Sunday, January 24, 2016
Wednesday, January 20, 2016
Latest results from Peter's visit to NIH
In late November, Peter and I spent a week at the NIH in Bethesda, MD so that he could be thoroughly studied as part of their research program on inherited bone marrow failure disorders. This was a wonderful opportunity for us to find out if there was anything going on that we didn't know about.
We stayed at the famed Children's Inn where we mingled with families from all over the world whose children were there for research studies or clinical trials. Peter's genetic disorder, Dyskeratosis Congenita, is exceptionally rare, but some of the other kids were the first known cases of their specific disorders. There were many children who had recently been through bone marrow transplants and were wearing masks against infection, and many others whose disorders were responding to novel therapies available only at the NIH.
We had up to 6 appointments a day for 5 days while we were there, and that was hard on Peter, but overall it was a really positive experience. He was grumpy towards me a lot of the time, but he handled it amazingly well considering all his challenges. He even tolerated having a tube with a tiny camera inserted up his nose and down his throat! (Well, OK, they sprang it on him really fast and he screamed bloody murder once he realized what had happened, but he only cried for a couple of minutes afterward and had a huge sushi lunch an hour later).
During my initial meeting with the study team, I finally learned that Peter's Dyskeratosis Congenita is caused by a splice mutation on his RTEL1 gene. This gene was only identified in 2013 by the doctors at NIH, so if we had gone earlier, we would have been in the "mutation undetermined" group. There are a small handful of other people in the world with RTEL1 mutations but he is the only one with his specific mutation.
People with the RTEL1 mutation are at an extremely high risk of tongue cancer. This type of cancer is very, very nasty and it is the last thing I want for Peter. The ENT group identified a small patch of pre-cancerous tissue on the bottom of his tongue and if it persists for more than a few weeks we will need to have it biopsied. I am examining his tongue weekly for other spots but I am not very good at recognizing them and it is critical to identify them early. So we will be seeing a good dentist for a complete check of his oral mucosa every 3 months from now on.
People with the RTEL1 mutation are also at an extremely high risk of blood cancers, particularly Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). As with Peter's overall bone marrow failure (which remains remarkably stable), the only treatment for MDS and AML is bone marrow transplant. I shared with the team our decision NOT to put Peter through a transplant given all his issues. They were very sympathetic and respectful, and emphasized that (as I had guessed) it would be highly unlikely for us to find a suitable donor for Peter anyway.
As I've mentioned before, Peter's telomeres (chemical "caps" on the DNA strands that help to maintain genetic stability as cells divide) are extraordinarily short. All people with Dyskeratosis Congenita have short telomeres, but his are among the very shortest they have seen. Our telomeres are at their longest when we are born, and they get shorter and shorter as we age. Peter's telomeres are like those of a 100-year-old person. This means he is extremely genetically unstable, a real ticking time bomb. He really should have been much sicker already.
It turns out that his Dyskeratosis Congenita (DC) is only one piece of his genetic puzzle. He has 2 or 3 other very significant mutations that will be studied, in time, by other geneticists at NIH. It's quite possible that these mutations haven't been seen before, so identifying them probably won't tell us anything. The geneticists at NIH feel that the totality of Peter's physical anomalies represent more than just the RTEL1 mutation. In other words, he has a lot going on due to his consanguinous parentage (incest between mother and father). It's even possible that one of the other mutations is somehow ameliorating the impact of the RTEL1 mutation, resulting in the unusual stability we've been seeing.
One thing we learned from our visit was that Peter has pretty severe osteoporosis from his total lack of testosterone. We decided not to give him a testosterone patch to induce puberty because he was resistant to the idea and -- more importantly -- his psychiatrist predicted that it would de-stabilize him in a most unpleasant way. The NIH doctors would like us to try a tiny piece of a patch to give him at least a little testosterone, because his osteoporosis is progressing quickly. We're not sure what to do, but will talk it over with his endocrinologist.
It was good to hear that we've been doing some things right. Peter's diabetes is very well controlled for his age, as is his hypothyroidism. He's been having his eyes examined regularly for diabetic retinopathy. We've treated his mood disorder as effectively as it can be treated. For a kid with his IQ, he is very functional and independent. Moreover, he doesn't live his life as a sick person. He doesn't have limitations and we keep him away from doctors and hospitals so he can just live his life.
When I talk about the stability of Peter's bone marrow failure, I mean that he has remained in essentially the same place for most of the past 8 years: modestly low white count and hemoglobin, and extremely low platelets (35-45). We had expected his immune function to decline and his anemia to get much worse by now, but it hasn't happened so far. Some parents would be all over their kids to avoid physical activity with platelets that low, for risk of bleeding. But we're not going to hover over him or wring our hands every time he leaves the house.
As we left the NIH, we had all of these results conveyed to us verbally and in a preliminary written report. The only thing we didn't know were the results of Peter's bone marrow biopsy on the next-to-last day. The last bone marrow biopsy was 5 years ago. If we were planning a bone marrow transplant we'd have been doing them every 6 months since then, but it's a major procedure with anesthesia and an incision where they punch through the hip to extract the marrow, and we're NOT planning a transplant. I was, understandably, very curious about how his bone marrow looks now.
Previously, Peter's marrow was found to be 5% cellular (95% empty). The team at NIH told me that this number could vary quite a bit depending on the specific spot where the cells were extracted. Bone marrow is not uniform. I had been wondering how he could be so stable with 95% of his bone marrow gone, but they said there were probably other places where the marrow had more cells and was working hard to keep his blood counts where they were. This time, his cellularity was measured at 20%, which is good news, so to speak.
On the other hand ...
Peter's bone marrow cells are no longer just sparse, but also abnormal. The abnormalities occur on all three lines: white cells, red cells and platelets. They took a sample of 20 cells and did a chromosome analysis on them to see if they showed mutations (evidence of genetic instability). 19 of the 20 were mutants with one arm of chromosome 7 broken off and joined to chromosome 1. Based on these results, it is clear that he now has intermediate-stage Myelodysplastic Syndrome, which as I mentioned earlier is a blood cancer.
The bone marrow failure study team has passed Peter's marrow over to the MDS experts at NIH to see if they can give us any further information. In the meantime, I did a deep dive in the literature and used the sophisticated life expectancy calculator on the MDS Association website to arrive at some prognostic information. As things are today, Peter's median life expectancy is 3 years, and he has a 44% chance of surviving 5 years. His chance of evolving from MDS to AML is about 60%. If that evolution happens, the median time for it to start happening is about 12 months.
When MDS turns into AML, it can happen in a matter of days, or it can take a few weeks or even a few months to go from initial signs to acute illness. The signs are exhaustion, weight loss, fever, loss of appetite. If the MDS doesn't turn to AML, then his blood counts will start to decline faster, and he will start to get infections, or need transfusions, or have bleeds due to his low platelets.
Back when Peter was first diagnosed, we thought he had a matter of months to live. But then he remained stable for a long, long time. Although I've been living with a grand piano over my head, the rope it's hanging on has been sturdy and I've learned to ignore it pretty well. Not that it's easy living with it, mind you. But what else can I do but live my life to the fullest and make sure that Peter lives his the same way? It's eventually going to fall, but it could be up there a long time.
Now the rope has clearly frayed and I am hearing tiny creaks from the piano. It will probably fall within the next 2-4 years, but it could fall much sooner. Or much later. It could creak and swing and scare us for weeks and months and years, or it could fall suddenly with no warning. For Peter's sake, I am hoping for the latter. I want him to be sick for the shortest possible time with the least amount of fear and suffering. I wish I could have some control over that, but alas, I cannot.
The Dyskeratosis Congenita group on Facebook is a great comfort to me, as are all the friends and family members who have been following Peter's journey with me. No parent should be in this position, knowing that her child's days are numbered and that she will have to walk with him fearlessly all the way to the end. And yet ... this is the path that lays before me.
Thank you for being here with me.
We stayed at the famed Children's Inn where we mingled with families from all over the world whose children were there for research studies or clinical trials. Peter's genetic disorder, Dyskeratosis Congenita, is exceptionally rare, but some of the other kids were the first known cases of their specific disorders. There were many children who had recently been through bone marrow transplants and were wearing masks against infection, and many others whose disorders were responding to novel therapies available only at the NIH.
We had up to 6 appointments a day for 5 days while we were there, and that was hard on Peter, but overall it was a really positive experience. He was grumpy towards me a lot of the time, but he handled it amazingly well considering all his challenges. He even tolerated having a tube with a tiny camera inserted up his nose and down his throat! (Well, OK, they sprang it on him really fast and he screamed bloody murder once he realized what had happened, but he only cried for a couple of minutes afterward and had a huge sushi lunch an hour later).
During my initial meeting with the study team, I finally learned that Peter's Dyskeratosis Congenita is caused by a splice mutation on his RTEL1 gene. This gene was only identified in 2013 by the doctors at NIH, so if we had gone earlier, we would have been in the "mutation undetermined" group. There are a small handful of other people in the world with RTEL1 mutations but he is the only one with his specific mutation.
People with the RTEL1 mutation are at an extremely high risk of tongue cancer. This type of cancer is very, very nasty and it is the last thing I want for Peter. The ENT group identified a small patch of pre-cancerous tissue on the bottom of his tongue and if it persists for more than a few weeks we will need to have it biopsied. I am examining his tongue weekly for other spots but I am not very good at recognizing them and it is critical to identify them early. So we will be seeing a good dentist for a complete check of his oral mucosa every 3 months from now on.
People with the RTEL1 mutation are also at an extremely high risk of blood cancers, particularly Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). As with Peter's overall bone marrow failure (which remains remarkably stable), the only treatment for MDS and AML is bone marrow transplant. I shared with the team our decision NOT to put Peter through a transplant given all his issues. They were very sympathetic and respectful, and emphasized that (as I had guessed) it would be highly unlikely for us to find a suitable donor for Peter anyway.
As I've mentioned before, Peter's telomeres (chemical "caps" on the DNA strands that help to maintain genetic stability as cells divide) are extraordinarily short. All people with Dyskeratosis Congenita have short telomeres, but his are among the very shortest they have seen. Our telomeres are at their longest when we are born, and they get shorter and shorter as we age. Peter's telomeres are like those of a 100-year-old person. This means he is extremely genetically unstable, a real ticking time bomb. He really should have been much sicker already.
It turns out that his Dyskeratosis Congenita (DC) is only one piece of his genetic puzzle. He has 2 or 3 other very significant mutations that will be studied, in time, by other geneticists at NIH. It's quite possible that these mutations haven't been seen before, so identifying them probably won't tell us anything. The geneticists at NIH feel that the totality of Peter's physical anomalies represent more than just the RTEL1 mutation. In other words, he has a lot going on due to his consanguinous parentage (incest between mother and father). It's even possible that one of the other mutations is somehow ameliorating the impact of the RTEL1 mutation, resulting in the unusual stability we've been seeing.
One thing we learned from our visit was that Peter has pretty severe osteoporosis from his total lack of testosterone. We decided not to give him a testosterone patch to induce puberty because he was resistant to the idea and -- more importantly -- his psychiatrist predicted that it would de-stabilize him in a most unpleasant way. The NIH doctors would like us to try a tiny piece of a patch to give him at least a little testosterone, because his osteoporosis is progressing quickly. We're not sure what to do, but will talk it over with his endocrinologist.
It was good to hear that we've been doing some things right. Peter's diabetes is very well controlled for his age, as is his hypothyroidism. He's been having his eyes examined regularly for diabetic retinopathy. We've treated his mood disorder as effectively as it can be treated. For a kid with his IQ, he is very functional and independent. Moreover, he doesn't live his life as a sick person. He doesn't have limitations and we keep him away from doctors and hospitals so he can just live his life.
When I talk about the stability of Peter's bone marrow failure, I mean that he has remained in essentially the same place for most of the past 8 years: modestly low white count and hemoglobin, and extremely low platelets (35-45). We had expected his immune function to decline and his anemia to get much worse by now, but it hasn't happened so far. Some parents would be all over their kids to avoid physical activity with platelets that low, for risk of bleeding. But we're not going to hover over him or wring our hands every time he leaves the house.
As we left the NIH, we had all of these results conveyed to us verbally and in a preliminary written report. The only thing we didn't know were the results of Peter's bone marrow biopsy on the next-to-last day. The last bone marrow biopsy was 5 years ago. If we were planning a bone marrow transplant we'd have been doing them every 6 months since then, but it's a major procedure with anesthesia and an incision where they punch through the hip to extract the marrow, and we're NOT planning a transplant. I was, understandably, very curious about how his bone marrow looks now.
Previously, Peter's marrow was found to be 5% cellular (95% empty). The team at NIH told me that this number could vary quite a bit depending on the specific spot where the cells were extracted. Bone marrow is not uniform. I had been wondering how he could be so stable with 95% of his bone marrow gone, but they said there were probably other places where the marrow had more cells and was working hard to keep his blood counts where they were. This time, his cellularity was measured at 20%, which is good news, so to speak.
On the other hand ...
Peter's bone marrow cells are no longer just sparse, but also abnormal. The abnormalities occur on all three lines: white cells, red cells and platelets. They took a sample of 20 cells and did a chromosome analysis on them to see if they showed mutations (evidence of genetic instability). 19 of the 20 were mutants with one arm of chromosome 7 broken off and joined to chromosome 1. Based on these results, it is clear that he now has intermediate-stage Myelodysplastic Syndrome, which as I mentioned earlier is a blood cancer.
The bone marrow failure study team has passed Peter's marrow over to the MDS experts at NIH to see if they can give us any further information. In the meantime, I did a deep dive in the literature and used the sophisticated life expectancy calculator on the MDS Association website to arrive at some prognostic information. As things are today, Peter's median life expectancy is 3 years, and he has a 44% chance of surviving 5 years. His chance of evolving from MDS to AML is about 60%. If that evolution happens, the median time for it to start happening is about 12 months.
When MDS turns into AML, it can happen in a matter of days, or it can take a few weeks or even a few months to go from initial signs to acute illness. The signs are exhaustion, weight loss, fever, loss of appetite. If the MDS doesn't turn to AML, then his blood counts will start to decline faster, and he will start to get infections, or need transfusions, or have bleeds due to his low platelets.
Back when Peter was first diagnosed, we thought he had a matter of months to live. But then he remained stable for a long, long time. Although I've been living with a grand piano over my head, the rope it's hanging on has been sturdy and I've learned to ignore it pretty well. Not that it's easy living with it, mind you. But what else can I do but live my life to the fullest and make sure that Peter lives his the same way? It's eventually going to fall, but it could be up there a long time.
Now the rope has clearly frayed and I am hearing tiny creaks from the piano. It will probably fall within the next 2-4 years, but it could fall much sooner. Or much later. It could creak and swing and scare us for weeks and months and years, or it could fall suddenly with no warning. For Peter's sake, I am hoping for the latter. I want him to be sick for the shortest possible time with the least amount of fear and suffering. I wish I could have some control over that, but alas, I cannot.
The Dyskeratosis Congenita group on Facebook is a great comfort to me, as are all the friends and family members who have been following Peter's journey with me. No parent should be in this position, knowing that her child's days are numbered and that she will have to walk with him fearlessly all the way to the end. And yet ... this is the path that lays before me.
Thank you for being here with me.
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