St. Judes is a world class research Hospital. Dr. Tal Schechter-FinkelStein, our BMT doctor in Toronto went out of her way to get Maya down to St. Judes. And gosh, she really went out of her way! We’ve just returned from our initial consultation. We’ve had a battery of tests and had the opportunity to meet with everyone who will be involved in our care. Three of the doctors we’ve met are Dr. Brandon Triplett (Chief Investigator), Dr. Momcarz (fellow) and Dr. Pai (Radonc).
There are three main factors that have overall outcome; Disease Burden, GVHD and Relapse.
Smaller the burden going into BMT, better the outcome. It’s simple as that. Matter of fact, some patients are in complete remission and they still undergo the therapy.
Graft Vs Host Disease is a man made disease and come about as a result of the allogenic Translplant. Namely, putting in the donor’s blood into a patient causes the recipients body to violently object to the process. The donor’s blood and the recipients blood go to war with each other. If an acute GVHD develops, it is fatal. Until a few years ago, GVHD took up approx. 1/2 of the “Non Relapse Mortality”. The other common complications are due to infections.
GVHD is all about naive NK-Cells and the fine balance thereof. To a large extent, we need the selective NK-Cell functions.
- donor NK-cells should not attach the recipients tissues. (GVHD)
- donor NK-cells should attack recipients blood products. (GVTE, Graft Vs. Tumor Effect) This is the part that you do want. We want the donor T-cells to destroy the recipients blood component including the cancerous cells.
With blood cancer, relapse is a big deal. You need to get rid of all the cancerous cells. Simply relying on the chemo does not work well. Hence, autologous transplant is not an ideal therapy. You really need the graft vs. tumor effect. The donor blood cells, once grafted, will seek out and destroy the cancerous cells in Maya’s body.
And this is where the balancing act comes in.
- NK Cells cause GVHD. But, it’s the naive NK cells that are the culprit. Naive NK cells are those cells that have not been activated. That is, “called” to battle.
- So, NK cells are severly reduced from the transplant. Approximately 1/1000 th will make it to the host.
- In order to reduce GVHD, Total Limph Node irradiation (TLI) is performed as well. We don’t want the “nuclear bomb” to go off inside maya. Even with such reduction, GVHD can still occur. However, GVHD at St. Judes is in the 5% range, as opposed to 20 – 65% reported prior to these two adjustments.
- Since you reduce the NK population as well as have a limited number of T and B cells, you are open to infections. You are likely to get viral, bacterial and fungal infections. And until the stem cells graft, which typically takes 10 – 20 days or so, you are severely immune compromised.
- The “study” part of the treatment is that within these parameters, the doctors will add NK cells at some point to see if that has any positive affect.
Yes, the therapy is tough. And yes, there is mortality associated with the therapy. The big concern with Maya is that she’s been heavily treated. So, in this sense, it’s not certain how Maya will respond to the therapy. That’s part of the reason why St. Judes takes Maya’s overall condition under consideration. Dr. Triplett has turned down patients, because he did not feel that the therapy may benefit the patient. In other words, as difficult as it may be, he has turned down patients because he felt that the patient was strong enough to survive the therapy. Thanksfully, Maya is not in that category.
St. Judes also has a set of guidelines. For example, if the rate of Acute GVHD is greater than 10 %, St. Judes will shutdown the study. Also, if Non Relapse Mortality rate is greater than 15%, St Judes will also shut the study down. In other words, St. Judes Guideline is that if they are losing roughly 1/4 of the subjects, the study will be shutdown. The fact that the study is open and recruiting candidates, implies that the mortality rate is lower than 25%. So far, in this particular study, they’ve done well. There were 8 patients so far, and although not discussed in detail, it seemed that all of the patients have survived thus far.
Although this study is relatively new, the “back-bone” therapy has not changed in 10+ years. That is, the use of KIR mismatched, haplo transplant. Each new study has been a progressive refinement of the initial idea. So, while one can’t rely on the statistical measures here, the overall difference would not be significantly different.
Dr. Pai is a Radiation oncologist. In this study, part of the protocol is a Total Lymphoid Irradiation (TLI). It used to be that the protocol used to involve total body irradiation (TBI). However, TBI did not increase the overall survival (OS). Hence, TLI came about. The objective of the TLI is not to kill the cancer cells, but rather, to immune suppress the patient further. The suppression in turn will help with the grafting and subsequently with relapse. The overall numbers were impressive.
In terms of dealing with GVHD in the 50 – 65% range, now, Acute GVHD occurs in less than 5% of the patient. And overall side effect were all temporal and not burdensome, because the overall amount of radiation is significantly less.
With our consultations, I felt much better about heading into this therapy. Would I choose to walk through these gates, no. Will it be fraught with difficulties and challenges, absolutely. Is there a significant chance that Maya succumb to therapy? Yes. But… it really is the best option for us now.
- Will Maya develop GVHD? How will I deal with this potential outcome?
- Will Maya graft? If so, how long?
- How much discomfort will Maya have to endure?
- How much additional damage will we done to Maya?
- Will we all come home?
These are not easy questions to entertain. But, it is with hope we proceed.
Often, I will take a giant step back, insofar as I am capable of it, and take a look at ourselves as well as those around us. Yes the medical science is severly wanting. We are lead down a path that is so difficult to walk. Sadly, that will not change anytime soon.
What I do see is the “true color” of human nature. I see it from our neighbor who so kindly shovels our walkway or makes us dinner on the night that we returned from St. Judes. I see it from the teachers at Maya’s school. I see it from other (NB) parents, who always keeps an eye out for us. I see it from our colleagues at work.
But mostly, I see it in my little daughter’s eyes. She is the epitome of “Joi de vivre”. She celebrates life each and every moment of her day. Whether she lives another year, or another 80 years, I don’t think it matters as much as how she lives it. Her joy comes from her inner self. It really has so very little to do with us, the parents. If there is small credit that we might take as her parents, it is that we did not cover or smother her light.