Clinical Update - 10 Days Post ATG

It has been ten days since Nathan's last ATG treatment. Unfortunately, his suppressed immune system has succumbed both to a minor cold and an overgrowth of e coli (not food borne, apparently e coli lives in most of our intestines but in some cases can move into our blood stream and cause a systemic infection) which may be further hampering any progress he could be making. Despite being isolated to his room for over a week now, Nathan continues to wear a constant smile. It definitely helps that he has received several packages and tasty food deliveries over the past several days which always boosts his spirits. So thank you again to everyone, you all know who you are, for bringing smiles to our faces in the midst of all this.

Progress?
We continue to wait for his bone marrow to respond to the treatment and specifically hope that his white blood and neutrophil counts begin to increase soon. That would be the first area where we would see progress and also his inability to fight infection is what is currently keeping us in the hospital vs. at the Ronald McDonald House. We will begin preparing for a bone marrow transplant if there aren't any early signs of progress within the next two weeks so we are both keeping our fingers crossed and preparing for the possibility of a transplant. While his blood counts continue to be stagnant at best, his liver inflammation is dramatically reduced which is a huge relief. It will take longer for his liver and spleen size to match the reduced inflammation but in time that will happen as well, it's just a long process. Today's lab numbers are below, again the blood counts are not indicative of anything given all the blood products and immunosupression he has had but I wanted to include them here anyway. Normal ranges are in parenthesis after each number for comparison. 

Blood Counts
WBC: 0.2  (4.0-12.0)

Neutrophil Count: 71 (1400-6600)

RBC: 3.58 (4.0-5.3)

Hemoglobin: 10.3 (11.5-14.5)
He received a RBC transfusion two days ago.

Platelets: 8 (150-450)

He is getting platelet transfusions every 1-2 days. Obviously he received a transfusion after this morning's count, his body continues to consume platelets quite rapidly. I can no longer keep count of the number of transfusions that he has received, maybe 40-something over the past eight weeks, and counting...

Liver Inflammation

AST: 277 (23-58)

ALT: 605 (6-35)

Total Bili: 4.0 (0-1.1)

Conjugated/Direct Bili: 0.7 (0-0.0.3) 

His bilirubin has shown a huge improvement over the past week. His skin and eyes are much more normal to reflect this near normal level of bilirubin so this is progress that we can literally see, which is so reassuring. While the above enzymes and bilirubin are signs of inflammation (aka hepatitis), his liver function continues to be normal despite all this prolonged inflammation. Seems that the possibility of a liver transplant, even though it was only slight, is far less likely now. It's a huge blessing to have one less thing to worry about although we are continuing to track his liver numbers quite closely since we aren't quite out of the woods yet, especially if he does need a bone marrow transplant. 

Medication Notes

We have finally solved the mystery of his strangely low prograf level. He was metabolizing a huge dose so quickly but then one day his metabolism slowed down, his level shot up and his dose was then reduced to a more normal level. I personally feel that his digestion was overstimulated due to his steroid dose and oral magnesium supplementation, resulting in very frequent stooling and an unhappy bottom. His tacrolimus (prograf) dose is down to a third of what it was and is now 5ml twice a day (10ml/day) where he seems to be holding a nice low therapeutic dose to help keep his T-cells from going out of control again. 

The last major change is a decrease in his steroids as they continue to wean him off over the next couple of weeks. He remains on GCFS/Neupogen at a double dose to try to stimulate his bone marrow to begin producing neutrophils. And of course he is on a course of antibiotics until his blood cultures show no signs of e coli for three consecutive days. All of his other medications are mostly treating any symptoms that he is encountering due to his illness or his medications such as his slightly elevated blood pressure and acid reflux. All in all, considering the severity of his illness, he is not as highly medicated as I would expect. 

Genetics
Our doctors feel like there is likely a genetic defect at the root of Nathan's illness. It seems that his body wasn't producing B cells or natural killer cells, essentially meaning he was unable to produce antibodies or mount an appropriate response to a virus, and this complete absence of these cells is highly unusual. There is no way of knowing if this has been the case his entire life and somehow he was managing it just fine in the past, or if this immune system imbalance was triggered by the same thing that caused his liver inflammation and bone marrow failure. So while we continue to wait for the HLH genetic testing (early next week) and NIH testing (mid-September) related to a possible GATA2 core immunodeficiency, the genetics team here is preparing to begin a full genome sequencing to attempt to identify any number of genetic defects that could be contributing to his current illness. Of course this will take up to three months to complete but the information could be vital to any future treatments that he receives.