During the holidays, Paul and I both took some time off from research. For one reason, we needed a mental break. Secondly, there isn’t much to decide until the donor is found. However, the last time we met with Dr. O’Brien, the head of the CLL department at MD Anderson, she mentioned that when the time came she was leaning toward Campath as my front line regimen. So I thought I would resume my research in preparation. WARNING: This may be boring. :)
Campath, also known as alemtuzumab, is a monocolonal antibody that targets an antigen known as CD52, a common antigen (protein) found on B and T cells (part of the body’s immune system) on the surface of mature lymphocytes but not on the stem cells from which these lymphocytes are derived. When the Campath antibody attaches to the CD52 antigen, the body’s immune system is activated to destroy these targeted cells in the blood and bone marrow. Since the CD52 antigen is also present on healthy B and T cells, treatment will temporarily weaken the immune system and care must be taken to protect against infection during treatment.
Campath works in an entirely different way from traditional chemotherapy, which kills rapidly dividing cells. Unfortunately, that includes healthy cells as well as cancerous ones. Since monoclonal antibodies target only specific cells, they may cause less toxicity to healthy cells. Monoclonal antibody therapy is usually given only for cancers in which antigens (and the respective antibodies) have already been identified.
Campath has been proven especially useful in cases with p53 deletions (ie. my 17p deletion), which are otherwise resistant to treatment. Campath is particularly important because it stays active in the body for a long time after it is given, which means it may work longer to prevent GVHD symptoms.
Possible side effects include 1) a reduction in blood counts (white and red blood cells and platelets), which can increase the risk for infection, anemia and/or bleeding; 2) infusion reactions such as fever, chills, nausea, rash, etc.; and 3) weakening of the immune system that can lead to serious infections. Less common side effects include cough, muscle pain, poor appetite, mouth sores, headache, numbness or swelling of hands and feet, dizziness, weakness, etc.
Dr. O’Brien also mentioned the possibility of a “mini-transplant,” also referred to as a non-myeloablative or reduced-intensity transplant. While there is nothing “mini” about the transplant itself, the pre-conditioning regimen is less toxic. A mini-transplant uses lower, less toxic doses of chemotherapy and/or radiation to prepare the patient for an allogeneic stem cell transplant. The use of lower doses of anticancer drugs and radiation eliminates some, but not all, of the patient’s bone marrow. It also reduces the number of cancer cells and suppresses the patient’s immune system to prevent rejection of the transplant. In a traditional myeloablative transplant, the goal of the conditioning regimen is to kill as many cancer cells as possible and to suppress the immune system of the patient to allow the donor cells to grow.
With the non-myeloablative transplant, cells from both the donor and the patient may exist in the patient’s body for some time. Once the cells from the donor begin to engraft, they may cause the GVL (graft vs. leukemia) effect and work to destroy the cancer cells that were not eliminated by the anticancer drugs and/or radiation. To boost the GVL effect, the patient may be given an injection of the donor’s white blood cells. This procedure is called a “donor lymphocyte infusion.”
The advantages of non-myeloablative transplants are that they are better tolerated. The disadvantages are that they rely mainly on the GVL effect.
The mini-transplant is not without risks. Some cells in the mixture given to patients also recognize healthy cells, thus triggering an undesired immune response called graft-vs.-host disease (GVHD), in which donor cells recognize the patient's healthy cells as foreign, sometimes resulting in destruction of healthy tissue. Survival rates among patients who receive a mini-transplant range from 30 percent to 70 percent, depending on the underlying disease, disease stage and whether the patient has other illnesses at the time of treatment.
The use of Campath, or alemtuzumab, following reduced-intensity conditioning and unrelated donor conventional transplantation has been associated with durable engraftment and significant reduction in GVHD but at the cost of impaired immune reconstitution and increased infectious complications.
For more information, as well as an interesting read, on stem cell transplants, visit the CLL Topics blog listed below.
With regard to donor updates, I spoke to my MUD Coordinator and learned a few new things. First, Paul’s HLA info came in and he was very disappointed not to be my match. I told him that he IS my match…just not for my bone marrow! F-42 has removed herself from the list. M-22 is again unavailable. A new M-24 who was also previously unavailable is now available and being sent a request. The best news was that a new M-47 has already had his blood test and MD Anderson has received it for testing. More on that in about a week. We still have the first donor option, F-22/13 of 14/with the DP antibody issue. I did learn that I have numerous DP antibodies, so the likelihood of finding a donor with no antibody issues is minimal. The “fix” for that is either Rituxan and/or plasmapheresis,
Plasmapheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells by a device known as a cell separator. The separator works either by passing the blood at high speed to separate the cells from the fluid or by passing the blood through a membrane with pores so small that only the fluid part of the blood can pass through. The cells are returned to the person undergoing treatment, while the plasma, which contains the antibodies, is discarded and replaced with other fluids. Medication to keep the blood from clotting (an anticoagulant) is given through a vein during the procedure.
So for now, the wait continues. My pain meds are keeping me at a fairly even keel, with only occasional increases in intensity. I still get tired and need my daily nap. I still push myself too much some days and then regret it the next…. I am trying to incorporate a little work to keep my brain occupied with something other than this and to see if a bit of extra income might come our way. I enjoy the kids and grandkids as often as possible. And I stay more and more in His word and before the throne.
I truly believe that God is in this and will bring me through.
“For it is God who is at work in you, both to will and to work for His good pleasure.” Philippians 2:13
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