Adult Leukemia Introduction:
There are three major forms of adult acute leukemias. They are
called acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and
acute undifferentiated leukemia (AUL). AML is 5 times more common than ALL and
AUL is less common than ALL. The distribution of %-ages differs somewhat from
region to region. The cause of leukemia in adults is similar as stated
above for childhood leukemias and much about it is still unknown. Secondary leukemia
due to a longterm chemotherapy side effect is more common in adults than in children.
Exposure to industrial poisons (benzene e.g.) or exposure to ionizing radiation
are more common in adults. Also there are certain regions such as Japan or the
Caribbean where a certain leukemia virus (human T-cell
leukemia virus) causes a special type of leukemia. This is the only
known human virus that is known to cause leukemia apart from the Epstein-Barr
virus, which is known to cause Burkitt's lymphoma in Africa. Secondary
leukemia: Chemotherapy regimens may save some
lives in many cancers such as leukemias, Hodgkin's lymphoma, myelomas, lymphomas,
ovarian cancer and breast cancer. However, one of the side-effects can be AML,
which is the common type that develops in such situations. The peak time when
such secondary leukemia develops is between 4 and 5 years after the original cancer
has been treated with chemotherapy, but fortunately only about 5 to 10% of patients
will have the misfortune to have this happen to them. This subgroup of AML have
more resistant leukemia cells as they have additional chromosome abnormalities
on top of the ones which are typical for leukemia. This translates into difficulties
with treatment regimens and much lower cure rates than the cure rates for primary
leukemia. Leukemia
symptoms: The symptoms of acute leukemia are non specific fatigue
and malaise. The degree of anemia, which originates from a replacement of precursor
red blood cells in the bone marrow, will determine the degree of fatigue. Most
of the patients will have had leukemia for less than 3 months(only about 25% for
more than that) when fatigue is pronounced. Air hunger and rapid breathing, infections
and bleeding are common symptoms. Minor colds and flu-like symptoms are common.
Persisting fever without any obvious cause is found frequently. Bleeding into
the skin as pin like dots("petechiae")
or in form of larger areas of the skin ("multiple echymosis") are found
more commonly in AML. The degree of this bleeding is directly linked to
the loss of platelets, the blood cells responsible for blood clotting. This occurs
as the leukemia cells accumulate in the bone marrow suppressing the precursors
of the platelets there. Other symptoms can be gum infection and throat
infection. The physician might notice more subtle infections around the anal area
or in the soft tissues. In ALL liver enlargement and spleen enlargement as well
as lymph gland swelling tell the physician that the diagnosis likely is leukemia.
In AML and AUL these signs may not be as prominent. The final diagnosis is always
made after extensive tests. Some more peculiar initial presentation can be a strange
skin rash, particularly in AML where skin infiltration with leukemia cells is
more common. Chest bone pain (sternum pain) happens in about 50% of leukemia patients.
Leukemia
tests: As mentioned before, a meticulous work-up with further tests
is necessary to evaluate the patient. This will initially involve blood
tests and when there are gross abnormalities such as the constellation
of high white blood cell count, low platelet count and low red blood cell count
(anemia), a bone marrow aspirate and bone marrow biopsy
has to be done by a hematologist or internist. This material is then carefully
prepared with specific stains and viewed under the microscope by a pathologist
specialized in leukemia (cyto- and histopathologist). Most of the leukemias can
be clearly diagnosed this way. However, on some occasions the pathologist needs
to do further histological tests utilizing the electron microscope, further cytochemical
tests or immunological classification utilizing monoclonal antibodies. It would
be too overwhelming for the reader to go into more detail about these tests or
genetic tests that occasionally are also used.
The
purpose of all this testing is to ensure the following:
- initial diagnosis must be correct before treatment
- extent
of involvement of leukemia must be known
- are vital organs
involved?(liver, kidney, brain)
- is the leukemia confined
to the bone marrow?
- CNS involvement in childhood ALL
dictates a whole separate program to eradicate leukemia
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However, there are more rare subgroups of leukemia
, which are not included here that need specialized treatments. For this reason
it is extremely important to do these tests initially in a systematic manner.
Another reason to do tests is to rule out other causes that may mimic leukemia.
Physicians call this differential diagnosis. It is good
medical practice as in other clinical situations, to rule out other disease, which
could present with similar clinical features. For instance, tuberculosis, systemic
lupus, anemia due to folic acid deficiency or vitamin B12 deficiency are known
to mimic the bone marrow smear from a bone aspirate. However, a bone biopsy analyzed
with the special staining procedures mentioned above will differentiate each of
these causes. Finally there is a need to monitor the major body
functions throughout treatment with ongoing blood tests. For instance,
the high cell turnover of the rapidly dividing leukemia cells lead to elevated
uric acid, which is hard on the kidneys. An elevated blood uric acid level needs
to be brought down with allopurinol, a medication, which will ensure more uric
acid secretion into the urine. This will prevent the formation of kidney stones
when the chemotherapy treatment is started, as this in turn will lead to tumor
cell breakdown and uric acid increase in the blood. Another detoxification organ
is the liver. Liver function blood tests are done initially on during chemotherapy
to ensure that there is no deterioration and if there has been an initial abnormality,
that this hopefully will normalize with the treatment regimen. This is particularly
important in the case of infiltration of the liver by leukemia, as mentioned above
more commonly found in ALL. Leukemia treatment and prognosis: When
all the tests are done which classify the type of acute leukemia and tell the
physician what stage it is in, the treatment can begin. I will describe treatment
in general terms and then provide a few more details and prognostic features for
each subtype. Treatment of AML and ALL involves remission induction and
post-remission therapy as outlined above under childhood leukemias. There are
a few differences as mentioned below. Although there has been a major breakthrough
in the survival rate since the introduction of the combined chemotherapy regimens
in the 1970's as explained under childhood ALL above, progress in the 1980's regarding
leukemia survival rates for adult leukemia patients has been somewhat disappointing.
However, there are a number of factors for this, which are being further researched.
One key observation is that with adult leukemias the prognosis is poorest the
older the person is at the time of diagnosis. This has lead researchers
to interesting observations where differences could be found of the group that
does poorly when compared to the group that fares better. There are differences
in the mechanism of cell division, but also in the frequency of chromosome abnormalities,
chromosome breaks or and the absence of certain proteins that seem to suppress
the development of leukemia. These factors likely explain why the leukemia prognosis
for adults is poorer than for children. Such research will eventually lead to
much improved cures. Also, as the immune system ages, it is likely that this also
will be a powerful contributor to the worse prognosis in older people. I will
now describe some details regarding the three acute adult leukemias ALL, AML and
AUL (click on links in table
above). |
