Today, there are
several options to treat patients with Chronic Lymphocytic Leukemia (CLL). If
the patient does not have extreme symptoms, like swollen lymph nodes and
spleen shortly after diagnosis, the first step in treating CLL is the wait and
watch method. Instead of administering drugs immediately, the best approach is
to monitor blood cell count and to see if the disease worsens. Research studies
show that there is harm for waiting to begin active treatment because some
patients may not develop severe symptoms for an extended period of time, and
may not need any treatment at all. If the symptoms worsen, then active
treatment will begin, usually in the form of chemotherapy. The most common drug
used in CLL chemotherapy treatments is Fludarabine, a purine analog that helps
to inhibit the function of DNA polymerase and ribonucleotide reductase and
promote apoptosis or programmed cell death for cancer cells in the blood. When compared
to other drugs that may be able to function the same way, Fludarabine proved to
be more effective with higher response and remission rates in patients with
CLL.
An alternative
to chemotherapy and Fludarabine is targeted therapy. Targeted therapy is a method
of treatment in which a drug targets the leukemia’s specific genes or proteins.
One example of targeted therapy is the use of monoclonal antibodies. Rituximab,
one of the drugs that will be used in my Senior Research Project, is an
anti-CD20 monoclonal antibody that is able to attach to an a surface protein on
B cells, and can destroy CLL cells without harming normal B cells. Due to the
success that Rituximab has had, it has been used in combination chemotherapy with
Fludarabine.
Ibrutinib is
will also be used in my research project and is a kinase inhibitor (another
type of targeted therapy). A kinase is an enzyme found in both cancer cells and
normal cells. Ibrutinib targets Bruton’s tyrosine kinase which is very
influential in the growth of B cells. Ibrutinib is able to block this enzyme,
therefore destroying some CLL cells. In recent studies, Ibrutinib seems to be
more effective (higher response and remission rates) when combined with
Rituximab.
The
last drug to be used in this project is Methylprednisolone, a corticosteroid that
helps to prevent substances that promote swelling in the body to be released.
This can be extremely useful to help reduce swelling of the lymph nodes
(adenopathy) and the spleen. This steroid is mostly used in patients with Relapsed
CLL (CLL that has returned) and has shown to increase response rates in
Relapsed CLL patients when combined with Rituximab. If the patient does not
respond well to Methylprednisolone and spleen swelling persists, the patient will
most likely have to splenectomy (spleen removal).
Chemotherapy
and the other drugs discussed come with side effects, mainly nausea. If the
leukemia persists and a patient is resistant to a drug, he or she may need a
stem cell or bone marrow transplant where leukemic bone marrow is replaced with
specialized stem cells that mature into healthy bone marrow. This procedure can
be extremely painful and can also be unsuccessful often.
The
three drugs to be used in my research project have been tested and are used
currently. Rituximab has been combined with Ibrutinib and Methylprednisolone
separately and has shown success, but the three have not really been combined
in the treatment of CLL.
Hey Eric!
ReplyDeleteIf cancer cells mutate so quickly and the surface proteins can change, how are antibodies such as Rituximab able to identify the CLL cells?
Hey Eric!
ReplyDeleteIf cancer cells mutate so quickly and the surface proteins can change, how are antibodies such as Rituximab able to identify the CLL cells?
The CD20 antigen is found on almost all mature B cells. Rituximab only attacks that certain antigen, which leads to apoptosis. It does not affect any other cells other than B cells with CD20, so if the CLL cell somehow changes and the CD20 antigen is not available, then Rituximab is not useful. It doesn't even affect immature B cells that do not have the CD20 antigen on their surface so that they can mature and continue to fight diseases. Rituximab is not perfect in its treatment but it has shown some promise. The main idea is that it can only target B cells with the CD20 antigen those B cells may or may not be leukemic cells. I hope this answered your question.
ReplyDeleteIt did, thanks Eric! :)
ReplyDeleteRhod Minster is my name, I am really perplexed today, and I share this piece of good news with everyone reading. Brethren, I was diagnosed of shingles some months after I did a surgery, and I was having serious acute, painful inflammation of the nerve ganglia, with a skin eruption. It was very bad that my skin was gone, and I was almost giving up. The fact was I am very vulnerable because of my weak immune system. So this shingles really affected me. I was taking antiviral medicines after some time it got worst that I was diagnosed of post-herpetic neuralgia. And my doctor prescribed for me paracetamol and codeine which I was using but my condition was getting worst instead of getting better. Somehow, my grandson came home and said his girlfriend was cured of HSV by a herbal doctor whose name was given as Herbal Doctor Uwadia Amenifo. My grandson claimed that his girlfriend was cured by the said doctor with his herbal medicine, so he advised me to give this same herbal doctor a try. I remembered a word at that stage which says ‘there is no harm in trying’ so I decided to give this herbal doctor a try. My grandson help contacted him, and I spoke with him on the phone, and also explained to him in a message I sent to his email. So he assured me, and gave me a good hope that he will surely cure me of this ailment. So we concluded arrangement, and he prepared the herbal medicine, and shipped it to me. So I took it according to his directions. And the herbal mixture really worked for me. I was so surprise the way it worked for me, and in just two weeks, I was beginning to fully recover, and in just less than 2 months, I was fully recovered, and all my pains and inflammation are all gone. Brethren, today I am totally cured and I deem it fit to come here and let everyone know about my cure through the herbal process. Please if you are still suffering from this ailment contact the herbal doctor for your cure. His contact details are as follows Email (doctoruwadiaamenifo@gmail.com), phone number (+2349052015874). Wish you all quick recovery.
ReplyDelete