Hematology Malignancies Flashcards
(35 cards)
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)
16
Q
B cell chronic lymphocytic leukemia
A
- Accumulation in the blood mature lymphocytes.
- Considerable overlap with lymphomas.
- Most common type of CLL, accounting for 20% of all leukemia in U.S.
- Peak incidence age 60 to 80
- Most common form of leukemia in the western world but rare in Far East
- Cells accumulate in blood, bone marrow, liver, spleen and lymph nodes as a result of prolonged lifespan and impaired apoptosis.
17
Q
CLL treatment
A
- Cures are rare so approach to therapy is conservative.
- Indolent disease, many patients never need chemotherapy
- Treat if symptomatic: organomegaly, hemolysis, bone marrow suppression
- Chemotherapy: chloroambucil, fludarabine, treanda, steroids
- Monoclonal antibodies: rituxan, campath
18
Q
Hairy cell leukemia
A
- Uncommon B cell lymphoproliferative disorder
- Represents 2% of leukemia
- Male: female ratio 4:1
- Peak incidence 40-60 years
- Clinical presentation: infections, anemia or splenomegaly
- Lymphadenopathy is very uncommon
- Pancytopenia is usual
- Peripheral blood show “hairy cells” , TRAP stain positive
- Treatments: 2 cda or pentostatin, achieves response in >80% patients, 2/3 no relapse occur.
19
Q
non-hodgkin’s lymphoma
A
- Incidence 17 in 100,000
- Very diverse group of disease: from very fast growing disease to very indolent disease.
- B cell lymphoma comprises 85% of cases
- T cell and NK cell together comprises 15% of cases.
20
Q
clinical features of non-hodgkin’s lymphoma
A
- Lymphadenopathy: Asymmetric painless enlargement of lymph nodes
- Constitutional symptoms: fever, night sweats, weight loss. Oropharyngeal involvement in 5-10%
- Infections
- Lab abnormalities: Anemia, neutropenia with infections, or thrombocytopenia, elevated LDH.
21
Q
workup of non-hodgkin’s lymphoma
A
- Diagnostic work up: Excisional lymph node biopsy
- Labs: CBC, chem panel, LDH, uric acid, serum protein electrophoresis
- Imaging for staging
- Bone marrow biopsy
22
Q
subtypes of nonhodgkin’s lymphoma
A
- Low grade non-Hodgkin’s lymphoma
- Follicular lymphoma (Most common form of NHL, Median survival about 10 years)
- Lymphoplasmacytoid lymphoma (Associated with elevated IgM)
- Mantle cell lymphoma
- Marginal zone lymphoma
- High grade non-Hodgkin’s lymphoma
- Diffuse large B cell lymphoma
- Burkitt’s lymphoma
- Lymphoblastic lymphoma
23
Q
T-cell lymphoma
A
- Peripheral T cell lymphoma
- Angiioimmunoblastic lymphadenopathy
- Mycosis fungoides
- Sezary syndrome
24
Q
hodgkin’s disease
A
- Clinical features:
- Can present at any age: peak incidence in young adults
- Mediastinal involvement in 6-11%
- Constitutional symptoms can be prominent
- classic types: nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte rich, Nodular lymphocyte predominant
25
treatment for hodgkin's disease
- Chemotherapy
- Radiation
- Both
- Late effects of Hodgkin’s disease and treatment can include secondary lung cancer, myelodysplasia, cardiac disease.
26
testing for hodgkin's disease
-CT/PET scans: Helpful in initial staging and disease assessment at completion of therapy. Unclear if CT/PET scans can guide therapy. Unclear if there is a role in monitoring after therapy.
27
multiple myeloma
-Neoplastic proliferation characterized by plasma cell accumulation in the bone marrow, the presence of monoclonal protein in the serum and or urine and related tissue damage
28
multiple myeloma clinical features
- Bone pain-resulting from vertebral collapse and pathological fractures
- Anemia: Lethargy, pallor, dyspnea
- Recurrent infections from deficiency of antibody production
- Renal failure
- Hypercalcemia
- Abnormal bleeding tendency
- Amyloidosis in 5%
29
diagnostic testing for multiple myeloma
- Lab tests: CBC, Creatinine, calcium, SPEP, UPEP, 24 hour urine for Bence jones protein, serum free light chain
- Bone survey
- Bone marrow biopsy
30
treatment for multiple myeloma
- Supportive: treat anemia, renal failure, hypercalcemia
- Chemotherapy
- Stem cell transplant
31
myeloproliferative disorder
- Bone marrow disorder characterized by clonal proliferation of one or more hematopoietic components in the bone marrow.
- Three disorders: Polycythemia Vera, Essential thrombocynthemia, myelofibrosis
32
polycythemia
- Excess production of red blood cells, but in over half of patients there is also overproduction of WBC and platelets.
- Clinical features: Headache, pruritus, facial plethora, splenomegaly, HTN. Gout can be a result of elevated uric acid.
- Positive JAK 2 mutation
- Serum epo level is low.
33
treatment of polycythemia
- Phlebotomy to maintain hct <45
- Hydrea can be used for patients who cannot tolerate phlebotomy, or has progressive splenomegaly, thrombocytosis.
- Interferon is another option. It is less convenient than oral hydrea.
- Median survival 10-16 years. Transition to myelofibrosis occurs in 30% pts, about 5% progresses to leukemia.
34
essential thrombocythemia
- Sustained increase in platelet count
- Hematocrit is normal
- Half of patient has JAK-2 mutation
- Clinical complications: thrombosis and hemorrhage
- Clinical symptoms: erythormelagia, up to 40% has splenomegaly
- Bone marrow biopsy shows increased megakaryocytes.
35
treatment of essential thrombocythemia
- High risk: patients over 60 years old, platelet >1000k, prior episodes of thrombosis or hemorrhage.
- Treatment: hydroxyurea and aspirin
- Low risk: patients < 60 years old, no previous thrombosis or hemorrhage, platelet< 1000k
- Treatment: aspirin
