We are still on the fence of making a diagnosis for what Keegan is facing. If you happened to do a web search when I first mentioned Macrophage Activation Syndrome (MAS), you would have found that it is virtually indistinguishable at presentation from Hemophagocytic Lymphohistiocytosis (HLH). In theory, MAS is a complication of juvenile rheumatic diseases (such as rheumatoid arthritis, vasculitis, etc), and HLH is a blood disorder that can be genetic, reactive (in response to an infection), or idiopathic (no known trigger). Both are, to put it in hugely simplified terms, conditions where the immune system goes completely nuts. The worst of both conditions results in what is called a "cytokine storm", where there is so much inflammation in your body, that it feels like the worst flu you have ever had....times about a million. Again, if you looked up cytokine storm when I first mentioned it, you probably would have seen that it was likely a cytokine storm that was the cause of death in otherwise healthy people after H1N1 exposure.
The criteria for diagnosis are the same; both cause raging inflammation in the body, decreased blood counts across the board (white, red, and platelets), coagulopathy, etc. But the treatment differs widely. MAS is treated with a variety of immunosuppressants, including high dose steroids and a drug called anakinra. Keegan has completed the three-day steroid pulse and been on anakinra for two days now. HLH, however, uses the same drugs, but also involves a round of chemotherapy and possibly bone marrow transplantation. People with underlying rheumatoid disorders can have recurrent MAS flares that are not fatal. Children with HLH rarely survive a relapse, prevention of which is the reason for transplantation.
While Keegan meets every one of the criteria for diagnosis of either or both, his medical history makes it more difficult for us to decide at first glance which one this is, and thus, what the next step should be. No one knows what either looks like under the umbrella of an immunosuppressive regimen after a heart transplant at 7 days of age. I mentioned a few days ago that the many doctors here working on Keegan's case where rethinking his many ups and downs over the last four years. It appears that what we thought were a strange combination of isolated incidents could have been recurring flares of MAS/HLH that were mediated by his heart transplant anti-rejection drugs. A few examples:
- Keegan has been cytopenic his entire life. This means he has never had enough of any type of blood cell (hemoglobin, white blood cells/neutrophils, and platelets). At times this has caused him to be dependent on blood transfusions, GCSF and epoetin injections, and platelets replacements.
- Two of his three liver biopsies showed evidence of hemophagocytosis.
- We thought he had a rare form of hemolytic uremic syndrome (HUS) induced by one of his transplant medications, tacrolimus. By reviewing some of the labs from that timeframe, it is possible that this may have actually been a MAS/HLH flare that we inadvertently stopped by switching him to a drug called Simulect. High IL-2 levels in your blood are a criterion for HLH, and Simulect is an IL-2 interceptor. This may explain why Keegan made such an unexpected recovery from HUS. We also gave Keegan five doses
- Most recently, Keegan's bone marrow biopsy results show signs of hemophagocytosis. He also has had some recent bleeds in his brain that may have been aggravated by the MAS/HLH.
Some of Keegan's labs have improved with the current course; some have not. His inflammation markers are slowly trending down. One level, ferritin, has normal values of 0-75. Levels over 10,000 are the cut-off for chemotherapy in general according to hematology's protocols. Keegan's levels peaked on Saturday at 48,000. His blood counts improved slightly with steroids and the blood transfusion, but they have already returned to their old levels. He is still bleeding, and his blood has not regained the ability to clot properly, despite three transfusions of fibrinogen and a blood transfusion. He is either asleep, completely agitated, or "zoned out". It's this last development that has been of most concern. Tomorrow, we may have to run an EEG of his brain activity in order to know for sure that he is not experiencing seizures of some kind or repeat his brain MRI to ensure the bleeds have not grown.
Tomorrow the entire team of doctors will meet again to discuss Keegan's case. This time, the oncologist specializing in HLH at the hospital will attend, as will the ICU attending. These "team meetings" are astonishing to me. This never happens at home. I think we knew last week that what we were dealing with was extremely serious when we walked into a room of 20 doctors with drawn faces telling us how sick Keegan was. And we hadn't even seen the worst of it yet. Yet, it's really hard to admit that your child is sick when they are on the regular cardiology floor, not intubated, not on dialysis. There is obviously no denying it now, but it still could be lightyears worse. And that is what everyone is scared of, right now. Because "lightyears worse" could happen tomorrow, two weeks from now, a year from now. And what will that look like? Will it be something Keegan can come back from the next time? What should we or can we do to prevent a "next time".... especially one that he can't fight.
The decisions we will have to make tomorrow and in the coming days are ones that no parent wants or should have to make. It is not nearly as clear cut as it was at first glance. No one wants to do too much too fast if it isn't necessary, but we have no crystal ball. There is no way to know what will happen, no matter which path we choose. It appears that no one thinks it is as much of an "if" as a "when", but how much are we willing to risk now if we don't know when the "when" will come. We are trying our hardest to gather as much information as we can and surround ourselves with as many people who are experts in their fields as possible. And right now, I think that's the only thing we can do. No one is going to be able to make this decision completely for us, and unfortunately, there are enough different ways of treating MAS and/or HLH that not all of the doctors will ever be in complete agreement. Anything we do will be taking a huge risk. I just pray that we choose the one with the biggest benefit because I can't afford to lose him. And I refuse to let him go through this ever again.
So once more, I will ask for your prayers not only for Keegan but also for me, Gray, and every doctor working tirelessly to help him. We have no doubt that he is in the best possible hands. Those of his doctors, his family, and every single pair of hands lifting him up in prayer to the Father. Thank you for helping us to help him on this road.
Risk more than others think is safe. Care more than others think is wise.
Dream more than others think is practical. Expect more than others think is possible.