Heme/onc part 2 Flashcards
What are more than 90% of the cases of CML due to?
Philadelphia chromosome
Translocation of the long arm of chromosome 22 and 9
Results in the shortening of chromosome 22
Presentation of CML
Usually discovered incidentally with leukocytosis on CBC
Many times pts will have splenomegaly on PE
CML
CML can transform into acute leukemia, will see an increase in blasts and new chromosomal abnormalities
S/sx of CML
Low-grade fever Splenomegaly Decreased appetite Chronic fatigue Wt loss Excessive sweating
CBC findings of CML
Elevated WBC (20,000-60,000)
Lymphocyte count will be nl
Will usually see an increase in other granulocytic cells (basophils, eosinophils, etc)
Other lab findings of CML
Could have low or absent ALP
Leukocyte alkaline phosphatase (LAP) stains very low to absent in most cells, resulting in a low score
BMBx: hypercellular (many myeloid cells seen, such as basophils, neutrophils, eosinophils)
Stage of CML
Dz is biphasic, sometimes triphasic
Chronic phase
Accelerated phase
Acute phase (blast phase)
Tx of CML
Gleevec is the 1st line chemotherapy. It targets the BCR/ABL gene by inducing apoptosis in cells pos for BCR/ABL
Usual dosage is 400 mg PO daily
Bone marrow transplant is currently the only known cure for the dz
When does ALL most commonly occur?
In childhood
S/sx of ALL
Pallor Fatigue Joint pain Fever Wt loss SOB Persistent and frequent infections Gingival bleeding LAD and hepatosplenomegaly is common in ALL, as the lymphocytes are the involved cell lineage
PE of ALL
Petechiae Pallor Gingival edema Chloroma (mass of leukemic cells found outside of the bone marrow) LAD Testicular edema
Lab evaluation of ALL
CBC will reveal elevated WBC with lymphocytosis
Bone marrow bx will reveal leukemic blasts
CXR may revieal a mediastinal mass
Cytogenetic studies
-Translocation 12:22; most common and favorable prognosis
-Philadelphia chromosome is unfavorable prognosis in ALL
Tx of ALL
Induction and consolidation chemotherapy
>50% of children will be cured with chemo
Prognosis depends upon WBC and age at the time of dx
Chronic lymphocytic leukemia
Most common adulthood leukemia
Affects the B-cell lineage
Characteristics of CLL
Most pts are asymptomatic when discovered
CBC reveals leukocytosis, with predominant lymphocytes
-Must persist for >3 mos for dx
Further evaluation of CLL
Peripheral blood flow cytometry: Usually express CD19
FISH for CLL and cytogenetic studies: evaluates chromosomes 6, 11, 12, 13, 14, 17, 18, or 19
-Used as a prognostic indicator
If significant LAD present, needle bx should be obtained
Peripheral blood smear of CLL
Smudge cells present
S/Sx of CLL
Enlarged lymph nodes, liver, or spleen Recurring infections Loss of appetite or early satiety Abnl bruising (late-stage sx) Fatigue Night sweats
Tx of CLL
Early stage CLL is monitored closely. Routine CBCs performed q3-6 mos. Flow cytometry is performed about q6 mos
-Absolute monoclonal B-lymphocyte count <5000
-Lymph nodes <1.5 cm
-No anemia or thrombocytopenia
As dz progresses, chemo is necessary
-FCR is generally 1st line tx in pts <70 yo
–Fludarabine, cyclophosphamide, Rituxan
How are NHL tumors characterized?
By the level of differentiation, the size of the cell of origin, the origin cell’s rate of proliferation, and the histologic pattern of growth
S/sx of NHL
B sx
- Fever
- Night sweats
- Wt loss
Low-grade NHL
Generally are felt to be slow-growing indolent diseases
Treatable with chemo but not curable
Pathologically described as grade 1 follicular or small lymphocytic lymphomas
Typically older pts- usually feel well, generally have no sx, and often have their dz found incidentally in the workup of another medical problem
Pts can often live up to 10+ years without requiring tx with chemo
Intermediate grade NHL
More aggressive
Can be found in both young and older pts
They are usually grade 2 or 3 and consist of the more common subtypes
-Diffuse large B cell, mantle cell, and follicular lymphomas
Pts usually are experiencing some or all of the B sx
This is very curable, even in pts with stage 3 or 4 dz
Tx should be started ASAP
High grade NHL
The most aggressive
Generally present in the younger, adolescent pt population
Pathologically, they include types such as Burkitt’s lymphoma, T-cell lymphomas, and anaplastic lymphomas
CNS involvement can commonly occur
Pts are often symptomatic at the time of presentation, and again, tx should start ASAP
Tx of low-grade NHL
Chemo initiated with progressive dz and bulky LAD
Usually tx with CHOP: Cyclophosphamide, hydroxydaurnorubicin, Oncovin, prednisone
-Chemo treatments do not have to be as aggressive in this situation
Adjuvant tx to chemo in NHL
Rituxan, which is targeted therapy to inactivate CD20+ lymphoma cells
Given with the second cycle
Often used once chemo is complete as maintenance therapy is given every 3-6 mos
Tx of intermediate/high grade NHL
If early stage I or II dz, can sometimes treat with radiation only, depending on type of lymphomas and site of involvement
Otherwise, will need to treat with chemo +/- Rituxan
Characteristics of Hodgkin’s lymphoma
Characterized by Reed-Sternberg cells
EBV is related in 40-50% of cases
Usually arises in one lymph node group and spreads to other nodes
Subtypes of Hodgkin’s lymphoma
Nodular sclerosis
Mixed cellularity
Lymphocyte depleted
Lymphocyte rich
Incidence of Hodgkin’s lymphoma
Bimodal incidance of Hodgkin’s with the first peak in pts in the twenties and the second peak after the age of 50
Most children with the disease are males
Clinical features of Hodgkin’s lymphoma
`Painless cervical, supraclavicular, and mediastinal LAD
B sx
Nodular sclerosis subtype is usually seen in young women
B sx
Night sweats Intense pruritis Unexplained fever Unintentional wt loss Fatigue and generalized weakness
Tx of Hodgkin’s lymphoma
Early stage disease I or II can often be treated with radiation alone or a combination of short course chemo and involved field radiation therapy
Stage III or IV dz is treated with chemo
If there is bulky mediastinal involvement, radiation to the chest may also be done
What should be done for pts that relapse after first line Hodgkin’s lymphoma tx?
Additional chemo is recommended along with auto stem cell transplant which can also afford long term survival and possible cure
What is the most common hematologic malignancy in the African American population?
Multiple myeloma
What is oftentimes the first presentation of multiple myeloma?
Hypercalcemia
Lab work for multiple myeloma
CBC
Chemistries- including total protein, albumin, and calcium levels
Immunofixation studies from serum and urine
Immunoglobulin levels- IgG
Skeletal survey
Bone marrow bx
Radiographic studies to evaluate specific areas of pain
Lab findings of multiple myeloma
Routine CBC may often shown anemia and/or thrombocytopenia
High total protein level, high calcium and an elevated creatinine
Skeletal survey will show classic signs of lytic lesions in the bone
A bone marrow bx that shows more than 20% plasma cells is usually diagnostic for multiple myeloma
Stage I multiple myeloma
Pts must have all of the following along with a bone marrow bx showing <20% plasma cells:
- Hgb >10
- Serum calcium nl or <12
- Relatively small amount of monoclonal immunoglobulin in the serum or urine
- Skeletal survey nl or with solitary plasmacytoma
Stage II
Pts who qualify for neither stage I nor III
-A moderate number or myeloma cells are present
Stage III multiple myeloma
Pts that have any one of the following along with bone marrow bx showing >20% plasma cells
- Hgb <8.5
- Serum calcium >12
- High M component in serum
- UPEP M component >12 gm/24 hr
- Extensive lytic lesions
Tx of multiple myeloma
High doses of decadron is still a mainstay of tx
-Combined either with oral biologic agents such as Thalidomide or Revlamid or intravenous chemo agents
Some pts may qualify for high dose chemo and autologous stem cell transplant, depending on their age and extent of dz
Tx of hypercalcemia and lytic bone lesions in multiple myeloma
IV chemo agents and bisphosphonates
Usually Zometa 4 mg IV q4 wks
Kyphoplasty in multiple myeloma
A procedure done by neurosurgeons or orthopedic surgeons to stabilize vertebral bodies that have been compromised
F/u of multiple myeloma
Pts should be monitored every 2-3 mos with repeat lab work to determine response to dz
- SPEP/IPEP, IgG
- A repeat bone marrow bx would be indicated if new lab abnormalities were to develop
