See: https://ask.metafilter.com/251986/Do-doctors-actually-tell-their-patients-they-cannot-have-children
Monday, September 16, 2024
I never gave up hope or my faith
One day in August 2013, I was with friends as my children, Hudson, Lola, and Bella, then ages 3, 5, and 7, were having a play date. I started to not feel well and, when I went to the restroom, I noticed I had blood in my stool. I knew this wasn't normal, so I called my doctor and then headed to urgent care. I figured they would run some tests and maybe prescribe some medication and I told my husband, Scott, that I would be home shortly.
Then the lab test came back and the results showed a platelet count of 1,000. The typical number of platelets in the blood is usually 150,000 to 450,000, so my count was incredibly low. The doctor even repeated the test, assuming the equipment must have malfunctioned the first time. It had not.
Instead of going home with a prescription in hand, an ambulance took me to the hospital. I was admitted and ended up staying for about 43 days. After nearly a month and a half and countless tests, I was diagnosed with Stage II diffuse large B-cell non-Hodgkin lymphoma. I came to learn that this is a type of cancer that affects your white blood cells, or lymphocytes, and that it's particularly fast-moving and aggressive.
As you can imagine, I was scared. At 32 years old, I was a young mom with a wonderful husband and three beautiful children, with so much life left to live. A cancer diagnosis was the furthest thing from my mind. But, I came to find out that this cancer typically responds well to treatment, and my disease was caught in a relatively early stage, which would increase my chances for survival.
I began a standard protocol of chemotherapy. Halfway through treatment, a scan showed no tumors. I was ecstatic, but about seven months later, tests revealed that the cancer had returned. Next was a stem cell transplant, which was just the hardest treatment that you could ever imagine. But my body wasn't responding the way it should and the cancer was still there.
The transplant was unsuccessful. I was driving my kids in the car when I got the news from my doctor that my transplant had failed. It took everything in me to hold it together for them. When I got home, I lost it. I was completely heartbroken. I knew I was quickly running out of options.
At this point, my chances of survival were incredibly low. In fact, I was given only six months to live, but I didn't even know it. A doctor had shared that with my husband, but he didn't tell me because he wanted to protect me as best he could from the scary stuff while I focused on my treatment. He knew how important it was for me to continue to have hope. Sometimes, when you realize how dire things are, you do become hopeless, and it's so much harder to fight when you're hopeless.
When we finally met with my doctor, he told me that my only option left was a clinical trial. The challenge was that this clinical trial wasn't available in my home state of Kansas yet, and my doctor didn't know if I had enough time to even make it. You'd think that I would have been distressed by that news, but in that moment when faced with this life-or-death situation, all I felt was hope and faith instead of fear. I knew we would find a way.
This clinical trial, ZUMA-1 as it was called, was exploring an entirely new way of treating cancer in 2015 that the doctors told me was my best—and maybe only—chance for survival at that point. It was an immunotherapy called Chimeric Antigen Receptor T-cell therapy, or CAR T-cell therapy. This one-time therapy is designed to use my immune system to fight the cancer.
CAR T-cell therapy involves using your own T cells, a type of white blood cell, which were collected through a process called leukapheresis—blood withdrawal—and sent to a manufacturing facility where they add receptors to those T cells that match the protein on the cancer. These "supercharged" T cells are then infused into the body to fight the cancer.
My local hospital wasn't participating in this trial, so I had to travel to a hospital in Houston. I hopped on a plane to see if I qualified for this trial. I was a perfect fit and was quickly enrolled.
Nearly two years after my cancer journey had begun, I became just the third person in the world to take part in the clinical trial. ultimately this treatment developed by Kite Pharma became the first CAR T-cell therapy approved by the U.S. Food and Drug Administration in 2017 to treat the type of cancer that I had. By participating in the clinical trial, I helped pave the way for thousands of blood cancer patients like me who have been successfully treated since.
Within a month, scans showed that the cancer was gone. The same thing at 18 months. And now, nine years later, I'm still cancer-free. I never gave up hope or my faith, both in God and in the incredible doctors who were treating me. I'm grateful to be a survivor and for the opportunity to be a part of something as revolutionary as CAR T-cell therapy.
I truly feel that I'm here for a reason, that it wasn't my time to go. I believe that there were things that I was meant to accomplish, and I feel a responsibility to use my experience to help others.
I've been actively involved with the Leukemia and Lymphoma Society, as have my children who grew up with their mom fighting this battle. Over the years, we've helped to raise more than $200,000 for research. I never imagined that I could be passionate about something like this, but I just feel like that was part of what I was called to do in order to give back.
Today, I'm healthy and Scott and I are happier than we've ever been. Our children are now 18, 16, and 14. Bella just started college, Lola is playing on her high school golf team, and Hudson wants to be an oncologist. I think back on the years dealing with my cancer and just trying to survive, and I feel like I missed a really special time in my family's life. That makes me appreciate the time we have now even more.
I remember thinking that I could never imagine being normal and healthy again, and that I'd never be able to get back to a normal routine. I now know that my life isn't completely the same and I've changed as a person because of this experience. People often ask me about it, and I tell them I wouldn't take it back or go back in time and not have cancer, which may seem shocking. But it helped me look at life differently and I've grown—we've all grown—so much because of that and I would never want to take that away.
Emily Dumler was diagnosed with stage II diffused large B-cell non-Hodgkin lymphoma at the age of 32 in 2013 and given six months to live. With no other approved treatment options available, Emily was brave enough to try CAR T-cell therapy that was in clinical trial stages at the time. Within a month of the trial, Emily was declared cancer-free and remains so to this day. CAR T-cell therapy is now an approved treatment.
https://www.newsweek.com/i-was-given-six-months-live-wasnt-told-1948620
Then the lab test came back and the results showed a platelet count of 1,000. The typical number of platelets in the blood is usually 150,000 to 450,000, so my count was incredibly low. The doctor even repeated the test, assuming the equipment must have malfunctioned the first time. It had not.
Instead of going home with a prescription in hand, an ambulance took me to the hospital. I was admitted and ended up staying for about 43 days. After nearly a month and a half and countless tests, I was diagnosed with Stage II diffuse large B-cell non-Hodgkin lymphoma. I came to learn that this is a type of cancer that affects your white blood cells, or lymphocytes, and that it's particularly fast-moving and aggressive.
As you can imagine, I was scared. At 32 years old, I was a young mom with a wonderful husband and three beautiful children, with so much life left to live. A cancer diagnosis was the furthest thing from my mind. But, I came to find out that this cancer typically responds well to treatment, and my disease was caught in a relatively early stage, which would increase my chances for survival.
I began a standard protocol of chemotherapy. Halfway through treatment, a scan showed no tumors. I was ecstatic, but about seven months later, tests revealed that the cancer had returned. Next was a stem cell transplant, which was just the hardest treatment that you could ever imagine. But my body wasn't responding the way it should and the cancer was still there.
The transplant was unsuccessful. I was driving my kids in the car when I got the news from my doctor that my transplant had failed. It took everything in me to hold it together for them. When I got home, I lost it. I was completely heartbroken. I knew I was quickly running out of options.
At this point, my chances of survival were incredibly low. In fact, I was given only six months to live, but I didn't even know it. A doctor had shared that with my husband, but he didn't tell me because he wanted to protect me as best he could from the scary stuff while I focused on my treatment. He knew how important it was for me to continue to have hope. Sometimes, when you realize how dire things are, you do become hopeless, and it's so much harder to fight when you're hopeless.
When we finally met with my doctor, he told me that my only option left was a clinical trial. The challenge was that this clinical trial wasn't available in my home state of Kansas yet, and my doctor didn't know if I had enough time to even make it. You'd think that I would have been distressed by that news, but in that moment when faced with this life-or-death situation, all I felt was hope and faith instead of fear. I knew we would find a way.
This clinical trial, ZUMA-1 as it was called, was exploring an entirely new way of treating cancer in 2015 that the doctors told me was my best—and maybe only—chance for survival at that point. It was an immunotherapy called Chimeric Antigen Receptor T-cell therapy, or CAR T-cell therapy. This one-time therapy is designed to use my immune system to fight the cancer.
CAR T-cell therapy involves using your own T cells, a type of white blood cell, which were collected through a process called leukapheresis—blood withdrawal—and sent to a manufacturing facility where they add receptors to those T cells that match the protein on the cancer. These "supercharged" T cells are then infused into the body to fight the cancer.
My local hospital wasn't participating in this trial, so I had to travel to a hospital in Houston. I hopped on a plane to see if I qualified for this trial. I was a perfect fit and was quickly enrolled.
Nearly two years after my cancer journey had begun, I became just the third person in the world to take part in the clinical trial. ultimately this treatment developed by Kite Pharma became the first CAR T-cell therapy approved by the U.S. Food and Drug Administration in 2017 to treat the type of cancer that I had. By participating in the clinical trial, I helped pave the way for thousands of blood cancer patients like me who have been successfully treated since.
Within a month, scans showed that the cancer was gone. The same thing at 18 months. And now, nine years later, I'm still cancer-free. I never gave up hope or my faith, both in God and in the incredible doctors who were treating me. I'm grateful to be a survivor and for the opportunity to be a part of something as revolutionary as CAR T-cell therapy.
I truly feel that I'm here for a reason, that it wasn't my time to go. I believe that there were things that I was meant to accomplish, and I feel a responsibility to use my experience to help others.
I've been actively involved with the Leukemia and Lymphoma Society, as have my children who grew up with their mom fighting this battle. Over the years, we've helped to raise more than $200,000 for research. I never imagined that I could be passionate about something like this, but I just feel like that was part of what I was called to do in order to give back.
Today, I'm healthy and Scott and I are happier than we've ever been. Our children are now 18, 16, and 14. Bella just started college, Lola is playing on her high school golf team, and Hudson wants to be an oncologist. I think back on the years dealing with my cancer and just trying to survive, and I feel like I missed a really special time in my family's life. That makes me appreciate the time we have now even more.
I remember thinking that I could never imagine being normal and healthy again, and that I'd never be able to get back to a normal routine. I now know that my life isn't completely the same and I've changed as a person because of this experience. People often ask me about it, and I tell them I wouldn't take it back or go back in time and not have cancer, which may seem shocking. But it helped me look at life differently and I've grown—we've all grown—so much because of that and I would never want to take that away.
Emily Dumler was diagnosed with stage II diffused large B-cell non-Hodgkin lymphoma at the age of 32 in 2013 and given six months to live. With no other approved treatment options available, Emily was brave enough to try CAR T-cell therapy that was in clinical trial stages at the time. Within a month of the trial, Emily was declared cancer-free and remains so to this day. CAR T-cell therapy is now an approved treatment.
https://www.newsweek.com/i-was-given-six-months-live-wasnt-told-1948620
Sunday, September 15, 2024
Diffuse intrinsic pontine glioma 5
The family of an 11-year-old with an inoperable brain tumor are preparing for their last Christmas together after he was given six months to live -- just two weeks ago.
Reece Probert seemed perfectly healthy just last month, but his mom Jenna, 31, took him to the doctors when he suddenly developed a limp and then a slur.
Scans revealed he had a rare aggressive inoperable brain tumor which sufferers usually succumb to between six and 12 months after diagnosis.
His devastated family are rallying around to give him the best Christmas ever.
"It will be our last Christmas together and we want to make sure it's nice and comfortable and cozy for Reece," Jenna Probert, of Wombourne, South Staffordshire, said. "I want to make him feel like a king. He should feel like the most important person in the world. It will be emotional because it will be his last Christmas."
"We will decorate the whole house and make it look like Santa's grotto. It will be the most memorable Christmas ever," she said. "Reece knows he has cancer but doesn't know the reality of it. I can't face telling him. I just need him to be happy. Christmas will be a family day and we will give him anything he wants. We will just cherish it together as a family."
Reece Probert seemed perfectly healthy just last month, but his mom Jenna, 31, took him to the doctors when he suddenly developed a limp and then a slur.
Scans revealed he had a rare aggressive inoperable brain tumor which sufferers usually succumb to between six and 12 months after diagnosis.
His devastated family are rallying around to give him the best Christmas ever.
"It will be our last Christmas together and we want to make sure it's nice and comfortable and cozy for Reece," Jenna Probert, of Wombourne, South Staffordshire, said. "I want to make him feel like a king. He should feel like the most important person in the world. It will be emotional because it will be his last Christmas."
"We will decorate the whole house and make it look like Santa's grotto. It will be the most memorable Christmas ever," she said. "Reece knows he has cancer but doesn't know the reality of it. I can't face telling him. I just need him to be happy. Christmas will be a family day and we will give him anything he wants. We will just cherish it together as a family."
Reece Probert seemed perfectly healthy just last month, but his mom took him to the doctors when he suddenly developed a limp and then a slur.
Just six weeks ago, Reece was fit and healthy, but after returning from a trip to see his grandparents in Northern Ireland in November, his mom noticed unusual symptoms.
He had a limp and a sore hand, so his doctor sent him to the hospital for an X-ray, and for tests on his tendons.
But Probert really began to worry when Reece began to slur his words two weeks ago.
A neighbor, who had been diagnosed a benign brain tumor, noticed Reece struggling to speak and feared the worst, having suffered similar symptoms in the past.
Probert, a personal trainer, phoned 111 and was advised to take her son to the Russell's Hall Hospital, in Dudley, where doctors initially thought he had suffered a stroke.
But on Dec. 1, doctors at Birmingham Children's Hospital performed a CT scan and found an "abnormality" of the brain.
Two days later Probert was told her son had diffuse intrinsic pontine glioma (DIPG) - an aggressive cancer typically found in children.
"I collapsed when I was told that," she said. "I felt like my heart had been ripped out. It was a horrible feeling. They put him on steroids to reduce the swelling before he had the MRI scan."
"It was bad enough being told he had a stroke," she siad. "I was just praying that they had got it all wrong. I just started screaming 'no, no, no'. I couldn't breathe. It's the worst thing any mom can be told."
"Even the oncologist has tears in her eyes whilst she was telling me," Probert said. "We were taken into the family room and told that chemotherapy won't work and radiotherapy will only shrink the tumor. But it will come back and will eventually end his life."
"Most children die between six and 12 months from diagnosis," she said.
Reece is due to start his first round of radiotherapy to reduce the size of the tumor and give him more time.
Probert is now focused on making sure Reece has the most "amazing Christmas" with her, partner Robert Perry, 27, and his sister Trinity Alcock, 6.
"I've had to put the reality of it to the back of my mind," Probert said. "I'm just focused on enjoying him whilst we still have him. We want to make memories with him and just want to make sure he is happy and comfortable."
"Reece has been fantastic. He has taken it all in his stride and has been amazing," she said. "I couldn't be more proud of him. He is known as the class clown and his friends have been to visit him. For us, the next year is all about making him feel extra special."
Friends and family have launched fundraising campaigns and arranged charity events in a bid to raise money to ensure Reece has a Christmas to remember.
https://www.foxnews.com/health/boy-given-months-to-live-after-limp-led-to-terminal-brain-tumor-diagnosis
Just six weeks ago, Reece was fit and healthy, but after returning from a trip to see his grandparents in Northern Ireland in November, his mom noticed unusual symptoms.
He had a limp and a sore hand, so his doctor sent him to the hospital for an X-ray, and for tests on his tendons.
But Probert really began to worry when Reece began to slur his words two weeks ago.
A neighbor, who had been diagnosed a benign brain tumor, noticed Reece struggling to speak and feared the worst, having suffered similar symptoms in the past.
Probert, a personal trainer, phoned 111 and was advised to take her son to the Russell's Hall Hospital, in Dudley, where doctors initially thought he had suffered a stroke.
But on Dec. 1, doctors at Birmingham Children's Hospital performed a CT scan and found an "abnormality" of the brain.
Two days later Probert was told her son had diffuse intrinsic pontine glioma (DIPG) - an aggressive cancer typically found in children.
"I collapsed when I was told that," she said. "I felt like my heart had been ripped out. It was a horrible feeling. They put him on steroids to reduce the swelling before he had the MRI scan."
"It was bad enough being told he had a stroke," she siad. "I was just praying that they had got it all wrong. I just started screaming 'no, no, no'. I couldn't breathe. It's the worst thing any mom can be told."
"Even the oncologist has tears in her eyes whilst she was telling me," Probert said. "We were taken into the family room and told that chemotherapy won't work and radiotherapy will only shrink the tumor. But it will come back and will eventually end his life."
"Most children die between six and 12 months from diagnosis," she said.
Reece is due to start his first round of radiotherapy to reduce the size of the tumor and give him more time.
Probert is now focused on making sure Reece has the most "amazing Christmas" with her, partner Robert Perry, 27, and his sister Trinity Alcock, 6.
"I've had to put the reality of it to the back of my mind," Probert said. "I'm just focused on enjoying him whilst we still have him. We want to make memories with him and just want to make sure he is happy and comfortable."
"Reece has been fantastic. He has taken it all in his stride and has been amazing," she said. "I couldn't be more proud of him. He is known as the class clown and his friends have been to visit him. For us, the next year is all about making him feel extra special."
Friends and family have launched fundraising campaigns and arranged charity events in a bid to raise money to ensure Reece has a Christmas to remember.
https://www.foxnews.com/health/boy-given-months-to-live-after-limp-led-to-terminal-brain-tumor-diagnosis
3-methylcrotonyl-CoA carboxylase deficiency
Inspired by a patient identified on newborn screening
Abstract
3-methylcrotonyl-CoA carboxylase deficiency (3MCCD) is a hereditary disorder of leucine catabolism caused by pathogenetic variants in the MCCC1 or MCCC2 genes. Typically diagnosed through newborn screening (NBS), 3MCCD is characterized by elevation of 3-hydroxyisovalerylcarnitine (C5OH) in blood as well as increased excretion of 3-methylcrotonylglycine (3-MCG) in urine. While most diagnosed children remain asymptomatic, data on adults are scarce. To date, only 39 molecularly confirmed adult individuals have been reported, all being mothers diagnosed subsequent to their child NBS results. Herein, we present a 36-year-old asymptomatic man who was incidentally diagnosed with 3MCCD following his son NBS recall. Molecular analysis revealed compound heterozygosity for two pathogenic variants in the MCCC1 gene. This is the first molecularly confirmed adult man with 3MCCD reported. This case highlights the need for additional longitudinal follow-up data on individuals with 3MCCD to clarify the clinical significance of this condition and guide clinical practice, including NBS strategy.
Lin W, Wang K, Chen Y, Zheng Z, Lin Y. Newborn screening and genetic diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency in Quanzhou,China. Mol Genet Metab Rep. 2024 Aug 2;40:101127. doi: 10.1016/j.ymgmr.2024.101127. PMID: 39188588; PMCID: PMC11345313.
Abstract
Background and aims: 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is an autosomal recessive leucine catabolism condition caused by 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency due to MCCC1/MCCC2 variants. We investigated its incidence and features in Quanzhou, China.
Materials and methods: We screened 643,606 newborns (January 2014 to December 2022) for elevated 3-hydroxyisovalerylcarnitine (C5OH) levels using tandem mass spectrometry (MS/MS). Molecular analyses identified MCCC1/MCCC2 variants in suspected 3-MCCD cases.
Results: Seventeen neonates, two maternal patients, and one paternal patient had 3-MCCD. Its incidence in the Quanzhou study population was 1/37,859 newborns. All patients and neonates with 3-MCCD exhibited increased C5OH concentrations. Most patients [76.5%(13/17)] had increased urinary 3-methylcrotonylglycine (3-MCG) and 3-hydroxyisovaleric acid (3-HIVA) levels. Eight neonates and all adults with 3-MCCD had secondary carnitine deficiency. We identified seventeen variants, including 6 novel ones.MCCC1and MCCC2 variants were found in 47.1% and 52.9% of patients,with c.1331G > A (31.3%) and c.351_353delTGG (50.0%) being the most prevalent, respectively. Clinical symptoms were observed in 11.8% of patients.
Conclusion: We identified six new MCCC1/MCCC2 variants, enhancing our understanding of the 3-MCCD molecular profile. Secondary carnitine deficiency occurred in eight neonates and all adult patients. Although clinical symptoms were observed in 11.8% of patients, whether they were related to 3-MCCD remain unclear. Therefore, further studies are required to decide whether 3-MCCD and C5OH indicators should continue to be used.
Jagadish A, Sclater K, Lapinski T, Adkins K, Selzer L. A Unique Presentation of 3-Methylcrotonyl-CoA Carboxylase Deficiency. Cureus. 2023 May 23;15(5):e39401. doi: 10.7759/cureus.39401. PMID: 37362523; PMCID: PMC10287026.
Abstract
3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder resulting in impaired leucine metabolism. The condition is typically diagnosed with newborn screening; patients diagnosed at a later stage generally present with symptoms including metabolic disturbances, seizures, failure to thrive, or delayed development. We present the case of a child diagnosed at 12 months of age who was noted to have recurrent viral infections and nonspecific gastrointestinal symptoms of vomiting, hematochezia, and gaseous distention of the abdomen. Newborn screening did not reveal any abnormalities. Evaluation for underlying immunodeficiency was unremarkable; genetic testing revealed bi-allelic mutations in MCCC2, a known association of 3-methylcrotonyl-CoA carboxylase deficiency. It is important to consider genetic disorders when evaluating patients even if the newborn screening is unremarkable.
Wang H, Liu S, Wang B, Yang Y, Yu B, Wang L, Wang T. 3-Methylcrotonyl-CoA carboxylase deficiency newborn screening in a population of 536,008: is routine screening necessary? J Pediatr Endocrinol Metab. 2019 Dec 18;32(12):1321-1326. doi: 10.1515/jpem-2018-0536. PMID: 31730530.
Abstract
Objective To evaluate whether 3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD) should be routinely screened in newborns. Methods Dried blood spots (DBS) were collected and analyzed by tandem mass spectrometry (TMS). Blood samples were collected from infants with positive 3-MCCD results. Targeted sequencing was performed using the extended panel for inherited metabolic diseases to detect 306 genes. The sequencing libraries were quantified and used for massively parallel sequencing on the Illumina HiSeq 2500 platform. Results A total of 536,008 infants underwent newborn screening (NBS) and 14 cases of 3-MCCD were diagnosed. The incidence of 3-MCCD in Jiangsu province was 1:38,286. During the last 3 years of follow-up, none of the subjects with 3-MCCD exhibited obvious clinical symptoms. Only two children had mild feeding difficulties and vomiting. Eleven patients had complex variants of the MCCC1 gene, and three patients had mutations in MCCC2. In total, 17 types of MCCC1 or MCCC2 variants were found, and c.639 + 2t > a was the most common mutation. Conclusions As far as the current results are concerned, 3-MCCD may be benign in Jiangsu province. However, additional investigations and a longer follow-up period are necessary to decide whether NBS of 3-MCCD is necessary or not.
Thursday, September 12, 2024
Mirdametinib in children and adults with neurofibromatosis type 1-associated symptomatic inoperable plexiform neurofibroma
Christopher L. Moertel, Angela C. Hirbe, Hans H. Shuhaiber, David Viskochil, Alpa Sidhu, Kevin J. Bielamowicz, Michael Weber, Jack Li, L. Mary Smith, Lauren Weintraub,
Rene Y. McNall-Knapp, Fouad M. Hajjar, Nicholas K. Foreman, Timothy R. Gershon, Dusica Babovic-Vuksanovic. ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma. Meeting Abstract: 2024 ASCO Annual Meeting I Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology May 29, 2024
Abstract
Background: PN in patients (pts) with NF1 can cause pain, disfigurement, impaired quality of life (QoL), and can undergo malignant transformation. ReNeu (NCT03962543), a multicenter, open-label, Phase 2b study, evaluated efficacy and safety of the highly selective, oral, investigational MEK1/2 inhibitor mirdametinib in adult (≥18 y) and pediatric (2-17 y) pts with inoperable NF1 PN causing significant morbidities. Methods: Mirdametinib was administered as a capsule or dispersible tablet (2 mg/m2 BID, max 4 mg BID) without regard to food in 3 wk on/1 wk off 28-d cycles. The primary endpoint was confirmed objective response rate (ORR; percentage of pts with MRI-assessed ≥20% reduction of target PN volume by blinded independent central review [BICR] within the 24-cycle treatment phase). The minimum clinically relevant ORR (null) was defined as 23% for adults and 20% for pediatrics. Ptscould continue treatment in an optional long-term follow-up (LTFU) phase. Additional key endpoints were duration of response (DoR), time to response (TTR), change from baseline (BL) in target PN volume, pain severity (Numerical Rating Scale-11 [NRS-11]), pain interference (Pain Interference Index [PII]), health-related (HR) QoL (PedsQL), and safety. Results: All114 pts (58 adult, 56 pediatric) received mirdametinib. As of the 20 Sept 2023 data cutoff (DCO), BICR-confirmed ORR during the treatment phase was 41% (95% CI, 29-55; P<.001 vs null) in adults and 52% (95% CI, 38-65; P<.001 vs null) in pediatric pts. Two adult pts and 1 pediatric pt also had a confirmed response in the ongoing LTFU. Median (min, max) target PN volumetric best response from BL was -41% (-90, 13) and -42% (-91, 48) in adult and pediatric pts, respectively. As of the DCO, median treatment duration was 22 mo for each cohort and median DoR was not reached. Median (range) TTR was 7.8 (4-19) mo in adult pts and 7.9 (4-19) mo in pediatric pts. Adult and pediatric pts had statistically significant improvements from BL to cycle 13 in NRS-11, PII, and key PedsQL measures. Most frequent (≥35% pts) treatment-emergent adverse events (TEAEs) were dermatitis acneiform, diarrhea, nausea, and vomiting in adults and diarrhea, dermatitis acneiform, and vomiting in pediatric pts. 16% and 25% of adult and pediatric pts, respectively, had grade ≥3 treatment-related AEs, and 22% and 9%, respectively, discontinued due to TEAEs. Conclusions: In ReNeu, the largest multicenter NF1 PN trial reported to date, mirdametinib demonstrated a statistically significant ORR by BICR, with deep and durable PN volume reductions, significant improvements in pain severity, pain interference, and HRQoL, and a manageable safety profile in both adults and children. Together with a dispersible tablet formulation, these results underscore mirdametinib’s potential to become an important new treatment option for NF1 PN pts across all ages.
Wednesday, September 11, 2024
ROHHAD syndrome
Mom of 2 Describes 'Purgatory' of Not Knowing How Long Her Boys Will Live: 'There Is No Roadmap' (Exclusive)
Mandie Moore's young sons have the same debilitating rare disease. In her own words, she explains how she dedicates every day to improving their quality of life
When Mandie Moore’s 8-year-old son Max complained that his legs hurt during short walks in spring 2020, she worried something was wrong. Soon he had trouble getting down the driveway of their Roswell, Georgia, home.
After two years of visiting doctors and traveling to hospitals around the country, he was diagnosed with ROHHAD syndrome, an ultra-rare disorder that affects the respiratory, nervous and endocrine systems, according to the the National Association for Rare Disorders. There are only about 200 cases reported in literature and clinically to date, says Max's pediatric pulmonologist Dr. Ajay Kasi at Children’s Healthcare of Atlanta.
ROHHAD stands for rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. It causes extreme weight gain, difficulty breathing and other endocrine issues. It also reduces a child's life expectancy — 50 to 60% of cases end in early death. “It's an extremely rare disease which can be easily missed,” Kasi tells PEOPLE.
As Mandie and her husband Devon were coming to terms with Max's diagnosis, their younger son, Chance, began showing familiar symptoms of the syndrome. In 2023, the family learned he had the same disease, for which there is no treatment and no cure.
Mandie sat down with PEOPLE to share how she copes while striving to make memories for her boys, who are now 12 and 9. This is her story:
When Max was first diagnosed, I let out the biggest exhale ever. We finally had a name for it. But then the doctors said, "This isn't like cancer, where we can give you a guidebook of what's going to happen. There is no roadmap."
Because so few kids have ROHHAD, we don't know what our future will be or when the kids will decline. It could be in a day, a year, in five years. That's the hardest thing — living in this state of limbo. It's almost like purgatory. You allow yourself to build a little more hope for the future, but you have to be cautious and realistic. We try to live in the moment and face things as they come up.
I think the kids feel it. Chance has been asking me a lot of questions: What does heaven look like? What happens when you die? The kids are pretty intuitive about how their body feels.
Quality of life is the biggest thing for our family. Making decisions to do a medical intervention, like inserting a tracheostomy [a procedure to help air and oxygen reach the lungs by creating an opening into the windpipe from outside the neck] was really hard, especially because the boys had lived their whole lives — I hate the word "normal" — but in a more typical way. So to say that they struggled is an understatement. Max asked me about the trach, "Will I die without it?" I said, "Yes, you probably will."
Max had a cardiac arrest after his trach was put in two years ago. I remember being in the pediatric ICU watching them do CPR, I was holding his feet, and we were screaming, "Please don't go. Please stay." But we were planning his funeral. We didn't know the answers to questions like, “Would he want to be an organ donor?” Because he was 10, and who knows that at 10 years old? But it's conversations that we've since had with both of them.
There's a small Facebook community that I belong to for ROHHAD parents, about 200 members. We lost a girl who was 9 a week ago. We lost a 12-year-old two months ago. It's constant loss. But there's a 27-year-old guy in Texas, he still lives at home. But that's really the only outlier. The rest of the stories involve a lot of loss during the teenage years.
Max has a great quality of life. He's very happy. That's all I want. I want him here and I want him happy. I don't really care what it looks like. Chance is getting there. Still, they both struggle with depression and anxiety at times. Grief shows up differently for everybody — I think I'm always going to be working through mine. But we're all in different stages and Chance is still having a harder time. He just did his Make-A-Wish trip, but it took several tries because he kept getting sicker.
For us, making memories has become really important. They're very intentional now. Whereas before they got sick, we took vacations, we did all the things that families do. Now, if Max wakes at 5 a.m. and says, "I want to go see the sunrise," we go outside — even if we want to stay in bed. Yesterday, he wanted to look at the cotton candy sky, so we did.
We give them as many experiences as we can. We went fishing in St. Augustine, Fla., and Chance caught a fish. I bought tickets to Ed Sheeran’s concert in May. We took the boys to Disney in December. If they say I want to do something, then we do it.
Right now, Max is doing well. It doesn't look good from other people's standards, but by our standards, he's good. But it changes so fast. As soon as you get one thing under control, there's something else, because ROHHAD affects the entire body. It’s constant whack-a-mole. You beat a problem down, you can exhale for a few minutes, and then something else pops up.
There’s this pressure to be super mom and to act like you're fine all the time, and you're not fine all the time. Nobody living like this is fine. I go to bed sad every night, and that's okay to say. I sit in the dark a lot and think about the things they will never get a chance to experience. And it's okay to have therapy and address your mental health and your family's mental health, because this isn't a normal life. Knowing there is an expiration date, but not knowing when it's going to be — that's not normal.
Max is happy with his life and I think that that's something that's given me perspective. He's been dealt a real crap hand, but to be able to find happiness in simple things, and to want to keep on living, and to keep on fighting, and keep on learning — he wants to be a marine biologist. Even though he's got a trach and can't go underwater, he has an innocence, and it's just lovely that he wants to go to college. He's got plans for himself.
Even with his struggles, Chance is our funny joke guy. He heals everything with humor. This ordeal is still a big change for him because he was super active, and super physical, and played sports and did all the things, and now it's a completely different life for him. But he just wants to make people smile. He wants to make people laugh. He, too, has plans. He hopes to be a police officer.
I had to give up my career as an ICU nurse practitioner. I stopped working when Max started getting sick. I quit right around the time of his cardiac arrest. If I hear "code blue", it brings back the trauma. It's not possible for me to do that anymore.
I’m in school studying to become a licensed clinical social worker. It's my way of healing. I want to be a therapist and work with kids and their families who have undergone medical trauma. One of the reasons I decided to go back to school is because I'm faced with the reality that one day, what has been my entire world, will no longer be.
I always tell people who are dealing with a rare disease: If you can't get out of bed for a day, let somebody else help you out. Give yourself grace — but always get back up.
https://people.com/mom-shares-how-she-copes-not-knowing-how-long-2-boys-will-live-exclusive-8703830
See: https://childnervoussystem.blogspot.com/2015/08/rohhad.html
Stevens-Johnson syndrome
At 8 years old, Paige LaCombe was diagnosed with a rare and life-threatening skin disease called Stevens-Johnson syndrome.
The now 19-year-old recalls her yearslong recovery journey at Shriners Children’s Hospital, where she underwent more than 20 surgeries
She is hoping her story helps raise awareness about the condition, which is caused by an allergic reaction to medication
Paige LaCombe had a typical childhood in Scott, Louisiana, where she enjoyed school and extracurricular activities like soccer and dance. But everything changed for her in the second grade.
At just 8 years old, Paige started a new medication to help with breakthrough seizures for epilepsy. An allergic reaction to the medication caused a rare and debilitating skin condition that left her hospitalized and fighting for her life.
It started on March 23, 2013, when Paige woke up her parents in the middle of the night complaining of a burning and tingling sensation.
“She kept saying that she felt like she had bugs crawling on her,” her mother, Renee LaCombe, 40, tells PEOPLE. “We flipped on the lights and that’s when we realized. She had puffy lips, her eyes were completely red, her face was swollen, and she was developing what looked like a rash. Plus, she was having a really high fever.”
“We saw her and immediately rushed her to the hospital. And that's when things just went completely south,” she says.
At the hospital, Paige was initially misdiagnosed with pink eye and strep throat. Her symptoms continued to worsen but doctors were unable to figure out what was wrong.
“It was silent from the doctors. That's when I kind of knew, oh, this is not good,” Paige, now 19, tells PEOPLE. “I vividly remember thinking, ‘Am I going to die?’ Because at this point I could see my skin starting to blister. It was so scary.”
“It progressed while she was in the ER really quickly where anybody would touch her, her skin would just literally fall off,” Renee explains. “Paige was burning from the inside out. It was something that was not physically seen so by the time her skin started sloughing, she was already having all those feelings on the inside.”
As doctors struggled to provide answers, Renee turned to her sister-in-law, a nurse in Texas. Renee sent her photos of Paige and details about her condition. After extensive research, her sister-in-law believed Paige might be suffering from a skin disease called Stevens-Johnson syndrome. She recommended the family visit Shriners Children’s Hospital Galveston in Texas.
Renee approached Paige’s doctors about the possibility, but they surprisingly “didn’t align” with the diagnosis. So after three days, she made the difficult decision to get Paige discharged and transferred to the renowned pediatric burn center.
“If we would’ve stayed at the local hospital, she would not be alive,” Renee says.
And immediately after arriving at Shriners, she got answers for her little girl.
Paige’s diagnosis of Stevens-Johnson syndrome was confirmed. SJS is a rare and serious skin disorder caused by an allergic reaction to a medication.
Symptoms include a fever, sore mouth and throat, fatigue, burning eyes, red or purple rashes and blisters on the skin. As these erosions (painful open wounds that look like burns) develop, the top layer of affected skin dies and starts to shed, according to the Cleveland Clinic. The erosions typically spread to the eyes, chest, mouth, nose, throat, urinary tract, and genitals.
Paige was later diagnosed with the most severe form of SJS, called toxic epidermal necrolysis (TEN), where at least 30% of the skin is affected. In her case, 80% of her body was experiencing these painful blisters. According to the National Institutes of Health, about 30% of people who develop TEN do not survive.
“I was a hot mess. I truly was,” Renee says of her daughter’s diagnosis. “The first thing that the physicians told us was, ‘This is not good, but we're going to try our best to do everything that we can.'
Paige admits that she was “completely out of it” due to the excruciating pain and doesn’t even remember the three-hour ambulance ride from the local hospital to Shriners. “I had no sign of relief at that point,” she says. “I blacked out for a long period of time.”
“I finally woke up after, I'm not even sure what number surgery, but I opened my eyes in a whole new environment,” she continues. “I saw my parents, saw the doctors, and looked down and saw myself gauzed up like a mummy. That was frightening but I thought, hey, I'm still alive.”
ter being admitted to Shriners, Paige began a seven-year recovery journey that included more than 20 surgeries. Those procedures consisted of extensive wound care including 10 skin grafts using pig skin. She also underwent 11 corneal grafts, which involved using placenta tissue and bolstering her eyes shut to prevent her from going blind.
Paige missed second grade entirely and spent third through ninth grades in and out of the hospital. Renee admits that she “still lives with the guilt today” that her daughter was suffering due to a single medication. She did everything she could to give Paige back the life she lost.
“I saw my daughter decline really, really bad where we weren't sure if she was going to make it. It was horrible. It was very overwhelming. It definitely felt like I was in Grey’s Anatomy with the amount of doctors making circles,” Renee recalls. “But I'm thankful that it was a one-stop shop at Shriners and they literally did everything that they could to ensure minimal effects once she left the hospital.”
“They were so encouraging and they helped me through everything,” Paige stresses. “Even though my darkest point in life was at Shriners, I think of Shriners like a second family. I felt taken care of. I felt loved because the staff truly worked together for the better good of the patient. I still view Shriners as not only my lifesaver but my second home.”
Paige has since made a remarkable recovery, saying that she’s “healed beautifully. But she’s still dealing with some lasting effects of TEN. She regularly sees an ophthalmologist to address damage to her eyes. The teen uses a daily steroid to treat the blood vessels and she wears a prosthetic device — “basically like glass contacts” — to keep her eyes hydrated, doing whatever’s necessary to mitigate the risk of her becoming blind.
Additionally, because of the scar tissue that has developed, doctors say they don't know if Paige will be able to have children.
“I’m blessed to be alive,” says Paige, now a patient ambassador for Shriners Hospital. “Some days I have bad days with my eyes, but I can't complain. I'm very thankful to be here today.”
“It's been a journey. Stevens-Johnson syndrome is horrendous and most don't survive from this,” her mother adds. “Poor thing, this child is a miracle. She’s been through hell and back. We're unsure of motherhood and we're unsure of her vision. But right now she's thriving. It's amazing how she finally turned the corner.”
Today, Paige is a sophomore at South Louisiana Community College pursuing a degree in business management and marketing. Calling herself a social butterfly, she’s excited to feel a “sense of normalcy” being around her peers without visiting doctors every other day.
Additionally, both Paige and Renee want her story to help raise awareness about SJS and TEN, telling PEOPLE that they’ve been able to connect with other families navigating the disease.
“I hope that people take the time to maybe learn and educate themselves before they take a medication to not end up in this position,” Paige says.
“Educate before you medicate,” Renee stresses. “Ask the questions with your doctors, educate yourself. Don't feel intimidated with physicians. Know more about what some risks to taking medications are. Every day, I beat myself up for not asking more. So I have tried my hardest to turn this negative event in Paige's life into something positive.”
https://people.com/teen-recalls-burning-from-the-inside-out-rare-disease-exclusive-8709725
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