The big players; part 1 - Blood

When Tomas was born he had something called Transient Myeloproliferative Disorder (TMD for short). It occurs in around 2% of DS babies, and significantly less in the general population. It is very similar to a leukemia in that the bone marrow produces blasts (immature white blood cells) in much to high a ratio and crowds out any room for other healthy cells (red and white blood cells and platelets). His platelets were dangerously low throughout his first month and he recieved many a transfusion to try to stabilize that situation. Sometimes it worked and sometimes it didn't. Finally, that cell line recovered and he was able to come home. Soon afterward his RBCs started to decline and he needed 5 transfusions of red blood cells before he was 4 months old. But, also, finally that stabilized as the TMD began to fade away.

For many months after that he was simply monitored by an oncologist to make sure the TMD stayed away and to watch out for signs that it might transition to a true leukemia, something that still has a 1 in 3 chance of happening. To date, though, his bone marrow is as healthy as can be and is producing the perfect amount of cells and in their respective proper ratios.

However, during this monitoring phase one particular type of white blood cell kept coming up low. His neutrophil count was sometimes very low, sometimes a little low, but rarely normal. He was given the diagnosis of Chronic Benign Neutropenia and underwent various test to determine the cause. None was found. His marrow produces the right amount, they just don't get to stay around. Initially, everyone thought it was an autoimmune disorder - his body killing off his own cells - but no evidence of this has been found.

Chronic Begnin Neutropenia is a misnomer of epic proportions. The begnin part simply means it is not part of a malignancy - he is not neutropenic due to cancer. His oncologist in Texas put it perfectly, "It should be called Chronic pain-in-the-patooty Neutropenia." Having very few neutrophils to fight of bacteria leaves a body mighty susceptible to illness. And that is what happened, respiratory infection after respiratory infection; antibiotic after antibiotic from the time he was around 6 months old until he was around 2 1/2.
Most of his hositalizations during that time were from respiratory distress, they were normally pretty quick stays since we just needed to get him stabilized and had all sorts of meds and equipment at home.

What changed at 2 1/2? He had his first central line placed. A port in order to run fluids during his intestinal shut downs (another post). We were warned that the risk for infection with an internal device was significantly higher than without, add neutropenia on top of it and you were sailing in dangerous waters indeed. But we had not much of a choice. At 2 Tomas weighed 26 pounds, by 2 1/2 he weighed 20, we were literally watching him waste away. So we went forward.

The best explanation I heard of why the infection risk is so high is this: we all have bacteria floating around in our bloodstream in small amounts, the stuff is everywhere. Normally, our bodies defences (the primary one being neutrophils) kill it off. Day in and day out this little war goes on in your (incredibly amazing) body. Putting something foreign in the bloodstream (like a port, or a catheter, or whatever else) gives that bacteria something to cling to instead of the free floating it normally does. This gives it the opportunity to colonize and grow. Couple that with an insufficient neutrophil reponse and you get the nightmare we now live. Bloodstream infection after bloodstream infection. He has had a central line for a year now and has had 12 infections. Most of them have been contained to just the central line itself - the bacteria hadn't "broke free" into his circulating blood yet. A few of them have done just that, and those are the times we nearly lost him. Which brings me to March of this year.

After his 10th infection his oncologist sat me in her office and told me that he couldn't continue to fight like this. That his GI doctor was very concerned over the number of infections Tomas was getting and that he wanted her to do something about it. Her dilemma was this, the only treatment for neutropenia is an injection of a growth colony stimulating factor hormone (GCSF for short). This hormone has been linked to not only stimulating neutrophils but also blasts. The blasts from leukemia? Yup, the same. Some patients who had taken Neupogen (brand name for GCSF) had developed leukemia. She had no idea what his risk factor would be given that he already had TMD, and already had a 33% chance of transitioning. There was no literature on it, we were in uncharted waters.

Again, our choice wasn't too tough. Watching him fight and fight all those infections and late-night wondering if the next one was going to be the one he couldn't come back from propelled us forward. So in mid-March he had another bone marrow biopsy to establish a baseline and he started the injections. Because the doctor is so concerned and very cautious she began with one injection weekly. Typical children get one a day. For 4 months we tracked his neutrophil count and the effect the injections were having. It would boost his count to normal on injection day and for several days afterward. By day 4 his count was back below normal, and usually down far enough to be in the danger zone.

A few weeks ago, after the UTI scare, the doctor asked me how I thought it was working. I told her things were a bit better, he had only 2 infections in 4 months, where before he was averaging one every 4-6 weeks. But I felt like the dip he took after day 4 left him vulnerable and also left the question unanswered. Was the neutropenia the cause of the high rate of line infections? I felt like as long as he was still in periods of moderate to severe neutropenia we weren't eliminating that as a variable. She agreed, and we started twice weekly injections with the goal of keeping him over the moderate cut off number (ANC of 1000 in case anyone knows). There is no way an ANC of 1000 would leave you at risk for sepsis, so as long as he stays above 1000 even if he does get an infection, we will know it is not because of his neutropenia. After a 6 month tracking period we'll evaluate how many infections he's had and then go from there. He was already getting a bone marrow biopsy every 6 months to monitor the TMD risk and that will suffice to monitor for the GCSF as well.

Also, squarely in the blood body system department is Tomas' anemia. After those intial blood transfusions as an infant his red blood cell count had been completely stable. He did have a severe iron deficiency anemia when his nutritional status went to pot and he lost all that weight (a chronic GI bleed didn't help either), but iron supplements were sufficient treatment. Then in September of last year his RBC count and hemoglobin levels started to drop. At first everyone thought it was because TPN doesn't contain iron and since he was getting very little formula he was just iron deficient again. Not so, his iron panels came back just fine. As is par for the course with my little enigma, no one knows why he is anemic. he shouldn't be, but he is. At this point his diagnosis is Anemia of Chronic Disease. He requires a transfusion about every 3 months (fascinating tidbit is that blood transfusions only last an average of 3 months). His levels jump nicely after the trasfusion and just slowly slide downhill until the next one. As you can imagine this messes with his energy level in big ways. Near the end of a transfusion period physical therapy is simply torure for him, and he pretty much just wants to hang out in his crib or on one of our laps and watch tv. After the transfusion, we get Mr. pink lips and rosy cheeks with tons of energy; only to watch the slow fade until next time.

I would be grossly remiss if I did not take the time now to thank blood donors from the bottom of my heart. My son has had 8 blood transfusions and several doses of IVIG (also a blood product). They have kept him alive. They have given him the chance to fight the rest. Without the tranfusions there would be no need for anything else. Thank you for the opportunity to take on the world.