Chronic
Myelogenous Leukemia (CML)Symptoms: In the beginning
of the disease the patient may be asymptomatic. The diagnosis may be made during
a general check-up with a general blood screening test. A complete blood count
(CBC) would show the pathologist that something is wrong and a blood
smear would allow the pathologist to make a tentative diagnosis.
As
the lymphoblastic cells accumulate in the bone marrow and the lymph glands, the
patient would feel tired and weak, experience a loss of appetite and weight loss,
develop fever and night sweats and experience a feeling of abdominal fullness,
as well as bloatedness. In 60 to 70% the physician will find an enlarged spleen,
enlarged lymph glands throughout the body including inside the abdominal cavity
and along the aorta. This accounts for the symptoms. The prognosis is guarded
when skin rashes occur (skin invasion), high fever is present and lymph glands
are markedly enlarged. Tests: The blood test in
a patient without symptoms ( the earliest stage) will usually have a white blood
cell count of less than 50,000 per microliter. When the patient has symptoms,
this count may be in the 200,000 count, but could go up as high as 1 million per
microliter. A blood count like this should trigger hospitalization or at least
a referral to a hematologist. That specialist will order some further more specific
tests such as a bone marrow aspirate and bone marrow biopsy, which shows hypercellularity.
The leukocyte alkaline phosphatase is very low. One specific marker, the Philadelphia
chromosome, as mentioned before, is positive in almost all patients
(more than 95 %). If it is negative, but all other parameters are typical for
CML, then this is a Philadelphia negative CML with a prognosis that is much worse.
In the later stages of CML, when the bone marrow is crowded with leukemia cells,
thrombocytopenia (low platelets) and anemia (low red blood cell count) is found.
This is a poor prognostic sign.
Treatment
for Chronic Myelogenous Leukemia: Treatment in the past consisted
of chemotherapy initially, however the mortality rate did not improve with this
therapy, so it had to be abandoned. Instead, researchers found another therapy,
which is very encouraging: interferon therapy. This substance is normally produced
by white blood cells as a response to viral illnesses. At a high dose of 5 million
units per square meter body surface per day, given subcutaneously, remission rates
between 50% and 70% were achieved, which is good for such a bad disease as CML.
The goal nowadays is to continue interferon therapy until "cytogenic
remission" is achieved. This means that repeat blood test and bone marrow
aspirates are investigated with cytogenetics for the Philadelphia chromosome.
If the therapy has wiped out the abnormal leukemia cells and normal bone marrow
and blood cells have reoccurred, the long-term survival is much better than if
this could not be achieved. One large study showed that the 5 year survival is
as follows for patients with complete cytogenic remissions versus those with only
partial remissions:
5-year
survival in chronic myelogenous leukemia (CML)
| | C
y t o g e n i c R e m i s s i o n |
| Complete: | Partial: |
| 70% | 15% |
There have been many trials in an attempt to improve the partial
remission rate and convert this to a complete remission rate. However, there are
many confusing details about this. The bottom line is that the earlier the CML
has been diagnosed, the better the prognosis and the more successful an early
treatment protocol will be. Hydroxyurea is a chemotherapy drug, which had some
success with CML. This in combination with interferon has given slightly better
results (about 10%) than interferon or hydroxyurea alone. However, there is a
toxic side effect to hydroxyurea, which has to be balanced against the beneficial
effect. Some more data on prognosis of CML: Interferon prolonged the median
survival from 3.5 years following the initial diagnosis of CML to about 7.0 years.
About 5 to 10% of patients die within 2 years after the diagnosis. Each year thereafter
about 10 to 15% die per year. However, 90% of patients will die following a blast
crisis or accelerated phase of CML. What's behind it is the total tumor mass and
how this mass of CML leukemia cells behaves in terms of consuming the healthy
body. It is like a forest fire out of control inside the body. Once cytogenic
remission has been achieved, it is like the fire has been extinguished. Unfortunately
at this point in time this is only achievable in the minority of cases. After
a blast cell crisis median survival is only about 2 months. Approximately 25%
of patients at this stage will go into remission with treatment. If they do, then
survival may be extended to about 10 months. A newer development is the
introduction of tyrosine
kinase inhibitors into the armamentarium of chemotherapy. See this
link for a brief review. Bone marrow transplant (BMT): As
explained in the beginning of this chapter the problem with CML is that a clone
of leukemia cells took over that had originated from one stem cell, which had
a chromosome translocation (Philadelphia chromosome). The only way to cure that
condition permanently is to eradicate the abnormal cells and to replace the old
bone marrow with a bone marrow transplant (BMT), which is disease free. As explained
earlier, this was first pioneered with childhood ALL. This works also for
adult CML patients and is the only hope for long-term survival and even cure.
There is a body of world wide experience with BMT and the following few comments
will sum this up. After several thousand BMT's it is clear that the best results
are obtained when a BMT is done in the chronic phase (not during a blast crisis).
Patients who are young and whose CML has been diagnosed less than 1 year before
the BMT was done, show the best results. With a close family match for BMT the
5 year survival may be as good as 50 to 60%. However, if this is not available,
a closely matched BMT from a non related donor can achieve a survival rate of
45% around 2 years. There are many unanswered questions, but hopefully new answers
will be available to these by newer research.
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