Leukemias and Lymphomas by N7vJp41

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									Biology 207                                       Spring 2004
Biology of Cancer

Lecture 14: "Leukemias and Lymphomas"

Readings: King pp. 279-283;29-30
          R-Landro OR INT-NCI bone marrow transplants

Other sources: Leukemia and Lymphoma Society web site

Outline:
1. Definitions
2. Major types of leukemia and lymphoma
3. CML
4. Treatment options: Bone Marrow Transplant

Lecture:

1. Definitions

Leukemia: cancer of the bone marrow and blood

Lymphoma: cancer of the lymphatic system. Usually solid tumors.

Myeloma: cancer of plasma cells--white blood cells that make antibodies.
Patients susceptible to infections.

2. A. Leukemia types:

myeloid=myelogenous leukemia: cancers of certain white cells (granulocyte and
monocyte precursor cells).

lymphocytic: cancers of lymphocyte precursors.

can be either acute (rapid progression, symptoms occur in days or weeks)
or chronic (progresses more slowly, over months or years)

slow progressing cancers that are difficult to treat = indolent

Common types

      ALL: Acute lymphocytic leukemia
      AML: Acute myelogenous leukemia
      CML: Chronic myelogenous leukemia




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B. Lymphoma types:

Hodgkin’s disease: Unusual cell type observed “Reed-Sternberg cell” which
causes disease.

non-Hodgkins lymphomas (usually classed based on cell of origin--”Rappaport
classification”)
example: Burkitt’s lymphoma, caused in Africa by Epstein Barr virus

C. Statistics:
    109,500 people in US diagnosed with leukemia, lymphoma and myeloma
      this year.
    11% of deaths from cancer in 2001.
    Leukemia is most common form of childhood cancer.
    Leading fatal cancers in young men under 35.

D. Symptoms:
    Anemia
    Bleeding or bruising
    Bone and joint pain
    Abdominal distress
    Swollen lymph nodes

E. Diagnosis: A number of methods including
    Bone marrow aspiration or biopsy
    Blood tests: blood count, blood chemistry

3. Case example of a type of leukemia: CML = chronic myelogenous
leukemia

Two phases: chronic phase, blast crisis

Characteristic change in disease prior to blast crisis: Philadelphia chromosome
(chromosome rearrangement that gives small chromosome 22) when oncogene
is activated--fusion oncoprotein bcr-abl is produced.

Treatment options:

      Chemotherapy, especially interferon  and Gleevac
      Bone marrow transplant or umbilical cord blood transplant
      Radiation

Successful treatment measured by reduction/elimination of Philadelphia
chromosome in myeloid cells.




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New treatment based on inhibitor of activated oncoprotein

      Gleevac is an inhibitor of the bcr-abl tyrosine kinase.
      Approved by FDA in May 2001 for treatment of CML, newly approved for
       select gastrointestinal tumors.
      Induced a major response in 60% of patients and complete response in
       95%.
      Toxic side affects in 2% of patients resulted in discontinuing the drug.
      Effectiveness may be improved by combining with other drugs.

4. Steps in bone marrow transplant (allogeneic transplant) for CML:

Bone marrow: Hollow area inside bones where blood cells reproduce and
differentiate.

1. testing patient tissue antigens

2. chemotherapy, if needed to keep disease in check

3. match donor tissue antigens (twin or sibling if possible)

4. admission to transplant unit, Hickman line (6 months after diagnosis)

5. radiation and/or chemotherapy to kill patient’s bone marrow cells (including
cancer cells)

6. surgical removal of bone marrow cells from donor

7. intravenous infusion of cells from donor (Steps 5-7 took about 2 weeks in
hospital)

8. recovery/complications (many months)
       intravenous nutrition
       intravenous antibiotics
       intravenous blood or platelet transfusions as needed
       moniter graft rejection (graft vs. host disease)
       moniter for cancer cells (look for Philadelphia chromosome in certain
white cells, for CML)




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