Hematology Malignancies Flashcards
1
Q
leukemia
A
- Accumulation of Malignant white cells in bone marrow and blood
- They can cause symptoms from (1. bone marrow failure - Anemia, neutropenia, low platelet 2. Infiltration of organs - liver, spleen, lymph nodes, meninges, brain or skin)
2
Q
acute myeloid leukemia
A
- AML occurs in all age groups. Median age 67
- most common form of leukemia in adults
- Only comprises 10-15% of leukemia in childhood.
- Primary AML: arises de novo
- Secondary AML: Leukemia that develop from previous hematologic disorders or from previous chemotherapy for other cancers
3
Q
AML clinical features
A
- Profound anemia, thrombocytopenia
- Disseminated intravascular coagulation
- Tumor infiltration: (gum hypertrophy, skin involvement, CNS disease)
4
Q
treatment of AML
A
- Supportive care with transfusions
- Chemotherapy : Induction chemotherapy followed by consolidation chemotherapy
- ATRA/Arsenic for AML-M3 subtype
- Stem cell transplant
5
Q
Acute Lymphoblastic leukemia
A
- Most common form of leukemia in children, representing 80% of acute leukemia in children and 20% in adults
- 1 to 1.5 per 100,000
- Highest incidence is 3-7 years
- Second rise after age 40
6
Q
ALL clinical features
A
- Bone marrow failure (Anemia (pallor, lethargy, dyspnea), Neutropenia (fever, malaise, infections of mouth, throat), Thrombocytopenia ( bruising, bleeding gums))
- Organ infiltration (Tender bones, Lymphadenopathy, splenomegaly, hepatomegaly in 20% of patients, CNS involvement in 6%)
7
Q
ALL work up
A
- Decreased or increased WBC
- Peripheral blast
- Elevated LDH, uric acid
- Bone marrow blast present
- Lumbar puncture
- CXR may have enlarged mediastinal mass
8
Q
Treatment of ALL
A
-Chemotherapy (Induction chemotherapy followed by consolidation chemotherapy, Also includes CNS directed therapy to prevent or treat CNS disease, Maintenance for 2-3 years, Allogeneic transplant: indicated for Philadelphia chromosome positive ALL, primary refractory or early relapsed disease.
9
Q
chimeric antigen receptors: MOA
A
-Chimeric antigen receptors (Genetically engineered receptors that combine
anti-CD19 single chain variable fragment of an antibody with intracellular signaling domains of T cells, With the use of lentiviral-vector technology, CTL019 T cells express a CAR with CD3 zeta and 4-1BB (CD137) signaling domains)
10
Q
Chimeric antigen receptor (CAR) T cells
A
- genetically modified T cells
- patient’s own (autologous) T cells are manipulated ex vivo to express the antigen-binding domain from a B cell receptor that is fused to the intracellular domain of a CD3 TCR (CD3-zeta).
- recognition of a specific cell surface antigen activates T cell response
- CAR T cells have been studied most extensively in hematologic malignancies.
11
Q
Chronic myeloid leukemia
A
- Accounts for about 15% of leukemia
- May occur at any age
- Characteristic presence of Philadelphia chromosome.
- Translocation between chromosome 9 and 22 results in activation of tyrosine kinase.
12
Q
CML clinical features
A
- Male to female ratio 1.4 to 1
- Most frequently between ages 40 to 60, but may occur at any age
- Symptoms related to hypermetabolism: (weight loss, anorexia, night sweats)
- Splenomegaly is often present
- Anemia
- Bruising, epistaxis from platelet dysfunction
- In up to 50% the diagnosis is made incidentally from routine blood test
13
Q
lab findings of CML
A
- Increased WBC: usually >50k, usually see a complete spectrum of myeloid cells
- Increased basophils
- Normocytic anemia
- Platelet may be increased, normal or decreased
- Bone marrow is hypercellular
- PH chromosome positive
14
Q
Philadelphia Chromosome Translocation in CML Results in BCR-ABL Oncogene
A
- Stem cell disorder
- Characterized by myeloproliferation
- Well-described clinical course
- CML, chronic myeloid leukemia; Ph, Philadelphia chromosome; TKI, tyrosine kinase inhibitor.
- Chronic myeloid leukemia is one of the most important oncologic disorders and in part because it was the first oncologic disorder where a chromosome abnormality was identified. The Philadelphia chromosome is that specific chromosome abnormality. And as you can see from this cartoon, the Philadelphia chromosome is actually comprised of a balanced translocation between chromosome 9 and chromosome 22. This translocation brings the Abelson kinase together with the break cluster region and creates a fusion called the BCR-ABL. Importantly the presence of the Philadelphia chromosome gives this cell its proliferative advantage over normal cells and results in this chronic myeloid proliferative disease called chronic myeloid leukemia.
- It’s important to understand that this is a stem cell disorder so the translocation is located in early progenitor cells within the bone marrow compartment. It’s characterized by a proliferation, such that cells accumulate and patients with CML tend to have high blood counts at the time of their presentation.
15
Q
CML treatment
A
- Tyrosine kinase inhibitorsImatinib (Gleevec) (blocks tyrosine kinase activity , complete cytogenetic response >90%
- Nilotinib
- Desatinib (Chemotherapy, Interferon, Stem cell transplant: reserved for imatinib failure)
