Evan MacNeil's Personal Profile
April 2008: ATG fails to sustain Evan's counts; unrelated 9-of-10-matched donor identified
By February of 2008, Evan became transfusion independent and for a brief while, we enjoyed weekly clinic visits during which we celebrated rising counts. Transfusions were a thing of the past and we cautiously celebrated when his platelet count went from 18 to 25 to 30 to 31. It was a good month as his hemoglobin had risen to over 100 and he was holding onto an ANC of 1.1. We thought we were on our way to remission. As much as we rejoiced over that platelet count of 31, our dreams were shattered as we watched the count go just as quickly back down to 21 and 18 and then 11.... It was time for frequent red blood cell and platelet transfusions again.
Evan had enjoyed being back in school for only a brief time when, at March break, we realized that Evan was no longer safe from bleeding or infection and made the decision that his grade 5 year was done. It was an easy decision for us to make because we knew we had bigger issues to deal with and school would always be there when Evan was healthy again. The month of March was bad and reassured us that returning to home schooling was the best decision we could have made. Evan became more dependent on transfusions than ever before. Between red cell transfusions, Evan's hemoglobin would crash as low as 58. Between the beginning of March and mid-April, Evan had three separate three-day admissions for neutropenic fever and the reality of the situation was staring us down. At Evan's first clinic visit after his last discharge from hospital, we expressed grave concern for Evan and indicated that we felt it was time for an intervention of some sort.
The ATG treatment was deemed a failure and we were given the choice of doing ATG again, only rabbit this time, or BMT if a suitable donor could be found. We already knew, through hours upon hours of research, that outcomes were better with a well matched BMT than they were with repeating a treatment that didn't work in the first place. It wasn't long after that we learned the date for the appointment to discuss BMT options with the BMT team at Toronto's world renowned Hospital for Sick Children. April 16, 2008 would bring another dose of the scary reality that was our lives.
The decision to repeat the ATG or go to transplant (if a donor was available) was left to us. We already knew, through our researching and networking, that a BMT was the route we needed to take. We believed that we would be wasting precious time repeating the ATG treatment which didn't work in the first place. We were doubting that Evan's AA was auto-immune driven and began wondering if he suffered from short telomeres, a concept that, after reading a hundred times over, I could barely wrap my head around. What I was able to easily conclude from my reading was that not all AA cases are caused by immune system dysregulation and therefore not all AA cases can be treated successfully by immunosuppressive therapy. The longer we waited and the more treatments we tried that were unsuccessful, the more transfusions Evan would require and the more likely his low ANC would welcome a potentially fatal fungal infection, not to mention the risk of platelet refractoriness and fatal brain bleed.
We had our meeting with the BMT team at Toronto's Hospital for Sick Children in April 2008. It was then that we learned of Evan's three choices of donors. There were two cord blood units, both of which were 9/10 for HLA matching, and one adult donor who was also a 9/10 for HLA matching. The pros and cons for each stem cell source were explained to us, as well as the grim realities of a bone marrow transplant gone wrong, which happens despite everyone's best efforts. The doctor was so gentle with his explanations and there were certain words that he purposely didn't speak - he didn't have to. The odds would be in Evan's favour given his age and relative newness of diagnosis with not too many transfusions under his belt. There were no pre-existing fungal infections, and while Evan's ferritin level was well above 1500, he was not exhibiting any signs of iron overload. But, as well, there would be no guarantees of a successful outcome. If Evan were to survive the weeks post transplant when he would be without an immune system and white blood cells, the likelihood that he would develop a serious non-fatal complication, whether it be graft versus host or serious infection, was a given. We were warned that Evan would, for the first time since diagnosis, actually feel sick and look sick, very sick, but that we would have to "get through the bad to get to the good".
We left that meeting with such a variety of emotions. We were scared, we were so angry that our son would have to endure such a thing, but we were thankful and optimistic. We knew in our hearts it was the right thing to do and we believed our son would be cured. The decision for stem cell source was also left up to us with the encouragement to be back in touch with the BMT unit with our choice as soon as possible. We readily chose the unrelated living donor for several reasons: First of all, the mismatch was on the allele of DQB1, which is an area of very little importance compared to the mismatches of the cord blood units on the antigen of A, which could greatly increase the risk of graft versus host. Secondly, with a live donor, we had the potential to request more cells in the future if necessary. With all of this in mind, we emailed Evan's doctor the following morning with our decision. The ball was officially rolling.
Once the donor was notified, it took only about five weeks to learn that he was ready, willing and able to make the donation. We did know he was male, 31 years of age and living somewhere in the United States. We didn't know much but we loved him all the same.
In the weeks before transplant, email discussions took place between Evan's doctor and me, finalizing decisions on the conditioning that would be used to prepare Evan for BMT. Once again, we were given the decision as to whether or not to include radiation with the chemotherapies. Evan's doctor stated he was "sitting on the fence" regarding the need for radiation given the fact that we were going to be using four doses of cyclophosphamide and three doses of rabbit ATG which would be more than adequate to wipe out Evan's immune and blood making system. After doing some reading, we came to the conclusion that we would not use radiation but rather would speak to the doctor about adding fludarabine to the conditioning as an extra ounce of good measure, in place of the radiation. The doctor felt this was a reasonable idea so four doses of fludarabine were added to the regimen. With that, the stage was set.