BMT Day +7

We are officially one week post Nathan's BMT. This means that we are done with all chemotherapy medications and just waiting for engraftment to occur. For a bone marrow transplant patient, so much is measured from day zero. Days prior to transplant at "negative" numbered days and days post transplant are "positive" numbered days. I imagine for a good portion of his childhood, we will be counting the days, months and years post transplant as much as his own birthday. The significance of "Day 0" is tremendous to the point that I cannot possibly list all the reasons here but suffice it to say that his transplant will have lasting effects through the course of his life. 

I know lots of other families dealing with bone marrow transplant for aplastic anemia scour the web much like I did in order to kind of know what to expect. I also know that the circumstances are so individual and variable and also depend largely on the conditioning method used. Nathan's conditioning "roadmap" included several chemotherapy medications prior to transplant to clear out his own system and prepare for the new cells, as well as a few very small doses of different chemotherapy meds post transplant to try to reduce the risk of GVHD (graft vs. host disease) and common viral infections like EBV (Epstein Barr Virus). Here is his roadmap in detail, this only includes the major medications used in his conditioning and not the other medications used to mediate side effects or other issues he is having aside from the transplant.

• Days -6, -5, -4, -3: Chemotherapy Pre-Conditioning with Fludarabine, R-ATG and Cyclophosphamide/Cytoxan along with Mesna to protect his bladder from the Cytoxan and Tacrolimus (similar to Cyclosporine) for continued immunosupression for approximately a year post BMT
• Days -2, -1: Rest 
• Day 0: Bone marrow Harvest and Transplant Day
• Day +1: Methotrexate (GVHD prevention)
• Day +3: Methotrexate (GVHD prevention)
• Day +5: Rituximab (EBV prevention)
• Day +6: Methotrexate (GVHD prevention)

As I have said before, I am surprised by how smoothly the pre-conditioning phase went. He was very sleepy on days -5 through -2, likely due to high doses of benadryl as much as chemo effects. He felt sick and had three bouts of vomiting on days -4 and -3. He started to bounce back by around day 0 and has been increasingly active ever since, certainly nowhere near his old self but still we spend a good amount of time in the halls every day walking and playing with his beach ball or in the room playing board games and doing crafts. He loves spending time with the volunteers and the music and art therapists too.

On the evening of day 6, we noticed his hair starting to fall out and will likely shave his head (per his request) sometime over the next few days. Nathan hasn't had any mucusitis or any other major post-chemotherapy effects to date and I am told it is unlikely that he will at this point just due to the time that has passed and the "reduced intensity" regimen that he has had. His liver enzymes have gone up a bit due to the recent methotrexate doses but that is normal and the numbers will go back down as quickly as they went up. The only other not so great effect is that he is consuming platelets rapidly once again likely due to the ATG but that also should be just a temporary issue that will remedy itself just like it did the last time he received this medication. Now we just have to wait for the new cells to grow which can begin to happen as early as day 10 or as late as day 24, and then hope there aren't any major complications following engraftment so we can finally start planning to go home.

Post-Transplant Update

Nathan's bone marrow transplant was yesterday. It was an exhaustingly full day for all of us. Camryn had her marrow harvested at noon and she was so brave and very peaceful but for a few tough moments. We are all incredibly proud of her. She was woozy waking up from anesthesia and a bit sore as well so it took her a while to get back on her feet again. They got back to Nathan's room just moments before her cells began going into Nathan's picc line at 5pm. And of course, by this time, he was crabby and exhausted. I think the events of the day, anxiety, tiredness, hunger, elevated blood pressure and low hemoglobin took their toll on him. It felt like the perfect storm of crabby moods and overwhelm for all of us. Suffice it to say that it wasn't the picturesque rainbows and unicorns sibling transplant that one may envision (albeit unrealistically) but it is done and the cells are in him and both kids are doing great today. And that's what matters most.

Now we get to move forward. We have a good week of waiting for any delayed chemo effects such as mucositis (not very likely) and hair loss (all but inevitable), then another couple weeks waiting and hoping for signs of bone marrow growth. And then the other complications like graft vs. host disease may begin to rear their ugly head. In the meantime, he will continue on whatever medications and transfusions he needs to manage his symptoms and keep him as strong as possible through this. He surprises me with his strength and resilience and his great spirits. Even in his crabbiest moods, which are very rare, he is able to snap out of it and find his own balance remarkably well. He hasn't been home in over three months and I think we are all managing amazingly well considering how intense each day is. We just need to hold on a bit longer and imagine those beautiful stem cells finding their home and growing a perfectly functioning new "blood factory" for Nathan so we can finally begin to plan our journey back home.

And now we rest!

Nathan's four day round of chemotherapy pre-conditioning is over! Now he has two days of rest before his transplant day on Monday. I was really worried about how he would feel on chemo but it really wasn't as bad as I had thought it would be. He had lots of ups and downs for sure but it seemed the first two days were the hardest on him. He mostly slept a lot and had a few intermittent bouts of diarrhea and some vomiting too. On days three and four, he began to perk up and feel a bit better so I hope these two rest days will give him the strength he needs for the next part of his journey. The post-transplant effects are highly variable. He can feel great and have very few of relatively minor issues or he can have a whole host of complications in the forms of serious graft-versus-host disease and delayed chemotherapy side effects. The next month will be critical. I am nervous yet also very excited.

A few people have asked what medications he is on and I will warn that it is a very long and intimidating list, and I am likely forgetting at least a couple medications as it is very difficult to keep track of the daily changes. I am guessing these words won't mean anything to most people except maybe those in the medical field or other BMT patients. His chemotherapy medications over these past four days were Fludarabene, Cytoxan and R-ATG. To support his body through the chemotherapy phase, he also was given Decidron which is a steroid that reduces his risk of reacting to the ATG as well as Benadryl for the same purpose and Mesna to protect his bladder. All of those medications are done now but he is continuing on a high dose of Tacrolimus (similar to Cyclosporine) to suppress his t-cells so they do not attack the new stem cells upon transplant. In addition to these key conditioning medicines, there is a whole host of medicines that he will continue on in order to manage side effects and reduce the risk of infections and viruses while his immune system is suppressed. These include antibiotics (Pipercillin-Zosan), antifungals (Micafungin), antivirals (Acyclovir), antacids (Lansoprazol and Ranitidine), Zofran for nausea, Amlodopine and Enalapril to control his blood pressure, Ursidiol to support his gallbladder, Hydrocortisone to support his adrenals through the transplant, Heparin to protect his liver and a high level of IV fluid maintenance with supplemental magnesium and potassium added. Soon he will begin new medications to address any post-transplant complications and also reduce the risks of various other effects... namely Methotrexate to prevent GVHD, Rituximab to prevent EBV and periodic IVIG transfusions to boost his immune system. Unfortunately both methotrexate and Rituximab are considered chemo drugs, albeit without the traditional chemo effects and in significantly lower doses in this case, but still our time with chemo isn't quite over yet. And then there are all of the unknowns post transplant that will have to be controlled for as issues arise. It's overwhelming to think of this list of complications and medications but it is what it is and all of it is temporary. Suffice it to say, a bone marrow transplant is kind of a big deal.

Three months

Today, September 19th, marks three months since this journey began. 13 weeks plus one day. Nathan and I haven't been home in 92 days total; 71 in the hospital and 21 at the Ronald McDonald House. Many many more days to go still before we will go back home again.

Three months since our world was rocked to its core, since we found out that Nathan was so very sick, since our hearts were broken then immediately expanded exponentially... I guess sometimes things need to break to make room for real growth. Instantly we possessed love and strength that we never thought humanly possible;  love and strength that we would find ourselves clinging to in order to sustain this ordeal.

Three months of waiting and trying to figure out exactly what was truly going on and how to best treat him. Stress, anxiety, a variety of possible diagnoses and finally the official diagnosis presented itself. Thrilled that we have something to treat but terrified that the treatment can be as challenging as the disease.

Three months and we have a whole new vocabulary of terms that would have previously meant nothing to us but now these simple words can make or break our days.

Three months and we are longing to be back home again but knowing that our "home" will never be quite the same, there is no going back to the way things once were. Yet still, we are together, that is what matters most. And we have an extended group of friends and family who has lifted us up and taken such great care of our basic needs; of nurses who have become like family for their love of our sweet little boy, and doctors who have worked tirelessly to make sure that they select the right treatment for him. Home means something very different to us now. Home is where our family is and where love resides so this must be our home for now.

Three months that nearly feel like a lifetime, and I guess it should feel that way, for we are all completely transformed by this experience.

Three months of hope and counting our many many blessings because, despite everything, there is still so very much to be thankful for. But we are also exhausted to the core yet knowing that some of our toughest days are still to come. No five year old should have to fight for his life and endure the many difficult procedures and medications that offer his only really hope of recovery. No seven year old should be asked to step up and save her brother's life. No parents should have to watch a child slowly lose his strength and drift away... a child that was just recently healthy and strong and vibrant. But we must be on this path for some reason and maybe, once we have the luxury of hindsight, that reason will be abundantly clear to us. In the meantime, we have been here for three months... and counting. 

The Transplant Journey Begins

Today was Nathan's first day of chemotherapy. In a previous post, I described his planned conditioning and bone marrow transplants regimen in detail. I refer to it as clearing out the cobwebs of his nearly empty bone marrow to make room for his sister's stem cells to move in. In truth, it is poison. As someone who avoids toxins and generally likes to live a clean life, it is humbling and sobering and sometimes even terrifying. Yesterday he became sick due to an unusual reaction to a blood pressure patch that we started a few hours earlier. I joked that I was getting an early taste of chemo side effects and it seems that this joke was pretty close to reality. Today he seems to be overloaded and, while we didn't expect him to really start feeling really sick for nearly a week, it appears as though his body is feeling some minor effects of the chemotherapy already on day 1. Now we haven't experienced any scary side effects but it is clear that he is very fatigued and definitely not feeling well. I am hoping that this is the extent of it and that he will simply "sleep it off" but it is tough to see my formerly active and exuberant little boy feeling so sleepy and lethargic. I am not sure what to expect for the next three days of conditioning (much less the days beyond his transplant) but I am at least glad that we haven't seen any of the early anaphylactic or otherwise truly life-threatening effects. There are always blessing to be had in every moment, even the really tough moments when you are slapped with some harsh realities. Nathan is sick, very very sick, and the treatment is no walk in the park either. But there is a light at the end of the tunnel. September 22nd is his transplant date and then we can begin his journey towards healing. We are as ready as we can be and hoping to just hold on and keep on swimming. We may be tearing him down now but there is always time to build him back up again after this is all over. And that's what I keep reminding myself of. As with everything, "this too shall pass" and I just need to breathe and envision brighter days ahead.

Planning for a Bone Marrow Transplant

"It's empty!" Those words, the words of our doctor when referring to Nathan's bone marrow, were not at all unexpected. We are five weeks from his ATG treatment and he should be showing some early signs of growth given all of the white cell stimulant (both g-csf and gm-csf) he has been given each day. But thus far nothing has changed in his daily labs, no growth, nothing indicating to us that he is showing even a minor response to the treatments. His bone marrow is just "empty", officially having less than 5% (essentially immeasurable) cellularity, so his lack of progress makes sense given that there is effectively nothing to build from. On the plus side, nothing out of the ordinary was seen on his biopsy, no histiocites, nothing growing that shouldn't be there. And the ATG worked a small miracle on his liver inflammation. And he is still very happy and experiencing minimal complications or discomfort. And these are all really good things. Now it very much feels like the time to plan for the next steps... a bone marrow transplant. I'm going to go into detail regarding some of the preparation that we are looking at in the next couple of days.

Tomorrow Nathan will begin all of the preparation to clear him for transplant. This includes a series of exams to ensure that all of his organs are healthy which includes a CT scan, a GFR test for his kidneys, an echocardiogram, a pulmonary exam, a comprehensive series of blood tests and a dental exam. He will also need another PICC line in his other arm as he will need four access points for all of his conditioning. And of course he will also have a psychological and physical therapy evaluation. And we will switch to a different room that is specially cleaned and prepared for a bone marrow transplant patient. I asked for a room with a sunrise view since Nathan just loves to watch the sun rise; if we are going to be stuck in our room again while waiting for his immune system to grow, we may as well have something beautiful to wake up to!

Camryn is all but cleared to be his donor, and we are just waiting for a few minor pieces of paperwork to be completed. She has had several physicals, two huge blood draws (22 vials in total), and a psychological evaluation. She is of course anxious and wishes he would get better without going through the transplant, but don't we all? She is also very willing to overcome her fears and anxieties to help her brother get better knowing that this is his best chance at recovering and getting back home again. But this is a big deal for her and we are hoping as much as we can to make it a positive experience for her so she remembers her courage first and foremost.

Once both of them are cleared, then the real work will begin. He will start a four-day round of chemotherapy using cytoxin, fludarabine and R-ATG likely before the end of the week. This is considered reduced intensity conditioning for a bone marrow transplant. However, while most regimens for an identical HLA matched sibling would not include fludarabine, Nathan has enough abnormalities in his illness and has had a huge number of transfusions so it makes sense to include this additional medication to ensure that engraftment occurs. After the chemotherapy is complete, we have two rest days and then the transplant occurs. The actual bone marrow harvest from Camryn will essentially be very similar to a bone marrow biopsy except the needle is different and more fluid will be extracted; Camryn will be sedated and then a weight-appropriate amount of her bone marrow aspirate will be removed with the whole process taking less than an hour. After the procedure, her aspirate will be processed and prepared for the transplant to occur most likely the same day. I am told that transplant day will be pretty uneventful for him as he is simply getting a bag of his sister's bone marrow aspirate which will look like blood and it will effectively go into his system through his PICC line just like a blood transfusion. Then we wait... and hope that chemotherapy side effects will be minimal as the doctor suspects given his "reduced intensity" regimen. However, bacterial and fungal infections, viruses and graft vs. host disease are huge risks in the initial weeks following transplant and there seems to be a very rigorous protocol to reduce these risks. He will get a lot of medications to control complications during this time. Then hopefully within a few weeks, we will see his blood counts increase and we can begin planning for the future. But, during this time, he will be very severely immunocompromised and we have made decision to not allow any visitors until he has at least a few white blood cells and neutrophils to protect him. This could take days or weeks to even begin happening... there's no way to know right now exactly how it will go. 

I have felt for a long time that this is where we were headed but I really appreciate the doctors doing their due diligence because it really feels like everything is coming together at just the right time. Getting genetic testing back that rule out major genetic triggers like HLH or a GATA2 defect, our primary and favorite BMT doctor being on staff the majority of the month, Camryn feeling truly ready to do this major thing for her brother, his liver healing, and even small things like getting a visit from our "Make a Wish" wish granters all within the past week... it seems like everything is falling into place to ensure his successful recovery and that is the most that any of us can hope for. 

At the same time, reading through the paperwork outlining his regimen is very sobering. Effectively it states that his disease will result in his death but that the treatment could also result in his death... thats a huge pill for a mom to swallow. But it's not as though we have a real choice in the matter either. And his doctor, if I haven't said so already, is incredible. It is rare to have a doctor who will sit and really talk with you, collaborate, think outside the box, consider protocol but really look at the child in front of him first and foremost. I feel very fortunate that we have one of those doctors and I think I may be his biggest fan right now. I have to continue to trust that Nathan is in great hands and surrounded with the right team of people to help him get well again because he truly is, and the rest is completely out of our hands. We just have to hope that all will be well. 

So I'm going back to a poem that I have read many times through this journey...

"Hope" is the thing with feathers— 
That perches in the soul— 
And sings the tune without the words— 
And never stops—at all— 

And sweetest—in the Gale—is heard— 
And sore must be the storm— 
That could abash the little Bird 
That kept so many warm— 

I've heard it in the chillest land— 
And on the strangest Sea— 
Yet, never, in Extremity, 
It asked a crumb—of Me.

~Emily Dickinson

Riding the Roller Coaster -- Four Weeks Post ATG

This past week has been a roller coaster of sorts. Nathan is increasingly bored from having been in isolation for nearly four weeks and we have been effectively just hanging around and waiting. It has been difficult to keep him busy and happy within the confines of these four walls and, if I'm being honest, I'm pretty bored too. Suffice it to say that life here was quite uneventful... until this past Friday when Nathan spiked a fever and his other vital signs showed signs of stress, plus he stayed in bed sleeping the entire day which is very unusual for him. Of course the doctors were concerned because he has no ability to fight infection so he was given a CT scan to check his sinuses and lungs (all clear) and blood cultures were drawn to see if any bacteria was present (also negative). It seems he was simply having a bit of a reaction to weaning off steroids, which I had initially suspected as the cause of his illness given his lack of any outward signs of infection. A stress dose of hydrocortisone seemed to perk him up quickly but he was also placed on a few broad spectrum antibiotics until the blood cultures were confirmed to be clear as well as a systemic anti fungal, thankfully without any major side effects to date. That was much action for one day and I joked that it was a nine bead day; he was quite excited to add all those new ones to his beads of courage. So my point is that I much prefer being bored. And here we are today, bored again, but I'm sure we will have many ups and downs to come.

Clinical Update

From a clinical perspective there is effectively no change in his aplastic anemia. His body doesn't seem to be showing any signs of responding to the ATG treatment and we are now four weeks since he received his last dose. Seems we are indeed headed down the path of a bone marrow transplant and thankfully Camryn and Nathan are perfect sibling matches which is a huge blessing that I talked about at length here and here. Lots of tests and evaluations will occur in the next 1.5 weeks and I am glad that our primary BMT doctor is the attending physician in the hospital HOT (i.e. hematology oncology & transplant) unit this week as I will feel most confident having him here to make all of the day to day decisions leading up the transplant decision and preparation. We continue to wait for some genetic testing but we did find out that he does not have the GATA2 genetic mutation that they suspected some time ago. I am not sure if I'm relieved or sad at this news, clearly something lead to this illness and it sure would be nice to be able to name it, but I can't dwell on that right now. 

Blood Counts
WBC: 0.3  (4.0-12.0)

Neutrophil Count: 141 (1400-1600)

RBC: 3.41 (4.0-5.3)

Hemoglobin: 9.9 (11.5-14.5)
He received a RBC transfusion three days ago.

Platelets: 22 (150-450)

He is getting platelet transfusions every 1-2 days and will get a transfusion again tomorrow as his counts will definitely be in the single digits once again.

Liver Inflammation

AST: 16 (23-58)

ALT: 98 (6-35)

Total Bili: 1.0 (0-1.1)

We likely won't continue to track these numbers as they are effectively normal now.

Medication Notes

While it looks like we are heading closer to a bone marrow transplant, our doctor wanted to try one more medication to see if he could stimulate white cell growth. Nathan is now on both G-CSF and GM-CSF and still his neutrophil and white cell counts are stagnant and showing no real signs of life. His Tacrolimus level has stayed more consistent now at a dose of 10ML. Given his reaction to the steroid weaning, his steroids have been increased again and we are starting the slow weaning process once more, hoping he doesn't bottom out again. He continues on one antibiotic to inhibit bacterial growth and has added Micafungin to inhibit fungal growth as well as medications for his elevated blood pressure (due to tacro) and acid reflux (due to steroids). I don't love the idea of treating an illness and then treating the side effects of the treatment, but it seems that is where we are right now. Bone marrow failure is serious to say the least and the treatment options seem to match the severity of the illness. I am quite certain that our post transplant regimen (assuming we do in fact go in that direction) will be quite intense. But it is all worth it to heal Nathan and get my sweet little guy back home again. There will be plenty of time to work on building his system back up again when this is all behind us. 

Much love to all of our friends and family!