Four Months Post ATG: Only a Tiny Improvement in Platelet Count and More Tests are Pending

Well, we are between months four and five post ATG at this point, but I held off on posting because I was hoping to have more information to share.

We have seen a very slight improvement in Ryan’s platelet count.  And by “improvement”, I mean that we have been able to space out the time between transfusions just a little bit.  He was requiring platelet transfusions each week, up until Halloween day, when we went to his clinic appointment expecting him to need a transfusion, but his platelet count was 32,000.  As a reminder, a normal platelet count for a child Ryan’s age should be 250,000-550,000.  Even though 32,000 is well below a normal range, doctors do not like to transfuse until a patient is around 10,000 in order to limit the number of transfusions they receive, which can increase antibodies in their system and, among other things, increase the risk of bone marrow transplant rejection and graft verses host disease (GVHD) if the patient later has a transplant.  Anything under 10,000 is considered in the “danger zone” where there is a high risk of hemorrhage.

So, we skipped a transfusion on Halloween and the doctor decided we could wait another week.  Within a few days, I started noticing petechiae (red dots that indicate low platelets) under Ryan’s Eyes and bruises on his arms and legs.  By the end of the 2-week period his platelet count was down to 6,000.

A week later, we finally were able to have our appointment with the doctors from Fred Hutchinson Cancer Research Center in Seattle.  The two doctors we met with specialize in, and research, bone marrow failure diseases.  I was a little bit disappointed because my expectation of the appointment was that the doctors had already received all of the tests Ryan previously had and that they would be making a recommendation regarding whether we should pursue a bone marrow transplant.  Instead, we were basically starting over with new doctors - answering questions, giving family history, etc.

They told us they wanted to do several more genetic tests and a new bone marrow biopsy.  They also asked our permission to map Ryan’s genome, which I think is really cool and I am curious to know if any new information comes out of that (although we were told that sometimes they get information that they don’t know what to do with).  One of the reasons for all of the genetic testing is that, if they do find something genetic, and Ryan does proceed to transplant, it could help the transplant team determine the pre-conditioning regimen.  Certain chemotherapy drugs can be more toxic if you have certain genetic conditions.

The doctors were great to speak with; it just wasn't what I expected the appointment to be all about. The lesson learned for me is to ask more questions in advance about what to expect. I had created an entire page full of questions about the transplant process, but that just isn't at all why we were there.  At the end of the 5-hour appointment, they took about 10 vials of blood for various tests and scheduled a bone marrow biopsy for November 21^st (tomorrow at this point).  Ryan’s platelet count that day was 25,000 so we were able to skip another platelet transfusion.

I tend to report a lot on Ryan’s platelet count, and that is because platelets are basically the first thing to go.  They only have a lifespan of about 6 days, where red blood cells can last about 35 days.  That is why platelet counts can go up and down so quickly.  I should mention though, that there has also not been much improvement in Ryan's white and red cell counts.  Ryan is still requiring red cell transfusions about every 3 weeks.  White cells cannot be transfused and his remain below normal.  One of the other numbers I pay attention to is his neutrophil count.  Neutrophils are a type of white blood cell that fights off infection.  The normal range for Ryan should be 1,500-8,500.  He had a few weeks where his went over 1,000 but they keep dipping back down.  He has been running in the 700-800 range lately.

Ryan ended up not getting platelets last week like we thought he would, however, by the weekend, it started to show.  He had invitations to birthday parties on both Saturday and Sunday, and I decided not to tell him about either one.  I knew he would want to go, but I was worried that he would get hurt or pick up germs at the events, which could easily lead to a trip to the ER.  One party was at Chuck E Cheese and the other was at a Little Gym.  I felt bad that he had to miss out, but I decided not to risk it.

Then, Saturday, he accidentally whacked himself with a lightweight bamboo back scratcher and it gave him a black eye.  This was followed by two other minor bumps while playing that resulted in bruises on his forehead.  The level of impact from these “accidents” to a person with a normal platelet count probably would have either left a slight red mark for a few minutes, or no mark at all.  But, when they happen to a Ryan, with low platelets, they result in him looking a little beat up.  Here is a picture of his eye:

What’s next?  

Tomorrow Ryan will have a new bone marrow biopsy.  The only other bone marrow biopsy he had was when he was admitted to the hospital at the time of diagnosis (June 24, 2013).  They will be looking for any signs of improvement and also any signs of other concerning items in his remaining cells such as PNH clones, MDS, or Leukemia.

One of the main things they look at in a biopsy is “bone marrow cellularity”. Cellularity is basically the percentage of bone marrow that contains healthy cells as opposed to adipose tissue.  At birth, cellularity is approximately 100 percent and then declines with time as people age.  Cellularity in a healthy adult is approximately 50%.  Cellularity in a healthy 4-year old should be around 70%-80%.  Ryan’s cellularity in June was less than 5%.  Here is what the bone marrow of a person with Aplastic Anemia looks like in comparison to healthy bone marrow:

Bone Marrow of an Aplastic Anemia Patient:

Healthy Bone Marrow:

After the biopsy, we will continue our regular weekly clinic visits and then have a consultation on December 9^th with the Seattle Cancer Care Alliance Transplant Team.  This is the appointment where we will hear about Ryan’s test results, options for bone marrow transplant, discuss all of the risks, worst case scenarios, etc.  We will get the results of the “World Book” search (international bone marrow donor search) and find out if Ryan has a potential donor.  We will also meet with a financial counselor (because, as you can imagine, it is expensive and there is quite a bit out of pocket that is not covered by insurance) and, last, we will tour the facility.

Please continue to keep us in your thoughts and prayers.  Although this journey has already felt very long, I fear that it is only really just beginning.

We celebrated a birthday this past week!

We threw caution to the wind and allowed Ryan to celebrate his birthday at, of all places, a bouncy place, where there were plenty of opportunities for him to bump heads with other kids, potential germs all over the place, and 30 foot inflatable slides sure to generate friction burns.

He survived.  And, he got to be a normal kid for a day.

Happy Birthday Buddy!

Three Months Post ATG: Still No Major Signs of Improvement

We seem to have settled into a pattern over the last month.  Ryan receives platelets each week and then by the following week’s appointment his platelet count is back down around 10,000.  He is also continuing to require red blood about every 2-3 weeks and his bruising is increasing to a similar level as to when he was first diagnosed.

My gut is telling me that we are headed toward a bone marrow transplant.  However, I am not the expert.  Speaking of which, we are still waiting to speak with the expert.  We started the referral process about 6 weeks ago and somehow, everything has not yet aligned to where we are even allowed to make an appointment.  I have confirmed that the referral has been received, but for some unknown reason, we are still not able to schedule.  I am beyond frustrated with this process.

Below are updated charts showing Ryan’s counts at 3-months Post ATG.

Save a Life. Why Would You Not?

Saturday September 14^th, I attended a fundraiser hosted by Julian’s Dinosaur Guild (http://www.juliansguild.org/julian/home.html).  The guild was started in honor of Julian Blackwell, who was diagnosed with Aplastic Anemia at the age of 3, in 2010, and underwent a bone marrow transplant in 2011.

The event was emceed by Keith Eldridge of Seattle’s KOMO 4 News, and donations raised help fund Dr. Akiko Shimamura’s research of bone marrow failure diseases at the Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital.

Dr. Shimamura is a leading expert in Aplastic Anemia and spoke at the event about some exciting work being done in her lab right now.  One particular study has identified gene markers that can help predict up to 10% of patients who will likely not respond to ATG treatment.  I imagine that, in the future, this may help develop a routine screening protocol that can spare “non-responders” from a harsh round of ATG treatment, and perhaps direct earlier efforts toward bone marrow transplantation or participation in clinical trials.

At the event, I had the opportunity to introduce myself to Dr. Shimamura and chat with her briefly about Ryan.  She reassured me that there is still time for the ATG to work, but that she would be happy to see him at her clinic for a consultation.

Last week, Ryan’s doctor determined that we are at the point where he recommends a consultation with Dr. Shimamura.  Since we are not quite to the “3-month post-ATG” benchmark when initial evaluation normally occurs, I simply asked the doctor if he wished that he were seeing more improvement in Ryan’s counts at 2 ½ months in.  He said that he has had some patients who were “late responders”, so he is still hopeful, but that he would like to have seen Ryan not so dependent on transfusions by now.  I asked him if another bone marrow biopsy would be scheduled soon to see how things are looking. Unfortunately, he said that it didn't make sense to do one right now, because without much cell growth (i.e. increases in counts), he expects that Ryan’s biopsy would look the same as it did in June.  Enough said.  With that, our conversation shifted back to setting up the referral to Dr. Shimamura, transferring bone marrow biopsy slides to her, etc.

Back to the fundraiser for Julian’s Dinosaur Guild…   The event also paid tribute to Julian’s two year bone marrow “transplantversary”!  It was encouraging to see Julian running around full of energy and hear that there were other bone marrow failure survivor’s in the room, including another child who has successfully been treated to remission with ATG.  However, the most touching moment in the evening came when the audience was introduced to Andrew, Julian’s bone marrow donor.

Two years earlier, Andrew had been in the middle of planning his wedding when he received the call asking him if he would be willing to donate.  Just days prior to the fundraiser, Julian and Andrew met in person for the first time.  Onstage, Julian’s family presented Andrew with a framed photo of them both together, with messages of thanks filling the matting around the image.  In that moment, Keith Eldridge asked Andrew why he had made the decision to donate.  An emotional Andrew put his hand on Julian’s shoulder, then looked up at the audience and simply asked “Why would you not?”

Would you be willing to save a life? Did you know that you can easily register online as a potential bone marrow donor?  A kit will be sent to you and you simply swab your cheek and return it – no initial blood draw is needed.  Chances are, you will never be contacted and have to decide.  However, even with over 9.5 million people already in the registry, some people requiring a bone marrow transplant will only have one match (or no match at all).  What if you are the one in 9.5 million match needed to save a life?  Would you donate? Why would you not?

To register, visit www.bethematch.org  Please, don’t just think about it as something nice you might do someday.  Take a few minutes right now to sign up online.  There might already be a patient out there that may not have a “someday” without the few minutes it takes you to register today.

Two Months Post ATG: Do we have a Partial Response to Treatment? Maybe… or Maybe Not…

Years ago, when I was a 20-something bachelorette, I was microwaving a frozen burrito when I received a phone call that would take my breath away and leave me feeling dazed and sick to my stomach.  It was the feeling of getting really bad news, and it was the first time I had ever received this type of bad news.  A friend had been killed in a car accident overnight.

I remember dropping the burrito, plate and all, into the garbage and then wandering aimlessly around the house in the hours that followed, until I finally crawled into bed and spent a restless night trying to sleep, but then continually waking to thoughts of this person and the tragic events.

Throughout the years, I have experienced this same “bad news” feeling at times.  I have felt it when learning of the death of my grandparents, the death of my uncle, the cancer diagnoses’ of friends, layoffs at work, the death of a coworker last year, and of course Ryan's diagnosis of Aplastic Anemia.  I think this feeling might be related to the temporary “fight or flight” response our bodies have to danger (or a bad situation).  However, I have been having this feeling on a regular basis lately.

For the first two months after Ryan’s diagnosis, an adrenaline rush of sorts kicked in.  The first month, I was on a mission to understand as much as I could about his condition and prognosis.  I read everything I could find on the internet about Aplastic Anemia.  I read websites, blogs, medical journals, information on clinical trials, researched hospitals throughout the country, researched doctors, and watched pre-recorded webinars.  The list goes on…

I also conducted many fruitless searches on anything that I could think may have been a potential cause of his condition.  My theories ranged from it being something in his sandbox, off-gassing from the building material in the new home we moved into when he was 9 months old, the Zantac his doctor prescribed him for acid reflux when he was an infant, something from a plant outside that he may have put in his mouth, something he was exposed to at daycare, or something I was exposed to when I was pregnant.  I was looking for something to help me make sense of it.  I now realize it will never make sense to me.

The second month, I read every book that was a patient’s story on Amazon:

Anatomy of a Miracle: Drew’s Story by Jennifer M. D’auteuil

Drew had an unsuccessful round of ATG and then received a Bone Marrow Transplant from a non-related donor.  He has had complications along the way, including a near-fatal lung infection, but is doing well today.

Danielle’s Story: A Daughter’s Battle with Aplastic Anemia by Shawn Williams

A heartbreaking story about 11-year old Danielle’s battle with Aplastic Anemia and her death due to complications of the disease.

Out of Nowhere by Esther M.R. Hougham

Esther recovered from Aplastic Anemia as a result of a sibling matched bone marrow transplant.

Blood Counts: My Triumphant Battle over Aplastic Anemia by Asa J. McMahon

Asa recovered from Aplastic Anemia as a result of a sibling matched bone marrow transplant.

I have since been in contact with Jennifer M. D’auteuil , the author of Anatomy of a Miracle: Drew’s Story, and have joined her Facebook page “BAND OF MOTHERS in the fight against Aplastic Anemia”.  I have enjoyed Jennifer’s positive attitude and find that she is a daily cheerleader of sorts for AA patients and their families.  I encourage you to buy her book and check out her Facebook page.

I have also continued to follow the blogs of several AA patients, including a blog about Nora Getchell, a young girl in New York.  I found the blog, written by her mother, the night Ryan started his ATG treatment in the hospital.

Nora is in her third year battling AA.  She initially received, ATG.  It looked like she was responding for a while, but then her counts fell off again.  She then received a bone marrow transplant last year, again things were looking good for a while, but in recent months the transplant failed.  The donor provided additional stem cells and Nora was given a “boost” last month.  She is still in the hospital, has developed several near fatal infections, and the graft of additional stem cells has officially failed.  They are now trying to manage infections and coordinate a second bone marrow transplant, from a new donor, to occur within the next 2-6 weeks.  My thoughts and prayers go out to Nora and her family.

While it is hard for me to read at times, Nora’s blog has given me a realistic idea of what a rollercoaster rider this disease can be.  Here is a link to Nora’s blog if you would like to follow her journey: http://norasstars.wordpress.com/

During Ryan’s second month post-ATG, I also analyzed every aspect of his lab results from every blood draw on record.  I created spreadsheets to track every result and corresponding graphs to look for trends and potential improvements in his counts.  I combed through stories of other patients who had ATG and, where numbers were mentioned, I compared them to Ryan’s for any potential clues regarding his progress.

My theory so far is that he is having a slight “transfusion dependent partial response”. That isn't great.  His neutrophil count has made some progress and seems to be hovering around 700 (still about half of normal).  He has also had a few spikes in his platelet count, which seem to be followed by his T cells aggressively attacking them at a rate of around 11,000 for the first few days, and then leveling off at a “burn rate” of 3500 a day.  When he was first diagnosed, he seemed to be burning through about 3500 a day, so this is where I get concerned that we haven’t made much progress.  While it is encouraging to see the spikes in his counts at times, it is just as discouraging that his T cells seem to kick into overdrive once they realize his counts have gone up (rogue T Cells are our enemy and are the attackers of Ryan’s healthy cells).  I have included updated charts of Ryan’s counts below.

Now we are entering the third month post-ATG.  Upon completion of this month, we will have a good idea of whether Ryan is responding to treatment.  I have completed my research, I have read the books, I have analyzed the data. We have an appointment Monday and Ryan’s blood will be drawn to HLA tissue type match him for a potential bone marrow transplant.  Unless his counts drastically improve this month, it is likely the doctors will ask us to start considering a transplant, and they will start looking for a potential donor.

In the meantime, I am to the point where I feel like there isn't much I can do to help.  I can pray that there is a perfect match donor out there if Ryan needs one.  I can make sure Ryan has his medication twice a day.  I can monitor his temperature for potential infections.  I can keep him away from large public gatherings. I can try to help him deal with the anger his medication seems to be giving him.  I can pray for a miracle. I can also love him more than he will ever understand.  Other than that, I am left to deal with my constant “bad feeling” and look for positive ways to channel my nervous energy and deal with all of this.

The Ups and Downs while we “Wait and See”

Brad captured this great picture of Ryan at Lake Sawyer yesterday.

The last two weeks have been a series of ups and downs.  Twice, Ryan’s platelets registered over 40,000!  This was so exciting!!!  Until… his numbers took a nose dive to 14,000 at each of the appointments that followed.  However, we did get to skip platelet transfusions at each of the appointments where it was at 40,000. This means he may be trending toward platelets once a week instead of twice a week.

Last Thursday was the last 40,000 count, and Ryan got to skip a platelet transfusion (although he did get another red blood transfusion).  I expected at today’s appointment that his counts would follow the same trend as the last two weeks and be at 14,000.  Unfortunately, they were at 12,000.  I know it is only a difference of 2,000 but any little thing that feels like a setback is increasing my anxiety level these days.  The count is also only 4,000 higher than when he was initially diagnosed at 8,000 at the end of June.

I am starting to get impatient and I wish we were seeing better progress.  I know that this treatment can be very slow to “kick in”.  We really have to wait until about three months post ATG treatment to get an idea of whether it is working to put him into remission.  (Three months will be mid October for those who are counting.  Just in time for Ryan’s 5^th birthday.)

Note: I have included graphs showing the trend of Ryan’s labs below.  I will try to include updated graphs about once a month.

It is so frustrating not being able to do anything but be patient and “wait and see”.  It is in my nature to want to hurry up and find something to fix this, but no matter how many hours I spend reading, researching online, quizzing the doctors, and analyzing the medical histories of other AA patients with blogs, I have to resign myself to the fact that I am probably not going to be the one who stumbles upon the cure for this dreadful disease while searching the internet or watching reruns of House.  I truly just have to be patient and take things a few days at a time.

We were finally able to get Ryan out of the house this weekend for a short hike.  He has been too fatigued this summer to do much, other than be a couch potato, do art projects, or have a few brief visits to school.  His doctor has decided to increase his threshold for red blood transfusions so that he doesn't get as exhausted and have other side effects in between transfusions (anger, loss of appetite, stomach pain, and mental changes).  This has really helped and, for the most part, he was full of energy this weekend.

We did a short hike down to Lake Sawyer and then walked the shoreline for about an hour or so before Ryan announced that he was tired and wanted to go back.  On the way back, as Murphy’s Law would have it, Ryan tripped and fell hard on his left knee.  He started crying and blood started trickling down his knee.  Within a few minutes, a large purple “goose egg” formed.  Luckily, the blood was from some surface scratches.  I could see it was watery from low platelets, but at least it wasn't gushing.  Ryan was a trooper and limped back to the car, where I cleaned and bandaged his knee.

I wonder if his knee injury could have burned up those 2000 platelets that I was expecting to have included in his count today…?  Last week, the doctor explained that platelets can get “burned up” doing their job, so I guess it is possible.  We will have to wait and see what next week’s counts look like…

What a difference a unit of blood can make!

This past week has been a little rough.  Ryan started last Thursday off in a super cranky mood.  He didn’t want to eat anything, was mad about every little thing, and just wasn’t acting normal.

He had an appointment Thursday morning, but his normal doctor was on vacation and we saw a doctor we had not met before.  When the nurse first took his temperature it registered at 101.2.  We had learned from Ryan’s regular doctor that a temperature of 101 in an immune suppressed individual should be treated “as if the fire alarm is going off.”  If he gets a fever of 101 we have to take him to the ER right away for IV antibiotics.

The nurse asked if I had brought an overnight bag.  I didn’t realize I should be carrying one in the car, but based on the fact Ryan has had two hospital stays within a month, it might not be a bad idea.  They waited and took his temperature again about a half hour later and it had gone down to 99.8.  Since his temperature dropped below the admission threshold, we were told just to monitor it and the conversation shifted to his labs.

The last two weeks in a row, his numbers had gone up slightly, so I was hopeful to see an upward trend.  However, at Thursday’s appointment all of the counts were down again.  I expected we would be sent upstairs for both platelet and red blood transfusions.  However, they only sent us for platelets and said he would probably need both platelets and red blood on Monday.  Note: We have been averaging 2-3 appointments a week, and not a single appointment has gone by where he hasn’t needed platelets.  He has been averaging red cell transfusions every couple of weeks.

My gut instinct told me that he should have had a red cell transfusion on Thursday or Friday, but I also know that they try to limit the red cell transfusions as much as possible for two reasons:

1)    If you have several red cell transfusions, your body can get overloaded with iron.  I have read this can start to happen at around 20 transfusions (Ryan has had about 5).

2)    The more transfusions you have, the more likely your body will reject a bone marrow transplant in the future (which Ryan may need).

So, Ryan got his platelets on Thursday and he headed into the weekend low on red blood cells.  I think that was a bad call.  Our little guy seemed to disappear for the weekend and was replaced by a psychotic grumpy old man in a 4-year old’s body.

Every single comment we would make to him was met with rage and the angriest glare I have ever seen on a child’s face.  For most of Friday and Saturday, he didn’t leave the couch.  He didn’t even want to sit at the table and play with Play Doh or color, which in my opinion doesn’t take much effort and he normally enjoys those activities.  Worst of all, he didn’t want to eat or drink fluids.  A few times, he would express an interest in food, I would make it, and then he would take one bite and leave the table.

By mid-day Saturday, he started going up to his room for hours at a time and putting himself to bed.  This is the same kid that normally fights going to bed at night, is up at the crack of dawn, and refuses to take naps. It is not at all like him to voluntarily take a nap.

Ryan slept most of the day Sunday.  When he would come downstairs, the littlest thing would set him off in anger and he would either curl up in a ball on the couch, or he would go up to his room in tears and sleep for a few more hours.

All weekend, I suspected he was in need of red blood, but I also thought some of the behavior could be due to side effects from his medication.  I wondered if his blood count could be so low that his brain wasn’t getting enough oxygen. I tried to do more research on the side effects of his medication (Tacrolimus / Prograf) and was only able to find a small study on the effects in children who had received kidney transplants.  There were a few kids in that study that had some psychological changes.

I put Ryan to bed Sunday night and was anxiously waiting for his appointment Monday morning.  I went to bed myself, but Brad woke me up a couple hours later to let me know that Ryan was crying and screaming inconsolably and he couldn’t figure out why.  We both sat with Ryan and tried to console him and figure out what was wrong.  I tried to rub his back and he would just angrily push me away.  He didn’t want to be touched.  Do you hurt somewhere? Does your tummy hurt? Do your legs hurt? Do you feel sick? Do you think you need to see the doctor? Does your head hurt?  All of this was met with inconsolable loud crying; a scary “I’m in excruciating pain” kind of cry.  I even asked if he could see because I thought maybe he woke up blind and it was scaring him.  I was just about to pack him into the car and take him to the ER, when I noticed he was kind of tugging at the pajama shorts he was wearing.  I asked him if his jammies were bothering him and he finally screamed “I’M COLD!!!”  Even though it was a warm night, he agreed to let me change him into winter fleece jammies (or “hot jammies” as he normally likes to call them), we put him into bed with us and then he slept peacefully through the rest of the night.

At yesterday’s appointment, his hemoglobin was 6.0.  Hemoglobin is the portion of red blood that provides the ability to carry oxygen throughout the body. A Normal hemoglobin is 11.5-13.5, so Ryan’s was about half of what it should be.  I don’t know if this means that his organs were only getting about half the oxygen they should, but based on his mental state over the weekend it wouldn’t surprise me if he at least had a significant decrease in oxygen flowing throughout his body.

After his appointment with the doctor yesterday, I came home to do some work (yes, I am still trying to work full time through all of this craziness – I don’t really have a choice) and Ryan stayed with Grandma N to receive both platelets and red blood.  Grandma N said he slept in the car most of the way home. He still seemed a little cranky when he got home and I started to worry that the transfusion hadn’t been the solution.  However, by 7:00 in the evening, it’s like a switch of energy was turned on.  He started running around the house, dancing, acting goofy; I even think I heard some singing at one point.  We had our little boy back!  What a difference a unit of blood can make!