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Gene-Replacement Therapy for SMA1 May Necessitate New Rating Measures to Capture Patients’ Motor Function Gains
CHOP-INTEND scores plateaued in a phase I trial of AVXS-101 even as patients reached new motor milestones.
CHICAGO—The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was designed to track motor function in patients with spinal muscular atrophy type 1 (SMA1), but the test may not be sensitive to advances in motor function made by patients who receive an investigational gene-replacement therapy, researchers said at the 47th Annual Meeting of the Child Neurology Society.
AVXS-101 is an adeno-associated virus serotype 9 (AAV9)-based gene-replacement therapy that contains a copy of the SMN1 gene. AVXS-101 crosses the blood–brain barrier and is meant to treat the deletion or loss of function of the SMN1 gene in patients with SMA. The treatment may result in sustained SMN protein expression with a one-time dose.
Researchers conducted a phase I, open-label, dose-escalation study to study the treatment. Fifteen patients received AVXS-101 intravenously, and 12 participants received the proposed therapeutic dose.
“Patients treated with AVXS-101 achieved and maintained motor milestones unprecedented in the natural history of SMA1,” said Linda P. Lowes, PT, PhD, Principal Investigator for the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and Associate Professor of Pediatrics at Ohio State University, and colleagues. “CHOP-INTEND is a reliable tool for detecting early treatment impact, but appears insensitive to further motor function gains among AVXS-101–treated children as they age and develop.”
For example, the scale did not capture skills such as independent rolling and sitting that had not been seen in patients with SMA1, the researchers said.
CHOP-INTEND uses a 0–64-point scale where higher scores indicate better motor function. By six months, essentially no untreated patients with SMA1 achieve a score of 40 or greater points on the CHOP-INTEND, and scores may decrease between age 6 and 12 months. In the phase I trial of AVXS-101, CHOP-INTEND score increased from baseline by a mean of 9.8 points at one month postdose, 15.4 points at three months postdose, and 25.4 points at 24 months (n = 12 at all time points). Eleven of the 12 patients maintained a CHOP-INTEND score greater than 40 points for a mean of 19.5 months. Two children were able to crawl, pull to a stand, and stand and walk independently.
In the study, patients who achieved additional sitting milestones did not have accompanying increases on their CHOP-INTEND scores. For example, the 11 patients who sat for at least 5 seconds had a mean CHOP-INTEND plateau score of 56.9, while the 10 patients who sat for at least 10 seconds had a mean CHOP-INTEND plateau score of 57.0 and the nine patients who sat for at least 30 seconds had a mean CHOP-INTEND plateau score of 57.7.
The investigators suggested that the addition of scoring items such as supported sitting, head lifting, and walking could “mitigate the artificial ceiling effect” with the current scoring system. Other modifications to CHOP-INTEND, such as assessing one side of a patient instead of both sides, could reduce test administration time without affecting scores.
Furthermore, several CHOP-INTEND items may not perform well in assessing patients treated with AVXS-101 because they test primitive reflexes that fade as children live longer (eg, spinal incurvation) or children may become too heavy for the tests (eg, ventral suspension).
The study was sponsored by AveXis.
CHOP-INTEND scores plateaued in a phase I trial of AVXS-101 even as patients reached new motor milestones.
CHOP-INTEND scores plateaued in a phase I trial of AVXS-101 even as patients reached new motor milestones.
CHICAGO—The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was designed to track motor function in patients with spinal muscular atrophy type 1 (SMA1), but the test may not be sensitive to advances in motor function made by patients who receive an investigational gene-replacement therapy, researchers said at the 47th Annual Meeting of the Child Neurology Society.
AVXS-101 is an adeno-associated virus serotype 9 (AAV9)-based gene-replacement therapy that contains a copy of the SMN1 gene. AVXS-101 crosses the blood–brain barrier and is meant to treat the deletion or loss of function of the SMN1 gene in patients with SMA. The treatment may result in sustained SMN protein expression with a one-time dose.
Researchers conducted a phase I, open-label, dose-escalation study to study the treatment. Fifteen patients received AVXS-101 intravenously, and 12 participants received the proposed therapeutic dose.
“Patients treated with AVXS-101 achieved and maintained motor milestones unprecedented in the natural history of SMA1,” said Linda P. Lowes, PT, PhD, Principal Investigator for the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and Associate Professor of Pediatrics at Ohio State University, and colleagues. “CHOP-INTEND is a reliable tool for detecting early treatment impact, but appears insensitive to further motor function gains among AVXS-101–treated children as they age and develop.”
For example, the scale did not capture skills such as independent rolling and sitting that had not been seen in patients with SMA1, the researchers said.
CHOP-INTEND uses a 0–64-point scale where higher scores indicate better motor function. By six months, essentially no untreated patients with SMA1 achieve a score of 40 or greater points on the CHOP-INTEND, and scores may decrease between age 6 and 12 months. In the phase I trial of AVXS-101, CHOP-INTEND score increased from baseline by a mean of 9.8 points at one month postdose, 15.4 points at three months postdose, and 25.4 points at 24 months (n = 12 at all time points). Eleven of the 12 patients maintained a CHOP-INTEND score greater than 40 points for a mean of 19.5 months. Two children were able to crawl, pull to a stand, and stand and walk independently.
In the study, patients who achieved additional sitting milestones did not have accompanying increases on their CHOP-INTEND scores. For example, the 11 patients who sat for at least 5 seconds had a mean CHOP-INTEND plateau score of 56.9, while the 10 patients who sat for at least 10 seconds had a mean CHOP-INTEND plateau score of 57.0 and the nine patients who sat for at least 30 seconds had a mean CHOP-INTEND plateau score of 57.7.
The investigators suggested that the addition of scoring items such as supported sitting, head lifting, and walking could “mitigate the artificial ceiling effect” with the current scoring system. Other modifications to CHOP-INTEND, such as assessing one side of a patient instead of both sides, could reduce test administration time without affecting scores.
Furthermore, several CHOP-INTEND items may not perform well in assessing patients treated with AVXS-101 because they test primitive reflexes that fade as children live longer (eg, spinal incurvation) or children may become too heavy for the tests (eg, ventral suspension).
The study was sponsored by AveXis.
CHICAGO—The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was designed to track motor function in patients with spinal muscular atrophy type 1 (SMA1), but the test may not be sensitive to advances in motor function made by patients who receive an investigational gene-replacement therapy, researchers said at the 47th Annual Meeting of the Child Neurology Society.
AVXS-101 is an adeno-associated virus serotype 9 (AAV9)-based gene-replacement therapy that contains a copy of the SMN1 gene. AVXS-101 crosses the blood–brain barrier and is meant to treat the deletion or loss of function of the SMN1 gene in patients with SMA. The treatment may result in sustained SMN protein expression with a one-time dose.
Researchers conducted a phase I, open-label, dose-escalation study to study the treatment. Fifteen patients received AVXS-101 intravenously, and 12 participants received the proposed therapeutic dose.
“Patients treated with AVXS-101 achieved and maintained motor milestones unprecedented in the natural history of SMA1,” said Linda P. Lowes, PT, PhD, Principal Investigator for the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, and Associate Professor of Pediatrics at Ohio State University, and colleagues. “CHOP-INTEND is a reliable tool for detecting early treatment impact, but appears insensitive to further motor function gains among AVXS-101–treated children as they age and develop.”
For example, the scale did not capture skills such as independent rolling and sitting that had not been seen in patients with SMA1, the researchers said.
CHOP-INTEND uses a 0–64-point scale where higher scores indicate better motor function. By six months, essentially no untreated patients with SMA1 achieve a score of 40 or greater points on the CHOP-INTEND, and scores may decrease between age 6 and 12 months. In the phase I trial of AVXS-101, CHOP-INTEND score increased from baseline by a mean of 9.8 points at one month postdose, 15.4 points at three months postdose, and 25.4 points at 24 months (n = 12 at all time points). Eleven of the 12 patients maintained a CHOP-INTEND score greater than 40 points for a mean of 19.5 months. Two children were able to crawl, pull to a stand, and stand and walk independently.
In the study, patients who achieved additional sitting milestones did not have accompanying increases on their CHOP-INTEND scores. For example, the 11 patients who sat for at least 5 seconds had a mean CHOP-INTEND plateau score of 56.9, while the 10 patients who sat for at least 10 seconds had a mean CHOP-INTEND plateau score of 57.0 and the nine patients who sat for at least 30 seconds had a mean CHOP-INTEND plateau score of 57.7.
The investigators suggested that the addition of scoring items such as supported sitting, head lifting, and walking could “mitigate the artificial ceiling effect” with the current scoring system. Other modifications to CHOP-INTEND, such as assessing one side of a patient instead of both sides, could reduce test administration time without affecting scores.
Furthermore, several CHOP-INTEND items may not perform well in assessing patients treated with AVXS-101 because they test primitive reflexes that fade as children live longer (eg, spinal incurvation) or children may become too heavy for the tests (eg, ventral suspension).
The study was sponsored by AveXis.
Can ultrasound screening improve survival in ovarian cancer?
Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.
“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.
The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.
The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.
Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).
However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.
The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.
One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”
Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.
SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.
Use a measure of caution when interpreting the results of the study by van Nagell et al., Sharon E. Robertson, MD, MPH, and Jeffery E. Peipert, MD, PhD, said in an invited commentary. First, they noted the “surprisingly high” rate of ovarian cancer (271 per 100,000) – although it may improve the predictive value of ultrasound screening, when one applies the test sensitivity and specificity the trial reported to the general population, “the positive predictive value falls to an unacceptable 0.7%.”
They also questioned the rationale for comparing the study population to an unscreened cohort of women with ovarian cancer referred to the University of Kentucky. “However, are we really comparing apples to apples?” they asked, noting “important key baseline differences” between the two groups, including that the screened cohort “could have contained an unbalanced proportion of genetically related ovarian cancers.” They also noted the risk profile of the unscreened cohort is unknown.
Addressing the differences in survival rates between screened and unscreened patients, Dr. Robertson and Dr. Peipert noted the study population had a higher rate of type I tumors than that seen in National Cancer Institute data for the general population (27% vs. 11%), along with the absence of genetic analysis. “For these reasons, we cannot confidently agree with the authors’ conclusion that the ultrasound screening reduced ovarian cancer mortality,” they stated.
They commended the Kentucky group for a “landmark study,” but added, “the evidence that screening for ovarian cancer improves survival remains elusive.” They called for more evidence before widespread screening programs are implemented.
Dr. Robertson and Dr. Peipert of Indiana University, Indianapolis, commented on the article by van Nagell et al. in Obstetrics and Gynecology (2018 Nov;132[5]:1089-90. doi: 10.1097/AOG.0000000000002962). Dr. Peipert disclosed relationships with Cooper Surgical/Teva, Merck, and Bayer. Dr. Robertson had no relevant financial relationships.
Use a measure of caution when interpreting the results of the study by van Nagell et al., Sharon E. Robertson, MD, MPH, and Jeffery E. Peipert, MD, PhD, said in an invited commentary. First, they noted the “surprisingly high” rate of ovarian cancer (271 per 100,000) – although it may improve the predictive value of ultrasound screening, when one applies the test sensitivity and specificity the trial reported to the general population, “the positive predictive value falls to an unacceptable 0.7%.”
They also questioned the rationale for comparing the study population to an unscreened cohort of women with ovarian cancer referred to the University of Kentucky. “However, are we really comparing apples to apples?” they asked, noting “important key baseline differences” between the two groups, including that the screened cohort “could have contained an unbalanced proportion of genetically related ovarian cancers.” They also noted the risk profile of the unscreened cohort is unknown.
Addressing the differences in survival rates between screened and unscreened patients, Dr. Robertson and Dr. Peipert noted the study population had a higher rate of type I tumors than that seen in National Cancer Institute data for the general population (27% vs. 11%), along with the absence of genetic analysis. “For these reasons, we cannot confidently agree with the authors’ conclusion that the ultrasound screening reduced ovarian cancer mortality,” they stated.
They commended the Kentucky group for a “landmark study,” but added, “the evidence that screening for ovarian cancer improves survival remains elusive.” They called for more evidence before widespread screening programs are implemented.
Dr. Robertson and Dr. Peipert of Indiana University, Indianapolis, commented on the article by van Nagell et al. in Obstetrics and Gynecology (2018 Nov;132[5]:1089-90. doi: 10.1097/AOG.0000000000002962). Dr. Peipert disclosed relationships with Cooper Surgical/Teva, Merck, and Bayer. Dr. Robertson had no relevant financial relationships.
Use a measure of caution when interpreting the results of the study by van Nagell et al., Sharon E. Robertson, MD, MPH, and Jeffery E. Peipert, MD, PhD, said in an invited commentary. First, they noted the “surprisingly high” rate of ovarian cancer (271 per 100,000) – although it may improve the predictive value of ultrasound screening, when one applies the test sensitivity and specificity the trial reported to the general population, “the positive predictive value falls to an unacceptable 0.7%.”
They also questioned the rationale for comparing the study population to an unscreened cohort of women with ovarian cancer referred to the University of Kentucky. “However, are we really comparing apples to apples?” they asked, noting “important key baseline differences” between the two groups, including that the screened cohort “could have contained an unbalanced proportion of genetically related ovarian cancers.” They also noted the risk profile of the unscreened cohort is unknown.
Addressing the differences in survival rates between screened and unscreened patients, Dr. Robertson and Dr. Peipert noted the study population had a higher rate of type I tumors than that seen in National Cancer Institute data for the general population (27% vs. 11%), along with the absence of genetic analysis. “For these reasons, we cannot confidently agree with the authors’ conclusion that the ultrasound screening reduced ovarian cancer mortality,” they stated.
They commended the Kentucky group for a “landmark study,” but added, “the evidence that screening for ovarian cancer improves survival remains elusive.” They called for more evidence before widespread screening programs are implemented.
Dr. Robertson and Dr. Peipert of Indiana University, Indianapolis, commented on the article by van Nagell et al. in Obstetrics and Gynecology (2018 Nov;132[5]:1089-90. doi: 10.1097/AOG.0000000000002962). Dr. Peipert disclosed relationships with Cooper Surgical/Teva, Merck, and Bayer. Dr. Robertson had no relevant financial relationships.
Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.
“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.
The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.
The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.
Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).
However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.
The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.
One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”
Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.
SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.
Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.
“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.
The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.
The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.
Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).
However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.
The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.
One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”
Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.
SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: Annual ultrasound may improve outcomes for women at risk for epithelial ovarian cancer.
Major finding: Five-year survival was 86% for screened women vs. 45% for unscreened women (P less than .001).
Study details: Analysis of 46,101 at-risk women enrolled in the University of Kentucky Ovarian Cancer Screening Trial, a prospective cohort trial, from January 1987 to June 2017.
Disclosures: Dr. van Nagell and coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.
Source: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.
Expert Opinions: Considerations to Guide Conversion From Carbamazepine or Oxcarbazepine to Eslicarbazepine Acetate
Patients typically switch from carbamazepine (CBZ) or oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) for at least 1 of 3 reasons: tolerability, simpler dosing, and/or efficacy. Since no evidence-based recommendations exist regarding the switching schedule, expert opinions may prove helpful for practitioners. In this supplement, expert epileptologists and clinical trialists share their experience about switching patients from CBZ or OXC to ESL.
Supplement
Click here or on the image below to read the supplement
Podcasts
Dr. Elinor Ben-Menachem discusses the case of a 28-year-old man with focal onset epilepsy who was switched from CBZ to ESL.
Dr. Toufic Fakhoury discusses the case of a 34-year-old female who became seizure-free after switching from OXC to ESL.
Dr. Mohamad Koubeissi discusses the case of a 22-year-old man with intractable epilepsy who was switched from OXC to ESL.
Dr. John Stern discusses the case of a 48-year-woman with tonic-clonic seizures who was switched from CBZ to ESL.
Dr. James Wheless discusses the case of an 8-year-old male who found relief having switched from OXC to ESL.
About the Faculty
Professor of Neurology
Director, Epilepsy Center
George Washington University
Washington, DC
Professor
Institute of Neuroscience and Physiology
Department of Clinical Neurosciences
The Sahlgrenska Academy at the University of Gothenburg
Department of Neurology
Sahlgrenska University Hospital
Gothenburg, Sweden
Saint Joseph Health System
Lexington, KY
Professor, Department of Neurology
Director, Epilepsy Clinical Program
Director, Epilepsy Residency Training Program
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, CA
Professor and Chief, Department of Pediatric Neurology
Chair, Division of Pediatric Neurology
Director, Le Bonheur Comprehensive Epilepsy Program
Director, Le Bonheur Neuroscience Center
University of Tennessee Health Science Center
Memphis, TN
Patients typically switch from carbamazepine (CBZ) or oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) for at least 1 of 3 reasons: tolerability, simpler dosing, and/or efficacy. Since no evidence-based recommendations exist regarding the switching schedule, expert opinions may prove helpful for practitioners. In this supplement, expert epileptologists and clinical trialists share their experience about switching patients from CBZ or OXC to ESL.
Supplement
Click here or on the image below to read the supplement
Podcasts
Dr. Elinor Ben-Menachem discusses the case of a 28-year-old man with focal onset epilepsy who was switched from CBZ to ESL.
Dr. Toufic Fakhoury discusses the case of a 34-year-old female who became seizure-free after switching from OXC to ESL.
Dr. Mohamad Koubeissi discusses the case of a 22-year-old man with intractable epilepsy who was switched from OXC to ESL.
Dr. John Stern discusses the case of a 48-year-woman with tonic-clonic seizures who was switched from CBZ to ESL.
Dr. James Wheless discusses the case of an 8-year-old male who found relief having switched from OXC to ESL.
About the Faculty
Professor of Neurology
Director, Epilepsy Center
George Washington University
Washington, DC
Professor
Institute of Neuroscience and Physiology
Department of Clinical Neurosciences
The Sahlgrenska Academy at the University of Gothenburg
Department of Neurology
Sahlgrenska University Hospital
Gothenburg, Sweden
Saint Joseph Health System
Lexington, KY
Professor, Department of Neurology
Director, Epilepsy Clinical Program
Director, Epilepsy Residency Training Program
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, CA
Professor and Chief, Department of Pediatric Neurology
Chair, Division of Pediatric Neurology
Director, Le Bonheur Comprehensive Epilepsy Program
Director, Le Bonheur Neuroscience Center
University of Tennessee Health Science Center
Memphis, TN
Patients typically switch from carbamazepine (CBZ) or oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) for at least 1 of 3 reasons: tolerability, simpler dosing, and/or efficacy. Since no evidence-based recommendations exist regarding the switching schedule, expert opinions may prove helpful for practitioners. In this supplement, expert epileptologists and clinical trialists share their experience about switching patients from CBZ or OXC to ESL.
Supplement
Click here or on the image below to read the supplement
Podcasts
Dr. Elinor Ben-Menachem discusses the case of a 28-year-old man with focal onset epilepsy who was switched from CBZ to ESL.
Dr. Toufic Fakhoury discusses the case of a 34-year-old female who became seizure-free after switching from OXC to ESL.
Dr. Mohamad Koubeissi discusses the case of a 22-year-old man with intractable epilepsy who was switched from OXC to ESL.
Dr. John Stern discusses the case of a 48-year-woman with tonic-clonic seizures who was switched from CBZ to ESL.
Dr. James Wheless discusses the case of an 8-year-old male who found relief having switched from OXC to ESL.
About the Faculty
Professor of Neurology
Director, Epilepsy Center
George Washington University
Washington, DC
Professor
Institute of Neuroscience and Physiology
Department of Clinical Neurosciences
The Sahlgrenska Academy at the University of Gothenburg
Department of Neurology
Sahlgrenska University Hospital
Gothenburg, Sweden
Saint Joseph Health System
Lexington, KY
Professor, Department of Neurology
Director, Epilepsy Clinical Program
Director, Epilepsy Residency Training Program
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, CA
Professor and Chief, Department of Pediatric Neurology
Chair, Division of Pediatric Neurology
Director, Le Bonheur Comprehensive Epilepsy Program
Director, Le Bonheur Neuroscience Center
University of Tennessee Health Science Center
Memphis, TN
Carl C. Bell: Fetal alcohol spectrum disorder Part II
Glycemic effects of lorcaserin
Also today, increased risk for suicide among adults who harm themselves, banning corporal punishment may reduce violence in youth, and a formula that scores the quality of a diet is validated.
Also today, increased risk for suicide among adults who harm themselves, banning corporal punishment may reduce violence in youth, and a formula that scores the quality of a diet is validated.
Also today, increased risk for suicide among adults who harm themselves, banning corporal punishment may reduce violence in youth, and a formula that scores the quality of a diet is validated.
Obesity Rates Are Up From 2016
In 2017, 7 states reported an adult obesity prevalence at or above 35%, up from 5 states in 2016. In 2012, obesity prevalence was lower than 35% in all states. The new data, from the Behavioral Risk Factor Surveillance System, are detailed in the CDC’s 2017 Adult Obesity Prevalence Maps, www.cdc.gov/obesity/data/prevalence-maps.html.
The highest levels were in Alabama, Arkansas, Iowa, Louisiana, Mississippi, Oklahoma, and West Virginia. The lowest prevalence was 22.6% in Colorado. Adults aged 45 to54 years were twice as likely as young adults to report obesity (36% vs 17%). Non-Hispanic blacks had the highest prevalence (39%), followed by Hispanics (32.4%), and non-Hispanic whites (29.3%). When education was factored in, adults without a high school degree had the highest prevalence at 35.6%; high school graduates, 32.9%; adults with some college, 31.9%; and college graduates, 22.7%.
Maps showing obesity levels overall, as well as by race and ethnicity, are also available for 2011 through 2016.
In 2017, 7 states reported an adult obesity prevalence at or above 35%, up from 5 states in 2016. In 2012, obesity prevalence was lower than 35% in all states. The new data, from the Behavioral Risk Factor Surveillance System, are detailed in the CDC’s 2017 Adult Obesity Prevalence Maps, www.cdc.gov/obesity/data/prevalence-maps.html.
The highest levels were in Alabama, Arkansas, Iowa, Louisiana, Mississippi, Oklahoma, and West Virginia. The lowest prevalence was 22.6% in Colorado. Adults aged 45 to54 years were twice as likely as young adults to report obesity (36% vs 17%). Non-Hispanic blacks had the highest prevalence (39%), followed by Hispanics (32.4%), and non-Hispanic whites (29.3%). When education was factored in, adults without a high school degree had the highest prevalence at 35.6%; high school graduates, 32.9%; adults with some college, 31.9%; and college graduates, 22.7%.
Maps showing obesity levels overall, as well as by race and ethnicity, are also available for 2011 through 2016.
In 2017, 7 states reported an adult obesity prevalence at or above 35%, up from 5 states in 2016. In 2012, obesity prevalence was lower than 35% in all states. The new data, from the Behavioral Risk Factor Surveillance System, are detailed in the CDC’s 2017 Adult Obesity Prevalence Maps, www.cdc.gov/obesity/data/prevalence-maps.html.
The highest levels were in Alabama, Arkansas, Iowa, Louisiana, Mississippi, Oklahoma, and West Virginia. The lowest prevalence was 22.6% in Colorado. Adults aged 45 to54 years were twice as likely as young adults to report obesity (36% vs 17%). Non-Hispanic blacks had the highest prevalence (39%), followed by Hispanics (32.4%), and non-Hispanic whites (29.3%). When education was factored in, adults without a high school degree had the highest prevalence at 35.6%; high school graduates, 32.9%; adults with some college, 31.9%; and college graduates, 22.7%.
Maps showing obesity levels overall, as well as by race and ethnicity, are also available for 2011 through 2016.
Transfusion errors more common in kids than adults, study suggests
BOSTON—Even the most vigilant hospitals experience transfusion errors and problems with blood storage, according to researchers.
A review of data from 32 U.S. hospitals showed that pediatric transfusions were associated with a higher rate of safety problems than adult transfusions, with errors differing by age group.
The most common error in the pediatric population was failure to follow protocol, and the most common error in the adult population was that scheduled transfusions were not performed.
Sarah Vossoughi, MD, of Columbia University and New York–Presbyterian Hospital in New York, described these findings at AABB 2018 (abstract QT4).
To evaluate patient safety events related to blood transfusions, Dr. Vossoughi and her colleagues reviewed data on events reported by three children’s hospitals and 29 adult hospitals. Events were reported to either the AABB Center for Patient Safety or the medical center’s own adverse event reporting system from January 2010 through September 2017.
The researchers identified a total of 1,806 reports associated with approximately 1,088,884 transfusions.
There were 249 reports associated with 99,064 pediatric transfusions and 1,577 reports associated with 989,820 adult transfusions. So the reporting rate was 251 per 100,000 transfusions for the pediatric population and 157 per 100,000 transfusions for the adult population (P<0.001).
The most common error for pediatric patients—failure to follow the transfusion protocol—made up 31% of the pediatric errors.
“In a lot of the pediatric hospitals, it’s kind of like the Wild West,” Dr. Vossoughi said. “People say, ‘Well, I know it’s the hospital policy, but this child is special, so I’m going to do it this way, this time.’ That seems to be a culture in pediatrics, whereas, on the adult side, [clinicians] seem to be much less likely to just deviate from the protocol.”
Among adults, the most common error was “transfusion not performed,” which accounted for 43% of the adult errors. Dr. Vossoughi said transfusions may be skipped due to a bungled patient hand-off during a shift change or when a patient is being moved from one unit to another.
“The next day, they’ll check the patient’s CBC [complete blood count] and realize that the patient didn’t respond to the infusion that it turned out they never got, and then the product will be found on the floor, expired,” Dr. Vossoughi said.
She and her colleagues also found that 20% of pediatric errors and 24% of adult errors were associated with incorrect storage of blood products on the patient floor.
“It’s very common for blood banks to find platelets in the refrigerator,” Dr. Vossoughi said. “It doesn’t matter how old you are or what type of hospital you’re at. Everyone’s putting platelets in the fridge.”
Dr. Vossoughi and her colleagues believe these findings could help inpatient blood management programs target education and interventions to providers who commit similar errors.
“If you know that a particular provider group has problems following the protocol, maybe you can make the protocol a little simpler to follow or make the checklist less cumbersome, and then maybe they’ll follow them more often,” Dr. Vossoughi said.
This research was supported by the AABB Center for Patient Safety and University of Vermont Medical Center. The researchers reported no conflicts of interest.
BOSTON—Even the most vigilant hospitals experience transfusion errors and problems with blood storage, according to researchers.
A review of data from 32 U.S. hospitals showed that pediatric transfusions were associated with a higher rate of safety problems than adult transfusions, with errors differing by age group.
The most common error in the pediatric population was failure to follow protocol, and the most common error in the adult population was that scheduled transfusions were not performed.
Sarah Vossoughi, MD, of Columbia University and New York–Presbyterian Hospital in New York, described these findings at AABB 2018 (abstract QT4).
To evaluate patient safety events related to blood transfusions, Dr. Vossoughi and her colleagues reviewed data on events reported by three children’s hospitals and 29 adult hospitals. Events were reported to either the AABB Center for Patient Safety or the medical center’s own adverse event reporting system from January 2010 through September 2017.
The researchers identified a total of 1,806 reports associated with approximately 1,088,884 transfusions.
There were 249 reports associated with 99,064 pediatric transfusions and 1,577 reports associated with 989,820 adult transfusions. So the reporting rate was 251 per 100,000 transfusions for the pediatric population and 157 per 100,000 transfusions for the adult population (P<0.001).
The most common error for pediatric patients—failure to follow the transfusion protocol—made up 31% of the pediatric errors.
“In a lot of the pediatric hospitals, it’s kind of like the Wild West,” Dr. Vossoughi said. “People say, ‘Well, I know it’s the hospital policy, but this child is special, so I’m going to do it this way, this time.’ That seems to be a culture in pediatrics, whereas, on the adult side, [clinicians] seem to be much less likely to just deviate from the protocol.”
Among adults, the most common error was “transfusion not performed,” which accounted for 43% of the adult errors. Dr. Vossoughi said transfusions may be skipped due to a bungled patient hand-off during a shift change or when a patient is being moved from one unit to another.
“The next day, they’ll check the patient’s CBC [complete blood count] and realize that the patient didn’t respond to the infusion that it turned out they never got, and then the product will be found on the floor, expired,” Dr. Vossoughi said.
She and her colleagues also found that 20% of pediatric errors and 24% of adult errors were associated with incorrect storage of blood products on the patient floor.
“It’s very common for blood banks to find platelets in the refrigerator,” Dr. Vossoughi said. “It doesn’t matter how old you are or what type of hospital you’re at. Everyone’s putting platelets in the fridge.”
Dr. Vossoughi and her colleagues believe these findings could help inpatient blood management programs target education and interventions to providers who commit similar errors.
“If you know that a particular provider group has problems following the protocol, maybe you can make the protocol a little simpler to follow or make the checklist less cumbersome, and then maybe they’ll follow them more often,” Dr. Vossoughi said.
This research was supported by the AABB Center for Patient Safety and University of Vermont Medical Center. The researchers reported no conflicts of interest.
BOSTON—Even the most vigilant hospitals experience transfusion errors and problems with blood storage, according to researchers.
A review of data from 32 U.S. hospitals showed that pediatric transfusions were associated with a higher rate of safety problems than adult transfusions, with errors differing by age group.
The most common error in the pediatric population was failure to follow protocol, and the most common error in the adult population was that scheduled transfusions were not performed.
Sarah Vossoughi, MD, of Columbia University and New York–Presbyterian Hospital in New York, described these findings at AABB 2018 (abstract QT4).
To evaluate patient safety events related to blood transfusions, Dr. Vossoughi and her colleagues reviewed data on events reported by three children’s hospitals and 29 adult hospitals. Events were reported to either the AABB Center for Patient Safety or the medical center’s own adverse event reporting system from January 2010 through September 2017.
The researchers identified a total of 1,806 reports associated with approximately 1,088,884 transfusions.
There were 249 reports associated with 99,064 pediatric transfusions and 1,577 reports associated with 989,820 adult transfusions. So the reporting rate was 251 per 100,000 transfusions for the pediatric population and 157 per 100,000 transfusions for the adult population (P<0.001).
The most common error for pediatric patients—failure to follow the transfusion protocol—made up 31% of the pediatric errors.
“In a lot of the pediatric hospitals, it’s kind of like the Wild West,” Dr. Vossoughi said. “People say, ‘Well, I know it’s the hospital policy, but this child is special, so I’m going to do it this way, this time.’ That seems to be a culture in pediatrics, whereas, on the adult side, [clinicians] seem to be much less likely to just deviate from the protocol.”
Among adults, the most common error was “transfusion not performed,” which accounted for 43% of the adult errors. Dr. Vossoughi said transfusions may be skipped due to a bungled patient hand-off during a shift change or when a patient is being moved from one unit to another.
“The next day, they’ll check the patient’s CBC [complete blood count] and realize that the patient didn’t respond to the infusion that it turned out they never got, and then the product will be found on the floor, expired,” Dr. Vossoughi said.
She and her colleagues also found that 20% of pediatric errors and 24% of adult errors were associated with incorrect storage of blood products on the patient floor.
“It’s very common for blood banks to find platelets in the refrigerator,” Dr. Vossoughi said. “It doesn’t matter how old you are or what type of hospital you’re at. Everyone’s putting platelets in the fridge.”
Dr. Vossoughi and her colleagues believe these findings could help inpatient blood management programs target education and interventions to providers who commit similar errors.
“If you know that a particular provider group has problems following the protocol, maybe you can make the protocol a little simpler to follow or make the checklist less cumbersome, and then maybe they’ll follow them more often,” Dr. Vossoughi said.
This research was supported by the AABB Center for Patient Safety and University of Vermont Medical Center. The researchers reported no conflicts of interest.
Understanding the role of HSCT in PTCL
DUBROVNIK, CROATIA—Hematopoietic stem cell transplant (HSCT) can be hit-or-miss in patients with peripheral T-cell lymphomas (PTCLs), according to a speaker at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
Ali Bazarbachi, MD, PhD, of the American University of Beirut in Lebanon, noted that the success of HSCT varies according to the subtype of PTCL and the type of transplant.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with non-localized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Dr. Bazarbachi began his presentation by pointing out that patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable—localized ENKTL and ALK-positive ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
HSCT in PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 20121, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival—compared to previous results with CHOP2—in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma.
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients—those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study3 showed improved survival in patients who received consolidation with auto- or allo-HSCT, as compared to patients who did not receive a transplant.
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Dr. Bazarbachi noted that allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL.
However, chemosensitive patients who have relapsed should only receive auto-HSCT if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
HSCT in ATLL
Dr. Bazarbachi noted that ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative.4,5 It is most effective in patients who have achieved a complete or partial response to induction.
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time—as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 20145, all four ATLL patients who underwent auto-HSCT “rapidly” died.
HSCT in ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients6, and it is most effective when patients have achieved a complete response to induction.
Allo-HSCT is also an option for frontline consolidation in patients with non-localized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should only receive auto-HSCT if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, non-localized ENKTL, nasal type should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
He did not declare any conflicts of interest.
1. d’Amore F et al. J Clin Oncol. 2012 Sep 1;30(25):3093-9. doi: 10.1200/JCO.2011.40.2719
2. AbouYabis AN et al. ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924
3. Park SI et al. Blood 2017 130:342
4. Ishida T et al. Blood 2012 Aug 23;120(8):1734-41. doi: 10.1182/blood-2012-03-414490
5. Bazarbachi A et al. Bone Marrow Transplant. 2014 Oct;49(10):1266-8. doi: 10.1038/bmt.2014.143
6. Lee J et al. Biol Blood Marrow Transplant. 2008 Dec;14(12):1356-64. doi: 10.1016/j.bbmt.2008.09.014
DUBROVNIK, CROATIA—Hematopoietic stem cell transplant (HSCT) can be hit-or-miss in patients with peripheral T-cell lymphomas (PTCLs), according to a speaker at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
Ali Bazarbachi, MD, PhD, of the American University of Beirut in Lebanon, noted that the success of HSCT varies according to the subtype of PTCL and the type of transplant.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with non-localized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Dr. Bazarbachi began his presentation by pointing out that patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable—localized ENKTL and ALK-positive ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
HSCT in PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 20121, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival—compared to previous results with CHOP2—in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma.
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients—those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study3 showed improved survival in patients who received consolidation with auto- or allo-HSCT, as compared to patients who did not receive a transplant.
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Dr. Bazarbachi noted that allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL.
However, chemosensitive patients who have relapsed should only receive auto-HSCT if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
HSCT in ATLL
Dr. Bazarbachi noted that ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative.4,5 It is most effective in patients who have achieved a complete or partial response to induction.
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time—as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 20145, all four ATLL patients who underwent auto-HSCT “rapidly” died.
HSCT in ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients6, and it is most effective when patients have achieved a complete response to induction.
Allo-HSCT is also an option for frontline consolidation in patients with non-localized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should only receive auto-HSCT if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, non-localized ENKTL, nasal type should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
He did not declare any conflicts of interest.
1. d’Amore F et al. J Clin Oncol. 2012 Sep 1;30(25):3093-9. doi: 10.1200/JCO.2011.40.2719
2. AbouYabis AN et al. ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924
3. Park SI et al. Blood 2017 130:342
4. Ishida T et al. Blood 2012 Aug 23;120(8):1734-41. doi: 10.1182/blood-2012-03-414490
5. Bazarbachi A et al. Bone Marrow Transplant. 2014 Oct;49(10):1266-8. doi: 10.1038/bmt.2014.143
6. Lee J et al. Biol Blood Marrow Transplant. 2008 Dec;14(12):1356-64. doi: 10.1016/j.bbmt.2008.09.014
DUBROVNIK, CROATIA—Hematopoietic stem cell transplant (HSCT) can be hit-or-miss in patients with peripheral T-cell lymphomas (PTCLs), according to a speaker at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.
Ali Bazarbachi, MD, PhD, of the American University of Beirut in Lebanon, noted that the success of HSCT varies according to the subtype of PTCL and the type of transplant.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with non-localized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Dr. Bazarbachi began his presentation by pointing out that patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable—localized ENKTL and ALK-positive ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
HSCT in PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 20121, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival—compared to previous results with CHOP2—in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma.
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients—those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study3 showed improved survival in patients who received consolidation with auto- or allo-HSCT, as compared to patients who did not receive a transplant.
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Dr. Bazarbachi noted that allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL.
However, chemosensitive patients who have relapsed should only receive auto-HSCT if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
HSCT in ATLL
Dr. Bazarbachi noted that ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative.4,5 It is most effective in patients who have achieved a complete or partial response to induction.
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time—as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 20145, all four ATLL patients who underwent auto-HSCT “rapidly” died.
HSCT in ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients6, and it is most effective when patients have achieved a complete response to induction.
Allo-HSCT is also an option for frontline consolidation in patients with non-localized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should only receive auto-HSCT if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, non-localized ENKTL, nasal type should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
He did not declare any conflicts of interest.
1. d’Amore F et al. J Clin Oncol. 2012 Sep 1;30(25):3093-9. doi: 10.1200/JCO.2011.40.2719
2. AbouYabis AN et al. ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924
3. Park SI et al. Blood 2017 130:342
4. Ishida T et al. Blood 2012 Aug 23;120(8):1734-41. doi: 10.1182/blood-2012-03-414490
5. Bazarbachi A et al. Bone Marrow Transplant. 2014 Oct;49(10):1266-8. doi: 10.1038/bmt.2014.143
6. Lee J et al. Biol Blood Marrow Transplant. 2008 Dec;14(12):1356-64. doi: 10.1016/j.bbmt.2008.09.014
How Do I Use the New Cholesterol Guidelines?
Q) I’m still confused by the change in approach to use of statin therapy for cardiovascular disease. How do I determine which patients need statins?
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in adults in the United States.1 Statins have long been recommended in the management of individuals with ASCVD.
Historically, statin use was guided by an LDL cholesterol (LDL-C) target, per the Adult Treatment Panel (ATP III) guidelines. Therapy was intensified based on whether patients met these targets. Newer guidelines from the American Heart Association/American College of Cardiology (AHA/ACC) base statin therapy not on an LDL-C number but rather on risk stratification that considers several factors.1-3
Continue to: The AHA/ACC guidelines classify statins as...
The AHA/ACC guidelines classify statins as high-, moderate-, or low-intensity.2 They also identify four major groups in whom the benefits of statin therapy for reducing ASCVD risk outweigh the risks of therapy. These include patients with
- Clinical ASCVD (eg, coronary heart disease, stroke, transient ischemic attack, or atherosclerotic peripheral arterial disease)
- Primary elevated LDL-C ≥ 190 mg/dL
- Diabetes (specifically, in those ages 40-75 with an LDL-C of 70-189 mg/dL)
- An estimated 10-year ASCVD risk ≥ 7.5%.2,3 (A risk calculator can be found at www.cvriskcalculator.com).
Recommended statin regimens for patients meeting these criteria are outlined in the Table.
These new guidelines significantly increase the number of adults who are eligible for statin therapy. The number of adults ages 60 to 75 without cardiovascular disease who now qualify for statin therapy has substantially increased (from 30% to 87% in men and from 21% to 54% among women).4 The bulk of this increase is in adults needing primary prevention based on their 10-year cardiovascular risk.4 Evidence as to whether expanded use of statins will improve clinical outcomes is still pending. —AF
Ashley Fort
PA Program at Louisiana State University Health Science Center
1. Gencer B, Auer R, Nanchen D, et al. Expected impact of applying new 2013 AHA/ACC cholesterol guidelines criteria on the recommended lipid target achievement after acute coronary syndromes. Atherosclerosis. 2015; 239(1):118-124.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25):2889-2934.
3. Adhyaru B, Jacobson T. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia. Cardiol Clin. 2015;33(15):181-196.
4. Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422-1431.
Q) I’m still confused by the change in approach to use of statin therapy for cardiovascular disease. How do I determine which patients need statins?
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in adults in the United States.1 Statins have long been recommended in the management of individuals with ASCVD.
Historically, statin use was guided by an LDL cholesterol (LDL-C) target, per the Adult Treatment Panel (ATP III) guidelines. Therapy was intensified based on whether patients met these targets. Newer guidelines from the American Heart Association/American College of Cardiology (AHA/ACC) base statin therapy not on an LDL-C number but rather on risk stratification that considers several factors.1-3
Continue to: The AHA/ACC guidelines classify statins as...
The AHA/ACC guidelines classify statins as high-, moderate-, or low-intensity.2 They also identify four major groups in whom the benefits of statin therapy for reducing ASCVD risk outweigh the risks of therapy. These include patients with
- Clinical ASCVD (eg, coronary heart disease, stroke, transient ischemic attack, or atherosclerotic peripheral arterial disease)
- Primary elevated LDL-C ≥ 190 mg/dL
- Diabetes (specifically, in those ages 40-75 with an LDL-C of 70-189 mg/dL)
- An estimated 10-year ASCVD risk ≥ 7.5%.2,3 (A risk calculator can be found at www.cvriskcalculator.com).
Recommended statin regimens for patients meeting these criteria are outlined in the Table.
These new guidelines significantly increase the number of adults who are eligible for statin therapy. The number of adults ages 60 to 75 without cardiovascular disease who now qualify for statin therapy has substantially increased (from 30% to 87% in men and from 21% to 54% among women).4 The bulk of this increase is in adults needing primary prevention based on their 10-year cardiovascular risk.4 Evidence as to whether expanded use of statins will improve clinical outcomes is still pending. —AF
Ashley Fort
PA Program at Louisiana State University Health Science Center
Q) I’m still confused by the change in approach to use of statin therapy for cardiovascular disease. How do I determine which patients need statins?
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in adults in the United States.1 Statins have long been recommended in the management of individuals with ASCVD.
Historically, statin use was guided by an LDL cholesterol (LDL-C) target, per the Adult Treatment Panel (ATP III) guidelines. Therapy was intensified based on whether patients met these targets. Newer guidelines from the American Heart Association/American College of Cardiology (AHA/ACC) base statin therapy not on an LDL-C number but rather on risk stratification that considers several factors.1-3
Continue to: The AHA/ACC guidelines classify statins as...
The AHA/ACC guidelines classify statins as high-, moderate-, or low-intensity.2 They also identify four major groups in whom the benefits of statin therapy for reducing ASCVD risk outweigh the risks of therapy. These include patients with
- Clinical ASCVD (eg, coronary heart disease, stroke, transient ischemic attack, or atherosclerotic peripheral arterial disease)
- Primary elevated LDL-C ≥ 190 mg/dL
- Diabetes (specifically, in those ages 40-75 with an LDL-C of 70-189 mg/dL)
- An estimated 10-year ASCVD risk ≥ 7.5%.2,3 (A risk calculator can be found at www.cvriskcalculator.com).
Recommended statin regimens for patients meeting these criteria are outlined in the Table.
These new guidelines significantly increase the number of adults who are eligible for statin therapy. The number of adults ages 60 to 75 without cardiovascular disease who now qualify for statin therapy has substantially increased (from 30% to 87% in men and from 21% to 54% among women).4 The bulk of this increase is in adults needing primary prevention based on their 10-year cardiovascular risk.4 Evidence as to whether expanded use of statins will improve clinical outcomes is still pending. —AF
Ashley Fort
PA Program at Louisiana State University Health Science Center
1. Gencer B, Auer R, Nanchen D, et al. Expected impact of applying new 2013 AHA/ACC cholesterol guidelines criteria on the recommended lipid target achievement after acute coronary syndromes. Atherosclerosis. 2015; 239(1):118-124.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25):2889-2934.
3. Adhyaru B, Jacobson T. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia. Cardiol Clin. 2015;33(15):181-196.
4. Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422-1431.
1. Gencer B, Auer R, Nanchen D, et al. Expected impact of applying new 2013 AHA/ACC cholesterol guidelines criteria on the recommended lipid target achievement after acute coronary syndromes. Atherosclerosis. 2015; 239(1):118-124.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25):2889-2934.
3. Adhyaru B, Jacobson T. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia. Cardiol Clin. 2015;33(15):181-196.
4. Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422-1431.
Long-term follow-up results of ongoing trials highlighted at ACR 2018
A 5-year follow-up study comparing methods of meniscal tear management in patients with osteoarthritis kicks off the second Plenary Session on Monday, Oct. 22, at the annual meeting of the American College of Rheumatology.
Jeffrey N. Katz, MD, of Brigham and Women’s Hospital in Boston, and his colleagues conducted a long-term follow-up of patients from the METEOR study, the early results of which were presented at OARSI in 2017. Dr. Katz and his colleagues randomized patients with knee pain, meniscal tears, and OA changes on x-ray or MRI to physical therapy vs. physical therapy plus arthroscopic partial meniscectomy. After 5 years, pain relief was similar across treatment groups, supporting the short-term conclusion that these patients experience relief over time, irrespective of initial treatment. Overall, 25% of the patients had total knee replacement surgery during the follow-up period.
The session also includes a new presentation by Kenneth G. Saag, MD, of the University of Alabama at Birmingham of 2-year outcomes from a phase 3 trial of denosumab versus risedronate for glucocorticoid-induced osteoporosis that was first presented at EULAR this year.
At 2 years, denosumab proved superior for increasing spine and hip bone mineral density in osteoporosis patients, compared with risedronate, and demonstrated a similar safety profile.
In addition, attendees will hear updated long-term results from the SCOT trial of myeloablative autologous hematopoietic stem cell transplantation for scleroderma patients. Keith M. Sullivan, MD, of Duke University, Durham, N.C., and his colleagues found that the benefits of the treatment endured after 6-11 years, supporting results presented at ACR 2016.
A 5-year follow-up study comparing methods of meniscal tear management in patients with osteoarthritis kicks off the second Plenary Session on Monday, Oct. 22, at the annual meeting of the American College of Rheumatology.
Jeffrey N. Katz, MD, of Brigham and Women’s Hospital in Boston, and his colleagues conducted a long-term follow-up of patients from the METEOR study, the early results of which were presented at OARSI in 2017. Dr. Katz and his colleagues randomized patients with knee pain, meniscal tears, and OA changes on x-ray or MRI to physical therapy vs. physical therapy plus arthroscopic partial meniscectomy. After 5 years, pain relief was similar across treatment groups, supporting the short-term conclusion that these patients experience relief over time, irrespective of initial treatment. Overall, 25% of the patients had total knee replacement surgery during the follow-up period.
The session also includes a new presentation by Kenneth G. Saag, MD, of the University of Alabama at Birmingham of 2-year outcomes from a phase 3 trial of denosumab versus risedronate for glucocorticoid-induced osteoporosis that was first presented at EULAR this year.
At 2 years, denosumab proved superior for increasing spine and hip bone mineral density in osteoporosis patients, compared with risedronate, and demonstrated a similar safety profile.
In addition, attendees will hear updated long-term results from the SCOT trial of myeloablative autologous hematopoietic stem cell transplantation for scleroderma patients. Keith M. Sullivan, MD, of Duke University, Durham, N.C., and his colleagues found that the benefits of the treatment endured after 6-11 years, supporting results presented at ACR 2016.
A 5-year follow-up study comparing methods of meniscal tear management in patients with osteoarthritis kicks off the second Plenary Session on Monday, Oct. 22, at the annual meeting of the American College of Rheumatology.
Jeffrey N. Katz, MD, of Brigham and Women’s Hospital in Boston, and his colleagues conducted a long-term follow-up of patients from the METEOR study, the early results of which were presented at OARSI in 2017. Dr. Katz and his colleagues randomized patients with knee pain, meniscal tears, and OA changes on x-ray or MRI to physical therapy vs. physical therapy plus arthroscopic partial meniscectomy. After 5 years, pain relief was similar across treatment groups, supporting the short-term conclusion that these patients experience relief over time, irrespective of initial treatment. Overall, 25% of the patients had total knee replacement surgery during the follow-up period.
The session also includes a new presentation by Kenneth G. Saag, MD, of the University of Alabama at Birmingham of 2-year outcomes from a phase 3 trial of denosumab versus risedronate for glucocorticoid-induced osteoporosis that was first presented at EULAR this year.
At 2 years, denosumab proved superior for increasing spine and hip bone mineral density in osteoporosis patients, compared with risedronate, and demonstrated a similar safety profile.
In addition, attendees will hear updated long-term results from the SCOT trial of myeloablative autologous hematopoietic stem cell transplantation for scleroderma patients. Keith M. Sullivan, MD, of Duke University, Durham, N.C., and his colleagues found that the benefits of the treatment endured after 6-11 years, supporting results presented at ACR 2016.
REPORTING FROM THE ACR ANNUAL MEETING