Why Ph+ CML Treatment Can Stop Working

Most of the time, people with CML respond very well to treatment. And the better the response, the more likely that they will keep their CML under control for years with no change in treatment.

In rare cases, however, treatment does not produce a complete response, or the response does not last. This can happen because:

Not enough of the drug is getting into the blood stream or into the cancer cells (This can happen even if you are taking your medication as directed)
The cancer cells have developed other mutations that allow them to keep growing (See figure below)

In these cases, the doctor may monitor your treatment and order tests. Depending on the test results and what treatments you may have already received, the doctor may then decide to either:

Increase the dose of your current treatment
Switch to a different treatment option , such as another TKI, stem cell transplantation (SCT), interferon-alpha (IFN), or hydroxyurea

How Mutations Can Lead to Treatment Progression

BEFORE
TREATMENT

Abnormal cells with Ph
chromosome multiply and
crowd out healthy cells

AFTER 3 TO 6
MONTHS OF
TREATMENT

Treatment stops growth of
abnormal cells, and healthy
cells begin to return

IN COMPLETE
CYTOGENETIC
REMISSION

No abnormal cells are seen
but a tiny number may
remain undetected.

POSSIBLE CHANGES OVER TIME

No change; Cells
remain normal

Cells with Ph
chromosome mutate
and begin to grow

Cells without the Ph
chromosome develop
other mutations

LONG-TERM OUTCOME

In most patients,
CML remains in
remission for years,
with no change in
treatment

In a few patients,
CML returns and/or
gets worse; a
change in treatment
is needed

In rare instances,
these other
mutations may lead
to acute leukemia
or another blood
disorder, requiring
a change in
treatment

Connect with other
Ph+ CML patients

Hydroxyurea

Hydroxyurea is a chemotherapy drug.
Chemotherapy drugs act by killing all
fast-growing cells including both abnormal and normal cells. Hydroxyurea can be given to treat some symptoms of CML. It is generally given at diagnosis to lower WBC count, particularly when WBC at diagnosis is very high. It has not been shown to cure CML or help people live longer.

Interferon-alpha

Interferons are natural substances made by the body. They are also referred to as biologics. Injections of interferon-alpha may help slow down the growth of leukemia cells and help some people live longer, but they have not been shown to cure CML. Interferon-alpha can often make many people feel very sick (flu-like symptoms).

Stem cell transplantation (SCT)

Stem cell transplantation involves two
steps:

1. Killing most of the cells in the bone marrow (cancer cells and healthy cells) with a very high dose of one or more drugs

2. Replacing the destroyed cells with only healthy cells that are taken from another person who does not have CML. The healthy cells settle into the bone marrow where they start to grow and make normal blood cells.

For this treatment to be successful, the donor's cells must match the recipient's cells very closely. Unfortunately, finding a matched donor is often difficult. The procedure can be risky, but it may be the right choice for some people. Stem cell transplantation has been shown to cure CML in some patients.