acute leukemia Flashcards
What is acute leukemia? What are the defining symptoms and diagnostic landmarks?
this is an acute proliferation of immature blasts.
it its characterized by > 20% blasts in the bone marrow. Blasts are immature cells with large nuclei and “punched out” nucleoli.
blasts in the bone marrow crowd out other, normal cells, and cause thrombocytopenia (pt bleeds), anemia (pt fatigued) or neutropenia (infection).
blasts often spill into the peripheral blood, causing a high white count.
separated into acute myelogenous or acute lymphoblastic leukemia, depending on subtype
acute lymphoblastic leukemia: what is it? important markers, patient population
this is an acute leukemia of lymphoblastic cells. lymphoblastic cells are TdT positive. TdT is a DNA polymerase that is NOT found in mature lymphocytes or in myeloid blasts.
acute leukemia is commonly seen in kids. associated with trisomy 21 after the age of 5.
subdivided into B-ALL and T-ALL
B-ALL: important markers, treatment, prognosis, presentation
most common type of ALL. These are TdT + blasts (TdT is a DNA polymerase) that also express CD10, CD19, and CD20.
must give prophylaxis to the scrotum and the CSF, as chemo drugs won’t get there easily.
prognosis is based on chromosomal translocations: 9,22 translocation is usually seen in adults and has a poor prognosis. 12;21 translocation seen in kids and has a good prognosis.
T-ALL: important markers, presentation
TdT positive (TdT is a DNA polymerase). CD10 negative. may express markers from CD2-CD8. often presents in teenagers as a thymic mass.
acute myeloid leukemia: general characteristics, markers, typical patient
> 20% blasts in the bone marrow. blasts are myeloperoxidase positive (exception: acute monocytic leukemia, acute megakaryoblastic leukemia). myeloperoxidase may precipitate as Auer rods. usually arises in older adults; may arise from pre-existing dysplasia (myelodysplastic syndromes), though most patients with myelodysplastic syndromes die of infection or bleeds rather than AML.
subdivided based on cytogenetic abnormalities, lineage of myeloblasts, and markers.
acute promyelocytic leukemia: problem, clinical manifestations, treatment
proliferation of immature granulocytes, called promeylocytes. M3 subset is due to a 15;17 translocation that disrupts the gene for the retinoic acid receptor. RAR is normally on chromosome 17 but is wrongly translocated on chromosome 15. This disruption prevents binding of retinoic acid to the receptor, and the cells can’t mature. immature, abnormal promyelocytes pile up. Abnormal romyelocytes contain many primary granulocytes, which increases the risk for DIC. may be induced by chemo as Auer rods are released.
treatment is ATRA. this binds the altered RAR and causes maturation and eventual death of the blasts.
acute monocytic leukemia
proliferation of monoblasts. usually lack MPO.
blasts characteristically infiltrate gums
acute megakaryoblastic leukemia
proliferation of megakaryoblast. lack MPO. associated with Down syndrome before the age of 5.
AML from pre-existing dysplasia. causes of pre-existing dysplasia, presentation of dysplasia.
pre-existing dysplasia often seen with exposure to alkylating agents or radiotherapy.
myelodysplastic syndromes usually present with cytopenias, hypercellular marrow, abnormal cell maturation ,and increased blasts (<20%). most pts die from infections or bleeds, but some progress to acute leukemia.
What are the general principles behind a chronic leukemia?
proliferation of mature circulating lymphocytes characterized by a high WBC count. usually insidious and seen in older adults.
chronic lymphocytic leukemia: markers, diagnosis, clinical features
also called small lymphocytic lymphoma if it involves the lymph nodes.
neoplastic proliferation of naive B cells that coexpress CD20 and CD5. often see smudge cells on blood smear.
3 important complications:
1. hypogammaglobulinemia: INFECTION is the most common cause of death in CLL.
2. autoimmune hemolytic anemia
3. transformation to diffuse large B cell lymphoma. marked clinically by an enlarging lymph node or spleen
hairy cell leukemia
this is a neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes. it is TRAP positive (tartrate-resistant acid phosphatase).
features: splenomegaly (cells accumulate in the red pulp- weird), and “dry tap” on marrow aspiration d/t marrow fibrosis. LAD not usually present.
excellent response to 2-CDA (cladribine), an adenosine deaminase inhibitor. adenosine accumulates to toxic levels in neoplastic B cells.
adult t-cell leukemia/lymphoma
neoplastic proliferation of mature CD4 T cells.
related to HTLV-1; most common in Caribbean and Japan. features: rash, generalized LAD with hepatosplenomegaly, and lytic bone lesions with hypercalcemia
mycoides fungoides
neoplastic prolif of mature CD4 T cells that infiltrate the skin, producing a localized skin rash, plaques, and nodules. aggregates of neoplastic cells in the skin are called Pautrier microabscesses. cells may spread to involve the skin: see lymphocytes with cerebriform nuclei (Sezary cells) on blood smear.
