"A disease or disorder is defined as rare in the USA when it affects fewer than 200,000 Americans at any given time." - http://www.rarediseaseday.org/article/what-is-a-rare-disease
Earlier this week I received an email saying 28 Feb was rare disease day. I didn't think much about it until today.
Elise has had a dry cough this entire week. I think it's just a scratchy throat from a sinus infection. She isn't running a fever but the cough hasn't gotten better, and last night it kept her awake most of the night. I decided to keep Elise at home today. mostly so she could sleep (she finally fell soundly asleep around 5:15 am).
[It's kinda ironic, but despite Elise's CGD she has had very few actual sick days from school. Maybe as few as one each year. The vast majority of her days missing school have been medical appointments at UCLA or NIH. Even when she's has a severe colitis flare up she hasn't missed school. She even went to a 5-day camp during one colitis flare. She's a tough little girl.]
In any case, today was a good day to keep her home: she slept until 10:45 am which is about 4 hours later than she ever sleeps.
I decided to make an appointment to see a primary care physician. Her physician since birth retired recently and so we are trying someone new and it struck me then what it means to have a rare disease. I had to prepare an updated list of medicines she's currently taking or recently taken (6 pages). I needed to print out a list of medical contacts - 2 pages of specialists she's seeing. And the kicker: I have to print out a description of CGD from medline so that the Dr. understands what CGD actually is. It's not their fault, a doctor could practice an entire career and never encounter it. But it's just a sample of what it can mean to have a rare disease even for seemingly routine appointments.
All variants of CGD combine affect about 1 in 200,000 people (there are 4 main types of genetic anomalies that cause CGD). The type that Elise has affects something like 1 in 1,000,000 people. So there are about 300 people in the US who have the same type of CGD as Elise. I'd call that "rare".
Friday, February 28, 2014
Saturday, February 22, 2014
A Long Trip For An Important Meeting
Elise and I went to NIH this week for the apheresis procedure. The plan was to collect her stem cells and store them as a backup in case the donor cells don't implant - her own stem cells could be used to reboot her immune system. It's really a backup to a backup because the non-myeloablative conditioning regimin they plan to use is designed to leave some of her immune system intact. What remains should be able to recover if the donor cells don't engraft. So this is really a remote risk mitigation procedure, and I'm told most other transplant centers don't take this step.
In summary, the procedure was cancelled because her stem cell count didn't rise in response to the special meds they use so there was little or nothing to collect. Bummer.
At this point the team thinks the problem Elise encountered was one of two things: 1) the anakinra injections she's been on interfered with the GCSF injections even though we'd held the anakinra for 2 days before starting the GCSF; or 2) her body just doesn't respond to GCSF like most people. They don't have any experience with anakinra, but they did suspect there would be some interaction (which is why they stopped it 2 days prior).
So the plan now is to either try apheresis again in 4-6 weeks (withholding the anakinra for 2 weeks prior vs 2 days) or just skip the collection of the backup stem cells. The latter makes some sense since it's really a backup for a backup, and in fact they've never had to use it. But the overall number of situations where they might potentially need to use the backup are real low (2 cases of non-engraftment), so statistics can be computed but probably aren't relevant. Becky and I are leaning towards the former (ie redo the apheresis process) simply because Elise seems to always fall into the 1% who have problems. We call it "Bechtel Luck".
Elise was pretty upset when they decided to cancel the apheresis. She was exhausted from getting a 9pm injection of Plerixafor and then woken at 4am for the last GCSF injection, and then bloodwork at 6am with a nosebleed in between. She wanted to know why they didn't just go directly to a bone marrow harvest process (which is an option, but painful and very invasive). She just wanted it to be done and over with. The good news is it meant she had really read the consent paperwork because this approach was listed as an option, but we'd never discussed it.
We rescheduled our travel and came home a day early. As a result Elise was able to get a day of school in this week and also attend a dance on Friday evening at the teen center.
So this all sounds like a wasted trip, but I don't feel like it was. First off we had an hour conference with the transplant team. We went through the process and all the ins and outs. They answered questions we'd dreamed up over the past many weeks and in general reduced my stress level a notch (from 11 to 10 on a 10 point scale). Becky was able to dial into the conference and hear directly what I did so we can compare notes. Also, we got a few days of practice at being inpatient in the wing where Elise will be living for 6+ weeks. That gave me a good feel for what to plan for. And lastly, Elise met another 13 year old girl from New York with an immune deficiency. They became quick friends and have started texting one another.
So I wasn't as disappointed as Elise, but then I'm not the one being poked and prodded.
In summary, the procedure was cancelled because her stem cell count didn't rise in response to the special meds they use so there was little or nothing to collect. Bummer.
At this point the team thinks the problem Elise encountered was one of two things: 1) the anakinra injections she's been on interfered with the GCSF injections even though we'd held the anakinra for 2 days before starting the GCSF; or 2) her body just doesn't respond to GCSF like most people. They don't have any experience with anakinra, but they did suspect there would be some interaction (which is why they stopped it 2 days prior).
So the plan now is to either try apheresis again in 4-6 weeks (withholding the anakinra for 2 weeks prior vs 2 days) or just skip the collection of the backup stem cells. The latter makes some sense since it's really a backup for a backup, and in fact they've never had to use it. But the overall number of situations where they might potentially need to use the backup are real low (2 cases of non-engraftment), so statistics can be computed but probably aren't relevant. Becky and I are leaning towards the former (ie redo the apheresis process) simply because Elise seems to always fall into the 1% who have problems. We call it "Bechtel Luck".
Elise was pretty upset when they decided to cancel the apheresis. She was exhausted from getting a 9pm injection of Plerixafor and then woken at 4am for the last GCSF injection, and then bloodwork at 6am with a nosebleed in between. She wanted to know why they didn't just go directly to a bone marrow harvest process (which is an option, but painful and very invasive). She just wanted it to be done and over with. The good news is it meant she had really read the consent paperwork because this approach was listed as an option, but we'd never discussed it.
We rescheduled our travel and came home a day early. As a result Elise was able to get a day of school in this week and also attend a dance on Friday evening at the teen center.
So this all sounds like a wasted trip, but I don't feel like it was. First off we had an hour conference with the transplant team. We went through the process and all the ins and outs. They answered questions we'd dreamed up over the past many weeks and in general reduced my stress level a notch (from 11 to 10 on a 10 point scale). Becky was able to dial into the conference and hear directly what I did so we can compare notes. Also, we got a few days of practice at being inpatient in the wing where Elise will be living for 6+ weeks. That gave me a good feel for what to plan for. And lastly, Elise met another 13 year old girl from New York with an immune deficiency. They became quick friends and have started texting one another.
So I wasn't as disappointed as Elise, but then I'm not the one being poked and prodded.
Sunday, February 16, 2014
G-CSF aka "Filgrastim"
Elise started the first of five days of subcutaneous injections of granulocyte-colony stimulating factor (GCSF) or "Filgrastim". There are 2x 1ml injections and these must be done around 6am each morning. We've got a few things going for us: 1) she got to stop the Kineret injections while she gets the GCSF; 2) the GCSF serum doesn't burn after injection like the Kineret (yeah!); and 3) this morning she got up to go to the bathroom on her own around 6am so I didn't have to face a grumpy child with a syringe. Much to my surprise, Elise went back to sleep after the injections. Guess it's just not that much drama for her anymore.
According to the documentation, GCSF is a "haematopoetic growth factor". It stimulates the bone marrow to produce more white blood cells and stem cells, and they collect these during the apheresis procedure.
I'm waiting for the potential side effects of GCSF to kick in: bone pain; itchy skin near injection sites; fever, chill and fluid retention; and the multi-purpose side effect: nausea, vomiting and diarrhea.
We get to do these injections until she has the apheresis this coming Thursday. We'll travel out on Tues to NIH, check into the hospital that evening, have tests on Wed, then on Thu she'll have a venous catheter placed and they'll do the apheresis. If all goes well then they'll remove the catheter and we'll fly home on Fri.
We're going into/out of Dullas airport this time so maybe we'll swing over to the Udvar-Hazy Smithsonian for a couple hours on Friday since our flight isn't until 5:30pm. They say she'll likely be fatigued from the apheresis so she may not be up for this though.
This getting up at the crack of dawn has its upside: I went for a hike in the foothills around our house and got to see a beautiful sunrise.
Friday, February 7, 2014
Understanding The Treatment Process
During the pre-apheresis visit they handed me the consent document for the transplant process. They wanted me to take it home and read it before we returned for apheresis. I read it last night. I couldn't sleep after that. All the drugs and the associated risks are mind bending. Imagine reading back-to-back all the possible side effects from all the medications and medical procedures you've ever taken/had and then consider chosing to expose your child to all of them in one concentrated period of time. It's emotionally disturbing.
The consent lays out the process and all the significant risks and side effects of the medications they typically use as well as the possibility of graft vs host disease (GVHD) and what that might mean. It's some seriously scary sh*t.
Here is the summary of the treatment plan. In general, the NIH protocol is meant to minimize the toxicity of the treatment and the reduce the chances of GVHD while providing a reasonable chance of success. The tradeoff is that the risk is increased that the donor cell do not successfully engraftment, meaning the intent of the overall process fails.
1. Apheresis
2. Preconditioning examinations
3. Pre-transplant conditioning
4. Transplant
5. Pre-engraftment prophylactic measures
6. Post-engraftment prophylactic measures
7. Long term follow-up
I've already talked about apheresis. There are risks but they are relatively minor. The exams are a full battery begins to make sure she's healthy enough to proceed.They also insert a Hickman Intervenous line so that they can get IV stuff into (and out of) her veins during the long term process without endless needle sticks. This line will stay in until the +100 day mark. This happens the week before the pre-transplant conditioning begins.
Pre-transplant conditioning takes about two weeks. First they start with a drug called Paliferman which reduces the impact of mucositis (painful sores in the mouth) caused by the conditioning process. Next she'll have 5 days of an immunosuppresant called Alemtuzumab ("Campath"). After that she'll get two days of low dose Busulfan which will kill the germ fighting cells of her immune system. They also use a anti-seizure med (Clonezepam) at this point because Busulfan can cause seizures. Next she may receive a couple "low" doses of total body irraditation (TBI). Finally they start a drug called Sirolimus ("Rapamycin") to prevent GVHD. She'll continue to take a tapering dose of Sirolimus to help prevent GVHD for up to 6 months following the transplant.
After the conditioning they do the stem cell transplant. Everyone says its anticlimactic: basically like a blood transfusion. They hang a bag of the donor's stem cells and infuse them over several hours.
For (nominally) 30 days after the transplant she'll stay in the hospital and be closely watched for infections since she'll essentially have little or no immune system. Apparently this is the worst period of discomfort for the patient with fevers, nausea, diarhea and mouth sores all possible. If infections crop up (and I'm told they will) she'll be treated with antibiotics, etc. She'll also probably have some transfusions along the way. I believe they also use some prophyllactic antibiotics and antifungals during this period.
The signs of initial engraftment typically occur in about 14-21 days. They'll be doing tests to monitor this.
After 30-45 days Elise's new immune system will hopefully have recovered enough to have some ability to fight off infections - enough that she can be released from the hospital. From that point until around transplant+100 days we'll need to stay close to the hospital so that she can be seen frequently by the medical staff. During this phase she'll be taking antibiotics and antifungals as well as the medication to prevent GVHD.
At about 100 days after the transplant most patients are ready to go home. The treatment will continue but eventually she'll be weened off most of the meds. We'll transition to a monitoring/treatment by a medical team that is closer to home. It's possible that a wide variety of things can happen after 100 days, but statistically this is apparently a significant milestone for the average patient.
The consent lays out the process and all the significant risks and side effects of the medications they typically use as well as the possibility of graft vs host disease (GVHD) and what that might mean. It's some seriously scary sh*t.
Here is the summary of the treatment plan. In general, the NIH protocol is meant to minimize the toxicity of the treatment and the reduce the chances of GVHD while providing a reasonable chance of success. The tradeoff is that the risk is increased that the donor cell do not successfully engraftment, meaning the intent of the overall process fails.
1. Apheresis
2. Preconditioning examinations
3. Pre-transplant conditioning
4. Transplant
5. Pre-engraftment prophylactic measures
6. Post-engraftment prophylactic measures
7. Long term follow-up
I've already talked about apheresis. There are risks but they are relatively minor. The exams are a full battery begins to make sure she's healthy enough to proceed.They also insert a Hickman Intervenous line so that they can get IV stuff into (and out of) her veins during the long term process without endless needle sticks. This line will stay in until the +100 day mark. This happens the week before the pre-transplant conditioning begins.
Pre-transplant conditioning takes about two weeks. First they start with a drug called Paliferman which reduces the impact of mucositis (painful sores in the mouth) caused by the conditioning process. Next she'll have 5 days of an immunosuppresant called Alemtuzumab ("Campath"). After that she'll get two days of low dose Busulfan which will kill the germ fighting cells of her immune system. They also use a anti-seizure med (Clonezepam) at this point because Busulfan can cause seizures. Next she may receive a couple "low" doses of total body irraditation (TBI). Finally they start a drug called Sirolimus ("Rapamycin") to prevent GVHD. She'll continue to take a tapering dose of Sirolimus to help prevent GVHD for up to 6 months following the transplant.
After the conditioning they do the stem cell transplant. Everyone says its anticlimactic: basically like a blood transfusion. They hang a bag of the donor's stem cells and infuse them over several hours.
For (nominally) 30 days after the transplant she'll stay in the hospital and be closely watched for infections since she'll essentially have little or no immune system. Apparently this is the worst period of discomfort for the patient with fevers, nausea, diarhea and mouth sores all possible. If infections crop up (and I'm told they will) she'll be treated with antibiotics, etc. She'll also probably have some transfusions along the way. I believe they also use some prophyllactic antibiotics and antifungals during this period.
The signs of initial engraftment typically occur in about 14-21 days. They'll be doing tests to monitor this.
After 30-45 days Elise's new immune system will hopefully have recovered enough to have some ability to fight off infections - enough that she can be released from the hospital. From that point until around transplant+100 days we'll need to stay close to the hospital so that she can be seen frequently by the medical staff. During this phase she'll be taking antibiotics and antifungals as well as the medication to prevent GVHD.
At about 100 days after the transplant most patients are ready to go home. The treatment will continue but eventually she'll be weened off most of the meds. We'll transition to a monitoring/treatment by a medical team that is closer to home. It's possible that a wide variety of things can happen after 100 days, but statistically this is apparently a significant milestone for the average patient.
Thursday, February 6, 2014
Pre-Apheresis Visit
Elise and I flew to the DC area on Sunday for a visit to NIH on Monday & Tuesday for a pre-apheresis exam and blood test. After watching the Bronco's give up a huge number of points to the Seahawks in the Superbowl Sunday night, we had appointments all day Monday. We met a bunch of different people that work on the transplant team. We also met with the social worker to discuss some of the logistics of temporarily relocating.
There is so much to learn and understand. Being a mathematician doesn't help me understand the process and medications very well - I took high school biology and that's about it. The drug names and uses that are everyday vocabulary to the professionals mean nothing to me. So its really hard to ask good questions. It doesn't help that I've never thought well "on my feet" - I do much better to read, research and then think a bit before I ask questions.
Elise will go through apheresis in a couple weeks to collect her own stem cells. It's the same process the donor will go through. Elise is going through it so that there is a back-up to reboot her immune system if the donor cells don't engraft. Since the process she'll undergo is nonmyeloablative (it won't entirely destroy her bone marrow) I think her system could possibly recover without the backup, but I guess its an added precaution. I'm told that they've never had to revert to the backup at NIH. I'm also told that other transplant centers don't take this added step. But it gives me some peace of mind to know that they're trying to minimize the risk for Elise.
In another week Elise will get 5 days of granulocyte colony-stimulating factor (G-CSF) injections which will migrate her stem cells from her bone marrow to her blood stream. Then they insert a catheter and hook her up to the apheresis machine for about 5 hours to harvest the stem cells. We visited the room where they do the apheresis process and the nurse showed us around. They measured Elise's veins and decided she'll probably need a jugular catheter since the veins in her arms are too small. Placing the catheter is a "simple procedure", but they'll sedate Elise during it. Hopefully they'll collect enough stem cells in one session and then remove the catheter. There's a chance that they'll have to do two sessions, but apparently that's rare/never happened.
I think she's actually looking forward to the G-CSF subcutaneous injections because they want us to stop her current Kineret (anakinra) sub-Q injections 2 days before the G-CSF starts and then hold them through the end of the apheresis process. Kineret is painful to inject: the serum is slightly acidic so it burns for 5-15 minutes after its injected. We're told that G-CSF is just a normal needle stick (no post-injection burning) and Elise doesn't care about needle sticks after having so many.
We also confirmed that Elise will likely lose her hair due to the pre-transplant conditioning protocol. Another interesting thing is that her current allergies might change due to the transplant. She got pretty excited when she found out she might end up not being allergic to cats anymore. But I warned her there could be a downside too (it would be a real bummer if she became allergic to creosote bushes!) I love that she starts to look at the positive side of things after the initial shock: she's already starting to talk about getting her hair cut short before the transplant process starts.
The appointments all occurred on Monday, so on Tuesday we had to wait for the 4:50 pm flight back to CA. We took the shuttle to the airport first thing in the morning, checked our bag for our flight, and then took the Metro to the Smithsonian museum area. Elise likes the Museum of Natural History because they have bugs. She held a giant grasshopper and a hissing cockroach. The butterfly walkthrough enclosure is also free on Tuesdays so we did that. It's nice to do something fun after all the poking, prodding and sitting around on Monday. After that, the trip home was long but uneventful.
So we'll be back to NIH on the week of 18 Feb '14 for the apheresis procedure.
Saturday, February 1, 2014
Rough Transplant Timeline
This is the rough timeline for Elise's stem cell transplant. The dates could easily change along the way.
3-4 Feb '14: pre-apheresis checkup and tests
16-20 Feb '14: pre-apheresis injections of granulocyte colony-stimulating factor (G-CSF) (aka Filgrastim)
18-20 Feb '14: apheresis - the process is described here
week of 11 May'14: travel to Bethesda, MD and set up apartment
week of 18 May '14: Hospital admission and tests
week of 25 May '14: Pre-transplant "Conditioning" begins
"Conditioning" includes chemotherapy and possibly radiation therapy. Chemotherapy and radiation destroy the blood-forming cells in the bone marrow to make room for your new cells. They also destroy the immune system so it can’t attack the donated cells after transplant.
The effects of the conditioning can range from mild to severe. Common symptoms resulting from chemotherapy and radiation include nausea, vomiting, diarrhea, hair loss, fatigue, loss of appetite and mouth sores. Some people develop all of these conditions whereas others develop only a few of them.
around 6 June ' 14: Transplant day ("Day 0")
7 June - 7 July '14: Pre-engraftment period (Day 0 - Day 30)
Engraftment is when the newly infused cells begin to reproduce within your body. Often the first sign of engraftment is a rising white blood cell count. For a peripheral stem cell transplant (most likely), engraftment will usually occur within 10-15 days post-transplant.
This is a very risky period as Elise will essentially have no immune system function making her prone to bacterial and viral infections. Additionally, as Elise's white count rises, she may experience graft versus host disease (GVHD). Graft versus host disease occurs when the white cells produced by the donor’s transplanted cells do not recognize the new organs and tissues as “self”. This happens because there are some genetic differences between the donor and recipient. Because of these differences, the new immune system may identify the host cells as foreign and will attack them.
8 July - mid Sept '14: Post-engraftment period (Day 31 - Day 100)
During this period, Elise will check out of the hospital and we'll all stay at an apartment in Bethesda, MD near to NIH so that we can make frequent, possibly daily, trips to NIH.. Her immune system will be gradually building. If she has GVHD it will be treated and any infections will be addressed immediately. She may need periodic transfusions. It's possible she could be readmitted to the hospital during this period. Elise will also have a tutor for school work during this period.
late Sept '14: travel home to Ridgecrest, CA (Day 100+) & follow-up care
The follow-up care could go on for a year or more depending on how Elise's system responds. Hopefully she'll be able to go back to school sometime during the fall semester, until then she'll have a teacher visit once per day to keep her on track with schoolwork.
3-4 Feb '14: pre-apheresis checkup and tests
16-20 Feb '14: pre-apheresis injections of granulocyte colony-stimulating factor (G-CSF) (aka Filgrastim)
18-20 Feb '14: apheresis - the process is described here
week of 11 May'14: travel to Bethesda, MD and set up apartment
week of 18 May '14: Hospital admission and tests
week of 25 May '14: Pre-transplant "Conditioning" begins
"Conditioning" includes chemotherapy and possibly radiation therapy. Chemotherapy and radiation destroy the blood-forming cells in the bone marrow to make room for your new cells. They also destroy the immune system so it can’t attack the donated cells after transplant.
The effects of the conditioning can range from mild to severe. Common symptoms resulting from chemotherapy and radiation include nausea, vomiting, diarrhea, hair loss, fatigue, loss of appetite and mouth sores. Some people develop all of these conditions whereas others develop only a few of them.
around 6 June ' 14: Transplant day ("Day 0")
7 June - 7 July '14: Pre-engraftment period (Day 0 - Day 30)
Engraftment is when the newly infused cells begin to reproduce within your body. Often the first sign of engraftment is a rising white blood cell count. For a peripheral stem cell transplant (most likely), engraftment will usually occur within 10-15 days post-transplant.
This is a very risky period as Elise will essentially have no immune system function making her prone to bacterial and viral infections. Additionally, as Elise's white count rises, she may experience graft versus host disease (GVHD). Graft versus host disease occurs when the white cells produced by the donor’s transplanted cells do not recognize the new organs and tissues as “self”. This happens because there are some genetic differences between the donor and recipient. Because of these differences, the new immune system may identify the host cells as foreign and will attack them.
8 July - mid Sept '14: Post-engraftment period (Day 31 - Day 100)
During this period, Elise will check out of the hospital and we'll all stay at an apartment in Bethesda, MD near to NIH so that we can make frequent, possibly daily, trips to NIH.. Her immune system will be gradually building. If she has GVHD it will be treated and any infections will be addressed immediately. She may need periodic transfusions. It's possible she could be readmitted to the hospital during this period. Elise will also have a tutor for school work during this period.
late Sept '14: travel home to Ridgecrest, CA (Day 100+) & follow-up care
The follow-up care could go on for a year or more depending on how Elise's system responds. Hopefully she'll be able to go back to school sometime during the fall semester, until then she'll have a teacher visit once per day to keep her on track with schoolwork.
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