Cincinnati review

I suppose it's time I wrote about our trip to Cincinnati Children's Hospital since we got home almost a month ago!  I have put it off for awhile because (1) things have been a bit crazy since then and (2) we didn't learn much that we didn't know before the appointment.  Frankly, I'm not sure where to start!  No place like the beginning, I guess.

We flew out on Tuesday, the 24th.  This was Audrey's first plane ride ever and only Keegan's second on a commercial flight.  I am not a big fan of airplanes, especially small ones.  We only purchased three tickets, taking Audrey as a "lap child" (which by the way, is my new favorite phrase...seriously, what is she? A chihuahua?).  We got more than a few sideways glances for pulling out the clorox wipes and going over everything in an arm's radius, not to mention for Keegan's mask.  Overall, the kids did great, and the day went pretty smoothly.

We stayed with a friend of mine from high school, Amy, and her amazing family in a suburb outside of Cincinnati.  Talk about making us feel welcome and easing a stressful situation.  Keegan and Addie (2 months apart) hadn't seen each other in over a year but were instant friends once again.  I think Addie had a difficult time understanding why Keegan wasn't talking to her much, but they had a great time anyway.  Matt and Amy's youngest, Jameson, is three months older than Audrey and a bone marrow transplant survivor.  It is helpful to have someone to talk to who has lived through what you are facing (bone marrow and solid organ are two vastly different transplants), but to have true friends who are honest and loving and really understand your fears and day-to-day life...priceless.  Absolutely priceless.  We stayed up way too late each night talking and sharing.  Maybe it is a blessing in disguise that we don't live closer to each other.  We may never get anything done otherwise!

Jameson and Keegan playing at the train table

Audrey in the castle

Audrey and Jameson playing.

This one is rehearsal dinner worthy. Heehee!

The simply amazing Jamo

Addie showing us her perfect dance moves

The typical attempt at a group shot.  

Audrey was a little less than enthusiastic. 

On Wednesday, January 25th, Keegan had his first appointment with the bone marrow transplant team at Cincinnati Children's.  The doctors had done a lot of research on Keegan's case before we made the trip.  They had ordered many different tests on blood we sent beforehand, including looking for known genetic mutations for HLH, had reviewed much of his medical records, and even reviewed the actual biopsy slides from his bone marrow and liver biopsies in Boston.  Everyone made us feel extremely welcome.  We felt the doctors were very thorough and available to answer questions.  Unfortunately, we left with about as many as when we came in.  Because as always, there is no clear answer when it comes to Keegan.

The 2004 published diagnostic criteria for HLH, hemophagocytic lymphohistiocytosis, require a finding of 5 of 8 known symptoms.  (Click here for a link to an article describing the criteria that was co-authored by one of the doctors we went to Cincinnati to meet, Dr. Fillopovich, if you are interested.)  Keegan has met up to 4 of them for most of his life, and by last summer, he met 6 of the 8.  (Click here to read the post I wrote while Keegan was in the CICU in Boston describing the differences between HLH and MAS, macrophage activation syndrome.)  So according to textbook definitions, he has HLH.  However, the doctors at Cinci, who are the world's leading experts in this rare disease, believe that one criteria (soluable interleukin-2) is the singularly most reliable indicator for a true diagnosis of HLH in the absence of a genetic mutation.  They do not believe that all the genetic mutations for HLH have been discovered at this time, but Keegan does not have any of the ones that they have identified.  He also has normal soluable IL-2 (a protein involved in the immune process) levels, even during "flares".  

Additionally, Keegan experienced a type of coagulopathy (inability of blood to clot) that the team had never seen before in their experience with HLH.  Keegan landed in the ICU in Boston mainly due to the inability of his actual bone to stop bleeding after a bone marrow biopsy and aspiration.  Biopsies and lumbar punctures are a routine part of HLH diagnoses, which was why it was so important that we obtain the biopsy before starting treatment with pulse steroids at the time.  Even with low platelet counts and low fibrinogen levels, there is no danger usually to doing these invasive procedures.  Keegan's platelet levels got fairly low (in the 30-40s), but his fibrinogen levels were actually not detectable and his d-Dimer was extremely, alarmingly high.  Obviously, I'm not going to explain all of that here, but suffice it to say, the doctors in Cincinnati had never seen anything like it before.  

Given all this, the team was reluctant to call what Keegan has HLH.  However, it doesn't quite make sense to call it MAS either, as he has no underlying rheumatologic disorder.  When it comes down to it, Keegan has some type of severe, life-threatening immune system dysregulation that looks an awful lot like HLH.  It could be as a result of heart transplant at birth (although there are no other known cases like his in what has become a not-so-unusual procedure) or something he was born with.  Not having a true diagnosis makes decisions regarding his treatment more difficult.  But honestly, it just puts us right back where we were before our appointment.  Knowing what the end result is (dangerous flares of an overactive immune system) but not why it is happening or what the best approach is to stop it.  

The ultimate cure would be a bone marrow transplant.  Audrey was tested the following day in Cincinnati, but she is not a marrow match for her brother.  Gray and I are not matches either, but there are a few possible unrelated matches in the national bone marrow registry.  For now though, the team does not want to proceed to transplant.  Without a known genetic mutation or abnormal IL-2 levels, they did not want to risk the damage to his heart and overall health by proceeding to transplant.  Keegan's heart transplant makes the decision process much more difficult.  Basically, we will have to continue to try available drug therapies until his immune system cannot be controlled anymore.  At which point, he would be in danger of going into antibody-mediated rejection of his heart and prevent him from receiving a bone marrow transplant at all.  

The only picture I got of the hospital.  Oops.

Waiting in clinic to see the doctors and get blood drawn

Audrey - the poster child for blood draws!

She did not even bat an eyelash the entire time.  What a trooper.

I know this is very confusing, and I apologize.  I think the doctors who are experts in this field are still confused about Keegan, so you can see how difficult it has been for me to put even some of it out here.  Ultimately, the "cure" is too dangerous for him right now.  Keegan is ironically too "controlled" (and doing ok) at the moment for transplant, and yet, by the time he is in need of one, he will likely be too sick for it.  We know we can keep him somewhat under control with large doses of corticosteroids, however they cannot be sustained for long.  We will continue to wean the steroids he is on now, and if he continues to flare as the steroids are reduced, more difficult decisions await.  We are trying some rheumatology drugs that work on interleukin-1 response (the anakinra he's on now, and the rilonacept that we will likely try next), which is a different part of the immune response.  When those stop working, we will likely have to resort to using chemotherapy over the long-term.  Not until then will we be able to reevaluate him for a bone marrow transplant.  By then, the antibody production in his body will likely have attacked his graft (his heart, a foreign organ in his body), making him too unstable for the intensive chemo preparation and grueling adjustment after bone marrow transplant. 

If you have hung on through this post with me, thank you.  What you have gleaned at this time (hopefully) is that we are essentially in a no-win situation with our precious Bug.  We have some of the world's most brilliant minds working to figure him out and helping us to make the best decisions we can for him.  In between those decisions, we are trying to treasure the everyday moments, as well as the extraordinary ones.  We are holding tight to memories made while he is feeling well and praying every single day that he has years upon years of those moments to come.  There are days where the weight of this knowledge bears down on us so unrelentingly that we simply want to give up.  We want to beg God to spare Keegan the rest of the journey because we have been warned of how difficult it will be.  But we wouldn't give up a single second of it.  We will continue to fight for him and look for answers.  For a cure.  For hope.  But we know where our hope comes from.  In Him, we have no reason to fear that the rest of this road will be too much for us to travel.  God will carry us the days we can't go on.  And He has surrounded us with family and friends to walk it with us.  We cannot thank you enough for that.

Return of TPN

I hope y'all can forgive me for taking a week off from updating.  This c.diff infection is wearing all of us out, especially Keegan.  He finally started to get glimpses of his old energy and happiness back yesterday, but it comes in waves.  We have been chasing his electrolyte levels like crazy with oral and IV supplementation.  He wants to eat, but it just goes right through him.  It will likely take a long time for the c.diff to correct itself.  (Quick education: clostridium difficile is a bacteria often found in hospitals that has a minor effect on healthy people but can overpopulate in the intestines after antibiotics have cleared out the "good" bacteria.)

Since we know Keegan is going from really bad diarrhea to his baseline diarrhea, his GI doctor and dietician felt that we should go ahead with using TPN three nights per week to maintain his electrolyte levels.  What we know now is that Keegan's intestinal problems are the effect of immune dysfunction.  His GI system is the first target of an over-production of antibodies (what we originally thought last summer was autoimmune enteropathy but now know to be part of a bigger picture of a systemic immune dysfunction that looks a heck of a whole lot like HLH).  As we wean the steroids as part of Keegan's immunosuppressive regimen, we will see his GI problems continue to worsen.  If he eats food and enjoys mealtimes with the rest of the family, he will have diarrhea.  If he is fed elemental formula through his g-tube, he will have diarrhea.  His GI doctors both here and in Boston were of the opinion that if eating makes him happy despite the tummy problems, let him!  We might as well support him now with TPN for electrolytes and adjust over time for calorie maintenance.  That is pretty hard to argue with.

Still, this was a torn decision for Gray and me.  In the grand scheme of things, it's minor.  We know he will feel better and be able to fight better when he is properly supported with nutrition.  Adding it back in now, however, is recognition that TPN will be a long-term part of our lives.  And that is a major add-on that is pretty difficult to accept.  Additionally, we have seen how miserable the extra fluid retention from steroid use has made him and how it raised his blood pressure even higher.  It's a delicate line to walk.

No matter how we feel about it, tonight the TPN returns.  It has been four and a half months of freedom from pumps.  We will run it for 10 hours three nights per week.  No pumps to drag around during the day.  No constant drips of formula through a g-tube pump that makes him lose interest in food.  Keegan's port is accessed all week anyway for twice a day IV infusions of anakinra, so the line is there to be used.  

This is a pretty big step in our long-term battle for Keegan's health.  We are surrendering a big piece of ground with this.  It makes me feel like this is just the beginning of the end of good or stable times for him.  And that breaks my heart.  Even if it is the right thing to do.

More of the same

Keegan does have c.diff.  Diarrhea to the n-th degree.

Audrey has been super-glued to my side for the last three days.  I'm sure the upheaval lately has her legitimately concerned we will leave her again.

Labs this morning looked mostly better.  Anemia worsening.  Not sure why yet.  Electrolytes are still awful.  Not unexpected considering the diarrhea, but it meant he had to have a second IV magnesium infusion for the week.  Considering the c.diff will likely take a long time to clear his system and that his baseline diarrhea has returned, we have an appointment next week with his GI doctor to discuss going back on TPN soon.  Hopefully, it will just be overnight a few days per week.

Audrey threw up in the car this morning.  Right as we got on the freeway to go downtown for labs.  Nothing like stopping the car on the side of the road to clean-up vomit when you are already running late and still have a 30 minute drive ahead.  So far, she has no other symptoms and is happy as long as she is doing what she wants to do.  Only time will tell if we are about to ride the virus-flare rollercoaster again.

Keegan is an emotional train wreck.  That should probably be italicized and bolded.  It could be for a plethora of reasons, but it is absolutely NO fun.  He is miserable and making the rest of us feel that way too.  Really ready to see my happy Bug again.

More of the same.  

Praying next week is where things start to turn around in this house.  I hope to get a post up about what we learned in Cinci soon.  Things have just been too crazy.  Thank you again for sticking by us.  It really makes all the difference.

Tuesday too

After a manic Monday, I could have used more terrific than terrible in my Tuesday.

If you have ever heard the words "c. diff", you probably know what I am talking about.  I knew something was wrong as I headed down the hallway (clue #1) to Keegan's room this morning, and when I opened the door, my fears were confirmed.

Needless to say, it was doomed to be a pretty miserable day from the get go.  A magnesium infusion didn't help that misery.  Hopefully it at least helped his dehydration and magnesium deficiency.  Add a possible UTI from little sister at the end of the day (which we think was probably a false alarm after a quick run to the pediatrician)....whew.

I would like a mulligan on this week so far, please.  Thank you.

By the way, how is it possible that this little ladybug turned 20 months old yesterday?

Crazy, right? 

(Don't ya just want to squeeze her?!  Seriously.)

Manic Monday

Another manic Monday trying to keep Keegan outpatient.

8:30am - Draw last amount of blood that Cincinnati ordered to be sent to a private lab in Canada for testing.  Assuming all the paperwork was ok and that we had done this several times, I ask my mom to drop it off at FedEx after she takes Audrey to school.

8:45am - Audrey off to school.  Clean Keegan up and throw some clothes on him after his first bad diaper of the day.  Head off to Children's downtown for labs.

9am - Stop at Dunkin Donuts drive through for an extra large coffee + expresso shot.  Somehow I knew it would be one of those days.  Get on the highway before I realize they put sugar in it.  Ahhh!  Completely undrinkable.  Now I'm starting to feel as drowsy as Keegan is.  He's already dozed back off in the back seat, after only being awake for about an hour.

 9:45am - At the hospital.  Get to clinic.  Get labs drawn.  Still waiting on a return call from rheumatology (which is down the street at Scottish Rite Hospital; 10 minutes from where I am now & 45 minutes from my house) for a post-hospitalization follow-up.  Get a call from my mom saying FedEx by her house wouldn't take a "clinical package"with "biological specimens" (despite the fact that I've sent two such packages from there already), so she is headed to downtown Plano to the main office to drop it off.

10:50am - Still no word from rheum, so I head home with Keegan.  My mom calls to say she finally got the blood shipped after filling out a second set of paperwork for out-of-country packages.

11:30am to 12:30pm- Arrive home as the phone rings.  Appointment with rheumatology at 1pm.  Have an hour before we have to head back downtown.  Keegan's second bad diaper of the day.  Unload the dishwasher, wash syringes; field phone calls from insurance and return emails.  Call my mom & ask her to pick Audrey up from school.  Keegan finally eats a small lunch...some of which he proceeds to throw up from the retching he's been doing for weeks now as we are about to run back out the door to Scottish Rite.

1pm - Wake Keegan up from his second nap when we get to Scottish Rite for clinic visit with rheumatology.  Spend most of the appointment with Keegan curled up in my lap.  Until he has another bad diaper.  Stand Keegan up.  While trying to wrap up our visit with the doctors, I see his diaper has leaked down his leg, onto his shoe and the floor.  Learn that most of Keegan's labs are starting to look better, but we need to slow down even more on the steroid wean.  Repeat labs on Friday.  Leave the hospital not only defeated by the new steroid wean plan but also the need to take Keegan out of the hospital in nothing but a diaper and tshirt.

3:15pm - Leaving Scottish Rite.  Get a call from the transplant team that Keegan's magnesium levels are much too low.  He needs an IV mag infusion.  Seeing that I need to get Keegan some clothes at home, it will probably be at the Legacy ER.

3:50pm - Get home again.  Change another bad diaper.  Get Keegan cleaned up, dressed, and start laundry.  Get a call from team that we can do the 4-hour infusion tomorrow at the Center for Cancer and Blood Disorders.

That only get us to 4pm, but unfortunately, now I need another glass of wine for recounting it all in writing....

Home

Things got a little busy yesterday, so I wasn't able to post that Keegan actually was allowed to go home in the afternoon.  His ferritin level was 4,000, which was a good improvement (still very, very high but coming down).  However, his blood counts all continued to drop, while some of his liver numbers worsened also.  The hope right now is that these levels are all just "peaking" at a rate slower than the inflammation markers and that they will normalize in a few more days.  The blood counts dropping is slightly confusing because steroids should cause them to be artificially high.  Steroids generally stimulate your bone marrow to kick everything out, even underdeveloped cells, making all your counts rise temporarily.

There wasn't much we could do about any of these things quite yet except for watch the levels, and we can do that from home.  We will recheck labs on Monday morning in clinic.  We can do transfusions or start him back on GCSF outpatient if need be by then.  For now, there were more risks to being inpatient and picking up a new infection than not drawing labs for one day at home.  We will finish the steroid burst today and return to 7mg of prednisone tomorrow.

Keegan is still very, very tired.  That is likely to continue for awhile longer.  His GI problems are worsening too, which is the opposite of what we've seen in the past on higher steroid doses.  Not sure what to make of any of it yet.  We will follow up with rheumatology at the beginning of the week.  We need to get him settled from this flare before we make any other decisions in regards to his treatment.  Since we weren't able to identify a viral trigger, we will probably need to resume the steroid wean and see if he continues to flare each time we get to a certain dose or not.

Thank you for all for each and every prayer said to help Keegan get home once again.  We are so grateful.  More tomorrow once we know it.

Steady

Keegan's holding steady with a little more improvement in his ferritin levels today (11,000).  The rest of his labs look the same.  We went ahead and switched to oral methylpred tonight at the same dose.  If he tolerates that over the weekend, his last "pulse" dose will be Sunday morning.  Then, he will get no steroids Sunday night.  If labs continue to look stable Monday morning, he will go home on 7mg (so essentially, 30mg to 15mg to 7mg over three days) and follow up with more labs in clinic next week.  That is a pretty fast steroid wean, so we are praying it goes well.  I anticipated we would switch back to prednisone with the switch to oral tonight, but they didn't.  We will have to ask tomorrow if he will stay on methylpred/solumedrol for good or just through the end of the pulse.

It's hard to say whether today was an improvement or not in the way Keegan actually feels.  He is still waking up around 7:30am and falling back asleep around 10:30am after the first steroid dose.  He did not eat breakfast or dinner but managed a bit more than just a piece of string cheese for lunch.  What did him in for the afternoon was an attempt to go to play therapy after lunch.  Keegan got very excited to go to "Ms. Kristin's playroom", but he only managed about 15-20 minutes of play before he asked to be carried back to his room.  Then, he proceeded to take his second nap until 5pm.  A brief visit from Audrey (our first since Sunday), and he was asking to go to sleep again by 7:15pm.  Remember that this is our boy who dropped his nap almost two years ago!

Anyway, no change in the plan for now.  We are praying for good rest tonight and better energy and attitude tomorrow.  We should have a phone conference with the doctor in Cincinnati on Monday to flush out what they are thinking based off of everything we have sent so far.  We also emailed our team in Boston to see if they had any advice; hoping to hear from them Monday too.  Thank you once again for supporting us on this journey.

"Teddy isn't feeing well.  Maybe I can help!  Dr. Audrey is on call!"

"Let's take your temperature!"  

(In your eyeball, of course.  Most accurate readings, obviously.)

"Uh oh, Teddy.  You have a fever.  I think this might be a flare!"

"Aww man, Teddy.  I know how that feels.  I'm so sorry!"

Watch

The switch to IV methylpred worked, and Keegan's ferritin dropped to 18,000.  The rest of his labs look roughly the same, but we'll take it.  The plan remains to stay on IV until we see a bit more improvement.  I am hoping that if his labs look better tomorrow, we can switch back to oral prednisone tomorrow evening.  Then, we will complete the 5-day pulse before weaning back to 7mg.  That is the place in the wean, almost a month ago, that we first started to see GI symptoms.  We will stay inpatient at a minimum through a day into the switch to oral to make sure he handles it ok.  Maybe a Sunday evening discharge.  Then we could follow labs closely in clinic through the step down in dosage.  His anakinra dosage will stay maxed out until we decide he is stable enough to go back to the standard dose.  More waiting & watching.

I was hoping that the drop in inflammation would help him feel better.  I was wrong.  He was asleep or fighting sleep most of the day.  Still extraordinarily crabby.  I poured him into a wagon this afternoon to take a trip outside before the rain comes and stop by the library for some more books.  He didn't want to do either of those things but allowed me to pull him around anyway.  Then, he wouldn't let me stop.  So, we walked at least half an hour around the cardiac and GI floors before he let me take him back to the room.  Then he just stayed in the wagon, not wanting to move, watching Nemo, for another hour before he let me put him back in bed.  He perked up a bit when Gray came back from work, asking Daddy to build him a tower of blocks.  Maybe I'm too boring for him!  It was short-lived though.  Gray managed to get him to eat almost two chicken nuggets and walk to the nurse's station to say "good night" before he was sound asleep again.

Hopefully tomorrow will be better.  We're praying so.

Then again, maybe he just needed to be held by an angel for awhile.

Always there for him, Miss Priss.

Switch

Keegan's bone marrow laughed in the face of oral steroids.  Ferritin rose to 26,000 today.  Lymphocytes are nonexistent, but the remainder of his labs, while all continuing to trend poorly, are not worsening at quite the rate we have seen in the past.  So tonight we are switching him to IV steroids.  We have dropped the "pulse" plan and are proceeding with the methlyprednisolone until further notice.  Until we see sustained improvement across the board.  Then, we will switch back to oral steroids (dose to be determined later) and will wait to ensure continued stability/improvement before we can go home.  The next step would be etoposide, a form of chemotherapy, if the IV steroids do not work.

Outwardly, he continues to look stable.  Very tired and increasingly crabby, paler than the bedsheets.  But stable.  Despite it all, he has managed to keep down a few bites of food here and there, so he's not even on a drip of any kind for once in his life.  His heart rate and blood pressure are lower than we are used to, but we aren't sure why.  The team is only doing one lab draw per day.  Gray and I would like to see at least twice per day of certain levels, but until we can write our own orders, we have to wait until tomorrow to see how things are going.  

We received a bit more information from Cincinnati Children's today.  Audrey, unfortunately, is not a bone marrow match for Keegan, nor myself or Gray.  There are, however, a few possible unrelated matches in the national marrow registry.  Again, we are not seeking a bone marrow transplant at this time, but we are doing the initial matching so that we know what our options are if we get to that point.

The team in Cincinnati also asked us to think seriously about transferring Keegan back up to there if he has not shown improvement by the weekend.  We are considering it, but at this point, they concur with the recommended course of treatment.  As of right now, Gray and I feel that if the treatment will be the same and if they are willing to continue to advise us from a distance, we need to be near our families.  The next few days will be crucial in making these decisions.  We need to see where Keegan leads us and see how the remaining labs we sent to them come back.  

The Lord is going to great lengths to teach me patience lately.  For tonight and the coming days, it continues to be "wait and see", "wait and see."  Thank you for joining us on the watch.