Acute Leukemias Flashcards
acute myeloid leukemia (AML): demographics of affected patients, and prognosis
- 3 cases/100,000 people/year
- 65 y/o
- rare in children and young adults
- prognosis due to adverse risk cytogenetics and favorable risk cytogenetics
- Approximately 60% of AML cases will reach complete remission after chemotherapy
acute lymphoblastic leukemia (ALL): demographics of affected patients, and prognosis
- 1-5 cases/100,000/year
- mainly children <6 yo
- good prognosis in children
- worse prognosis in adults
Explain the concept of a “leukemic stem cell”
The most important aspect of the leukemic stem cell is that it has the potential for self-renewal. Thus, in patients with acute leukemia there is a population of cells that, in essence, provides an inexhaustible source of the leukemic cells that replace the bone marrow.
List risk factors for acute leukemia, while recalling that the majority of acute leukemias occur in the apparent absence of risk factors
A. Previous chemotherapy, especially DNA alkylating agents and topoisomerase-II inhibitors
B. Tobacco smoke
C. Ionizing radiation
D. Benzene exposure
E. Genetic syndromes including Down syndrome, Bloom syndrome, Fanconi anemia, and ataxia-telangiectasia.
List common signs and symptoms exhibited by patients with acute leukemia at initial presentation, and explain the reasons for these findings
The signs and symptoms of acute leukemia are related to decreased numbers of normal peripheral blood cells due to marrow infiltration by leukemic cells
Symptoms: fatigue, malaise, dyspnea, Easily bruised, weight loss, Bone pain or abd pain, Neurologic sx (rare)
Signs: anemia and pallor. Thrombocytopenia, hemorrhage, ecchymosis, petichiae, fundal hemorrhage, Fever and infection, Adenopathy, hepatosplenomegaly, mediastinal mass, Gum or skin infiltration, Renal enlargement and insufficiency, Cranial neuropathy
Immunophenotyping
the use of antibodies to detect whether certain substances are being expressed by cells. This allows us to place morphologically non-distinct cells, such as blasts, into a definite lineage
Basic markers: ALL
- Lymphoblasts often express CD34, a marker of immaturity also often expressed by myeloblasts.
- Lymphoblasts express TdT, a nuclear enzyme that is specific to lymphoblasts
- B-lymphoblasts express B-lineage antigens (e.g. CD19, CD22).
- T-lymphoblasts express T-lineage antigens CD3 and/or CD7.
Basic markers: AML
- Auer Rod
- By flow cytometry, myeloblasts often express CD34, a generic marker of immaturity that can also be seen in lymphoblasts.
- Myeloblasts also often express myeloid antigens, such as CD117 (C-Kit) , myeloperoxidase that allow them to be identified as myeloblasts.
Contrast B-ALL and T-ALL in regards to patient age and sex, manner of manifestation, and prognosis
-B = majority, T = minority
-In contrast to B-ALL, T-ALL more frequently occurs in adolescents and young adults than in children.
-In contrast to B-ALL, T-ALL more frequently present with a component of lymphoblastic lymphoma
(T-LBL), often manifesting as a large mediastinal mass.
-If the disease does have leukemic (T-ALL) component, the disease is more likely to present with a high white blood cell count than B-ALL.
-T-ALL / T-LBL favors males over females.
List 3 commonly observed cytogenetic abnormalities in B-ALL, and recall the usual patient age group and prognosis associated with these abnormalities
B-ALL with t(9;22)(q34;q11.2); BCR-ABL1:
- age: adult
- prognosis: the worst
B-ALL with translocations of 11q23; MLL:
- age: neonates and young infants
- prognosis: poor
B-ALL with t(12;21)(p13;q22); ETV6-RUNX1:
- age: childhood
- prognosis: very favorable
List 5 factors affecting prognosis in ALL
- age
- WBC
- slow response to therapy/small amounts of residual disease after therapy
- # of chromosomes
- B vs. T lineage (T has worse prognosis)
List 2 types of findings that would allow for a diagnosis of AML.
increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood (Dx: microscopic review of bone marrow aspirate smears or peripheral blood smears, flow cytometric review of marrow aspirate material or peripheral blood, microscopic review of the marrow core biopsy)
-The typical morphologic appearance of a myeloblast is generic, and these cannot be reliably told apart from lymphoblasts by morphology alone, unless one sees an AUER ROD.
Recognize an Auer rod, and relate its clinical significance
Auer rods are fused azurophilic granules forming small stick-like structures in the cytoplasm. The presence of Auer rods allows the identification of a blast as a myeloblast. Furthermore, they are only seen in abnormal myeloblasts.
Recall the associated prognosis for the 5 recurrent cytogenetic abnormalities for AML listed in the notes, and recall their typical patient populations if one is listed
1) AML with t(8;21)(q22;q22); RUNX1-RUNX1T1:
- patient population: younger patients
- prognosis: relatively good prognosis
2) AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11:
- patient population: younger patients
- prognosis: relatively good prognosis
3) Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA:
- prognosis: better remisison rates with ATRA/arsenic therapy
4) AML with t(1;22)(p13;q13); RBM15-MKL1:
- patient population: infants with Down Syndrome
- prognosis: relatively good prognosis
5) AML with abnormalities of 11q23; MLL:
- prognosis: poor prognosis
Explain two reasons why it is important to recognize at initial diagnosis that a case of AML is the AML with t(15;17)(aka acute promyelocytic leukemia (APL)) subtype of AML
1) The gene fusion in APL fuses the retinoic acid receptor-alpha (RARA) gene to another gene. RARA is needed for differentiation of promyelocytes; the fused product does not work well and leads to a block in differentiation. However, the block can be overcome with supra-physiologic doses of all-trans retinoic acid (ATRA), in combination with arsenic salts. Thus, these patients can be treated with ATRA/arsenic, and do not require traditional induction chemotherapy, which would be used for most AMLs. This is important as traditional induction chemotherapy has much higher rates of morbidity and mortality than ATRA therapy. With ATRA/arsenic therapy, APL still has better remission rates than any other type of AML.
2) Some cases of APL give rise to disseminated intravascular coagulation (DIC). Thus, it is important to recognize APL so that the clinician may know to be on the look-out for potential DIC.
