characterizes acute monocytic leukemia and acute megakaryoblastic leukemia?
- (these are subtypes of AML)
- acute monocytic leukemia (M5) is an accumulation of monoblasts (precursor to monocytes), which LACK myeloperoxidase (MPO) and thus lack Auer rods; it classically infiltrates the gums
- acute megakaryoblastic leukemia (M7) is an accumulation of megakaryoblasts (precursor to megakaryocytes), which also LACK MPO and Auer rods; it is associated with Down syndrome BEFORE the age of 5
Which acute leukemias are associated with Down syndrome?
- before the age of 5: acute megakaryoblastic leukemia (a type of AML)
- after the age of 5: ALL (larger association)
What is infectious mononucleosis? What is the most common cause? How do patients present?
- infectious mononucleosis (AKA “glandular fever”) is a lymphocytic leukocytosis of reactive atypical CD8+ T-cells due to an infectious agent (the T-cells become atypical in presence of EBV; they resemble macrophages)
- MCC is EBV; less commonly, via CMV
- patients present with generalized lymphadenopathy, fever, pharyngitis, splenomegaly, malaise, fatigue
- it is largely self-limiting; only give steroids if absolutely necessary (steroids may increase the risk of developing lymphoma via EBV)
How do we diagnose mononucleosis? What are some major complications of this disease?
- screen with monospot test (this detects the IgM heterophilic antibodies that develop in EBV infection)
- confirm with an EBV viral capsid antigen test
- complications: splenic rupture, maculopapular rash with penicillin (aminopenicillins especially), increased risk of lymphoma (the virus remains dormant in B-cells)
Which areas of the body are at particularly high risk of involvement with ALL?
- ALL can classically involve the CNS (always do a lumbar puncture at the time of Dx to see involvement) and testes
Does CML develop into ALL or AML? What about CLL? What else can progress into AML?
- CML can progress into both: of those that will transform, 2/3 of CML progress to AML, while 1/3 progress to ALL
- unlike CML, CLL rarely progresses to an acute phase
- myeloproliferative disorders (in addition to CML) can also progress to AML
