WASHINGTON – Five-year follow-up data on the magnetic device approved for treating gastroesophageal reflux disease confirm its long-term safety and efficacy, Dr. Robert A. Ganz reported at the annual Digestive Disease Week.

Five years after device implantation, the proportion of patients experiencing moderate to severe regurgitation had dropped to about 1%, from almost 60% at baseline, and two-thirds of patients were not taking any proton pump inhibitors (PPIs), said Dr. Ganz, chief of gastroenterology at Abbott Northwestern Hospital, Minneapolis, and one of the study investigators. These were among the results of the study that evaluated the device, the LINX Reflux Management System. The device was approved by the Food and Drug Administration FDA) in 2012 and is for the treatment of people with GERD as defined by abnormal pH testing, who continue to have chronic GERD symptoms that persist despite maximum medical therapy for the treatment of reflux.

“Magnetic sphincter augmentation should be considered first-line surgical therapy for those with gastroesophageal reflux disease, based on the results of this study,” he said.

The 2-year results of the prospective, multicenter study were the basis of the FDA approval of the device, described by the manufacturer, Torax Medical, as a “small implant [composed] of interlinked titanium beads with magnetic cores,” implanted during standard laparoscopy. The magnetic attraction between the beads augments the existing esophageal sphincter’s barrier function to prevent reflux,” according to the company.

The study enrolled 100 patients with reflux disease with a median age of 53 years, who had experienced typical heartburn for at least 6 months with or without regurgitation and were taking PPIs daily for at least 3 months (median use 5 years). Patients had GERD for a median of 10 years (range: 1-40 years). People who had any type of previous gastric or esophageal surgery, Barrett’s esophagus, a hiatal hernia greater than 3 cm, a body mass index over 35 kg/m², or grade C or D esophagitis were excluded.

The device was implanted in all patients, who served as their own controls; 85 patients were followed through 5 years (6 were lost to follow-up, the device was explanted in 6 patients, 2 patients did not consent to extended follow-up, and 1 patient died of an unrelated cancer). The median procedure time was 36 minutes with a range of 7-125 minutes); all procedures were successfully completed with no intraoperative complications and all patients were discharged within 24 hours on an unrestricted diet.

The median total Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score at baseline was 27 points among those not on PPIs and 11 points on PPIs, dropping to 4 points at 5 years off PPIs. At baseline, 95% of patients expressed dissatisfaction related to reflux, which dropped to 7% at year 5. Moderate to severe heartburn was reported by 89% at baseline, dropping to about 12% at year 5. The proportion of patients experiencing moderate to severe regurgitation dropped from 57% at baseline to about 1% at 5 years, Dr. Ganz said.

At baseline, 100% were taking PPIs every day, compared with 15% at 5 years. (At 5 years, 75% had discontinued PPIs, and about 9% reported PRN use only). Grade A and B esophagitis decreased from 40% at baseline to 16% at 5 years, at which point most cases were grade A, and there were no patients with grade C or D esophagitis, he said. In addition, at 5 years, 100% of patients “reported the ability to belch, and those needing to vomit – about 16% – reported the ability to vomit,” demonstrating that normal physiology was preserved with the device.

At 5 years, there were no device erosions or migrations, or any significant adverse events other than dysphagia, which “was typically mild and not associated with weight loss and tended to resolve over time,” from about 70% in the first few weeks after surgery to 11% at 1 year and 7% at 5 years, Dr. Ganz said.

In seven cases, the device was removed laparoscopically, with no complications and gastric anatomy was preserved for future treatments. All removals were elective. The device was removed in four patients because of dysphagia, which completely resolved in those patients. One patient had the device removed because of vomiting of unknown cause that persisted after removal. Another two patients who “had the device removed for disease management” continued to experience reflux and had “uneventful” Nissen fundoplication,” he said.

“Five years after magnetic augmentation, we have demonstrated objective evidence of reduction in acid exposure and in the majority of patients, normalized pH [and] we demonstrated significant and durable improvement in all group parameters measured, with preservation of fundic anatomy and normal physiology, with the ability to belch and vomit,” Dr. Ganz concluded. The results also show that the “procedure is reproducible, safe and reversible if necessary,” he added, noting that one of the limitations of the study was that subjects served as their own controls. During the discussion period, he was asked about hiatal hernia repairs, an apparent trend to “decay” from years 1 to 5 in some parameters measured, and dysphagia after the procedure.

About 40% of the patients in the study had a hiatal hernia, and about one-third of these patients had a hernia repair. A subgroup analysis of the data is being performed to evaluate the impact of hernia repair, Dr. Ganz said.

PPI use increased from 8% in year 4, to 15% in year 5. The reason for this s difficult to determine but “even though there is a bit of a decay, patients are still quite satisfied at 5 years,” Dr. Ganz remarked, also referring to the marked impact on regurgitation. Many U.S. patients use PPIs for reasons other than reflux, and studies show that many patients are on PPIs after the Nissen procedure in the absence of pathologic pH scores, he pointed out.

Compared with the type of dysphagia patients experience after the Nissen procedure, which is immediate and improves with time, Dr. Ganz said that the dysphagia associated with the device “seemed to peak around 2 weeks and then it slowly improved with time, so this may be more of a scar tissue–associated dysphagia than an edema dysphagia, but … it does improve with time.

Three-year results of the study were published in 2013 (N. Engl. J. Med. 2013;368:719-72), Dr. Ganz was the lead author.

The study was funded by Torax Medical. Dr. Ganz had no disclosures related to the topic of this presentation.

*This story was updated 7/9/2015.

[email protected]

WASHINGTON – Five-year follow-up data on the magnetic device approved for treating gastroesophageal reflux disease confirm its long-term safety and efficacy, Dr. Robert A. Ganz reported at the annual Digestive Disease Week.

Five years after device implantation, the proportion of patients experiencing moderate to severe regurgitation had dropped to about 1%, from almost 60% at baseline, and two-thirds of patients were not taking any proton pump inhibitors (PPIs), said Dr. Ganz, chief of gastroenterology at Abbott Northwestern Hospital, Minneapolis, and one of the study investigators. These were among the results of the study that evaluated the device, the LINX Reflux Management System. The device was approved by the Food and Drug Administration FDA) in 2012 and is for the treatment of people with GERD as defined by abnormal pH testing, who continue to have chronic GERD symptoms that persist despite maximum medical therapy for the treatment of reflux.

“Magnetic sphincter augmentation should be considered first-line surgical therapy for those with gastroesophageal reflux disease, based on the results of this study,” he said.

The 2-year results of the prospective, multicenter study were the basis of the FDA approval of the device, described by the manufacturer, Torax Medical, as a “small implant [composed] of interlinked titanium beads with magnetic cores,” implanted during standard laparoscopy. The magnetic attraction between the beads augments the existing esophageal sphincter’s barrier function to prevent reflux,” according to the company.

The study enrolled 100 patients with reflux disease with a median age of 53 years, who had experienced typical heartburn for at least 6 months with or without regurgitation and were taking PPIs daily for at least 3 months (median use 5 years). Patients had GERD for a median of 10 years (range: 1-40 years). People who had any type of previous gastric or esophageal surgery, Barrett’s esophagus, a hiatal hernia greater than 3 cm, a body mass index over 35 kg/m², or grade C or D esophagitis were excluded.

The device was implanted in all patients, who served as their own controls; 85 patients were followed through 5 years (6 were lost to follow-up, the device was explanted in 6 patients, 2 patients did not consent to extended follow-up, and 1 patient died of an unrelated cancer). The median procedure time was 36 minutes with a range of 7-125 minutes); all procedures were successfully completed with no intraoperative complications and all patients were discharged within 24 hours on an unrestricted diet.

The median total Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score at baseline was 27 points among those not on PPIs and 11 points on PPIs, dropping to 4 points at 5 years off PPIs. At baseline, 95% of patients expressed dissatisfaction related to reflux, which dropped to 7% at year 5. Moderate to severe heartburn was reported by 89% at baseline, dropping to about 12% at year 5. The proportion of patients experiencing moderate to severe regurgitation dropped from 57% at baseline to about 1% at 5 years, Dr. Ganz said.

At baseline, 100% were taking PPIs every day, compared with 15% at 5 years. (At 5 years, 75% had discontinued PPIs, and about 9% reported PRN use only). Grade A and B esophagitis decreased from 40% at baseline to 16% at 5 years, at which point most cases were grade A, and there were no patients with grade C or D esophagitis, he said. In addition, at 5 years, 100% of patients “reported the ability to belch, and those needing to vomit – about 16% – reported the ability to vomit,” demonstrating that normal physiology was preserved with the device.

At 5 years, there were no device erosions or migrations, or any significant adverse events other than dysphagia, which “was typically mild and not associated with weight loss and tended to resolve over time,” from about 70% in the first few weeks after surgery to 11% at 1 year and 7% at 5 years, Dr. Ganz said.

In seven cases, the device was removed laparoscopically, with no complications and gastric anatomy was preserved for future treatments. All removals were elective. The device was removed in four patients because of dysphagia, which completely resolved in those patients. One patient had the device removed because of vomiting of unknown cause that persisted after removal. Another two patients who “had the device removed for disease management” continued to experience reflux and had “uneventful” Nissen fundoplication,” he said.

“Five years after magnetic augmentation, we have demonstrated objective evidence of reduction in acid exposure and in the majority of patients, normalized pH [and] we demonstrated significant and durable improvement in all group parameters measured, with preservation of fundic anatomy and normal physiology, with the ability to belch and vomit,” Dr. Ganz concluded. The results also show that the “procedure is reproducible, safe and reversible if necessary,” he added, noting that one of the limitations of the study was that subjects served as their own controls. During the discussion period, he was asked about hiatal hernia repairs, an apparent trend to “decay” from years 1 to 5 in some parameters measured, and dysphagia after the procedure.

About 40% of the patients in the study had a hiatal hernia, and about one-third of these patients had a hernia repair. A subgroup analysis of the data is being performed to evaluate the impact of hernia repair, Dr. Ganz said.

PPI use increased from 8% in year 4, to 15% in year 5. The reason for this s difficult to determine but “even though there is a bit of a decay, patients are still quite satisfied at 5 years,” Dr. Ganz remarked, also referring to the marked impact on regurgitation. Many U.S. patients use PPIs for reasons other than reflux, and studies show that many patients are on PPIs after the Nissen procedure in the absence of pathologic pH scores, he pointed out.

Compared with the type of dysphagia patients experience after the Nissen procedure, which is immediate and improves with time, Dr. Ganz said that the dysphagia associated with the device “seemed to peak around 2 weeks and then it slowly improved with time, so this may be more of a scar tissue–associated dysphagia than an edema dysphagia, but … it does improve with time.

Three-year results of the study were published in 2013 (N. Engl. J. Med. 2013;368:719-72), Dr. Ganz was the lead author.

The study was funded by Torax Medical. Dr. Ganz had no disclosures related to the topic of this presentation.

*This story was updated 7/9/2015.

[email protected]

WASHINGTON – Five-year follow-up data on the magnetic device approved for treating gastroesophageal reflux disease confirm its long-term safety and efficacy, Dr. Robert A. Ganz reported at the annual Digestive Disease Week.

Five years after device implantation, the proportion of patients experiencing moderate to severe regurgitation had dropped to about 1%, from almost 60% at baseline, and two-thirds of patients were not taking any proton pump inhibitors (PPIs), said Dr. Ganz, chief of gastroenterology at Abbott Northwestern Hospital, Minneapolis, and one of the study investigators. These were among the results of the study that evaluated the device, the LINX Reflux Management System. The device was approved by the Food and Drug Administration FDA) in 2012 and is for the treatment of people with GERD as defined by abnormal pH testing, who continue to have chronic GERD symptoms that persist despite maximum medical therapy for the treatment of reflux.

“Magnetic sphincter augmentation should be considered first-line surgical therapy for those with gastroesophageal reflux disease, based on the results of this study,” he said.

The 2-year results of the prospective, multicenter study were the basis of the FDA approval of the device, described by the manufacturer, Torax Medical, as a “small implant [composed] of interlinked titanium beads with magnetic cores,” implanted during standard laparoscopy. The magnetic attraction between the beads augments the existing esophageal sphincter’s barrier function to prevent reflux,” according to the company.

The study enrolled 100 patients with reflux disease with a median age of 53 years, who had experienced typical heartburn for at least 6 months with or without regurgitation and were taking PPIs daily for at least 3 months (median use 5 years). Patients had GERD for a median of 10 years (range: 1-40 years). People who had any type of previous gastric or esophageal surgery, Barrett’s esophagus, a hiatal hernia greater than 3 cm, a body mass index over 35 kg/m², or grade C or D esophagitis were excluded.

The device was implanted in all patients, who served as their own controls; 85 patients were followed through 5 years (6 were lost to follow-up, the device was explanted in 6 patients, 2 patients did not consent to extended follow-up, and 1 patient died of an unrelated cancer). The median procedure time was 36 minutes with a range of 7-125 minutes); all procedures were successfully completed with no intraoperative complications and all patients were discharged within 24 hours on an unrestricted diet.

The median total Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score at baseline was 27 points among those not on PPIs and 11 points on PPIs, dropping to 4 points at 5 years off PPIs. At baseline, 95% of patients expressed dissatisfaction related to reflux, which dropped to 7% at year 5. Moderate to severe heartburn was reported by 89% at baseline, dropping to about 12% at year 5. The proportion of patients experiencing moderate to severe regurgitation dropped from 57% at baseline to about 1% at 5 years, Dr. Ganz said.

At baseline, 100% were taking PPIs every day, compared with 15% at 5 years. (At 5 years, 75% had discontinued PPIs, and about 9% reported PRN use only). Grade A and B esophagitis decreased from 40% at baseline to 16% at 5 years, at which point most cases were grade A, and there were no patients with grade C or D esophagitis, he said. In addition, at 5 years, 100% of patients “reported the ability to belch, and those needing to vomit – about 16% – reported the ability to vomit,” demonstrating that normal physiology was preserved with the device.

At 5 years, there were no device erosions or migrations, or any significant adverse events other than dysphagia, which “was typically mild and not associated with weight loss and tended to resolve over time,” from about 70% in the first few weeks after surgery to 11% at 1 year and 7% at 5 years, Dr. Ganz said.

In seven cases, the device was removed laparoscopically, with no complications and gastric anatomy was preserved for future treatments. All removals were elective. The device was removed in four patients because of dysphagia, which completely resolved in those patients. One patient had the device removed because of vomiting of unknown cause that persisted after removal. Another two patients who “had the device removed for disease management” continued to experience reflux and had “uneventful” Nissen fundoplication,” he said.

“Five years after magnetic augmentation, we have demonstrated objective evidence of reduction in acid exposure and in the majority of patients, normalized pH [and] we demonstrated significant and durable improvement in all group parameters measured, with preservation of fundic anatomy and normal physiology, with the ability to belch and vomit,” Dr. Ganz concluded. The results also show that the “procedure is reproducible, safe and reversible if necessary,” he added, noting that one of the limitations of the study was that subjects served as their own controls. During the discussion period, he was asked about hiatal hernia repairs, an apparent trend to “decay” from years 1 to 5 in some parameters measured, and dysphagia after the procedure.

About 40% of the patients in the study had a hiatal hernia, and about one-third of these patients had a hernia repair. A subgroup analysis of the data is being performed to evaluate the impact of hernia repair, Dr. Ganz said.

PPI use increased from 8% in year 4, to 15% in year 5. The reason for this s difficult to determine but “even though there is a bit of a decay, patients are still quite satisfied at 5 years,” Dr. Ganz remarked, also referring to the marked impact on regurgitation. Many U.S. patients use PPIs for reasons other than reflux, and studies show that many patients are on PPIs after the Nissen procedure in the absence of pathologic pH scores, he pointed out.

Compared with the type of dysphagia patients experience after the Nissen procedure, which is immediate and improves with time, Dr. Ganz said that the dysphagia associated with the device “seemed to peak around 2 weeks and then it slowly improved with time, so this may be more of a scar tissue–associated dysphagia than an edema dysphagia, but … it does improve with time.

Three-year results of the study were published in 2013 (N. Engl. J. Med. 2013;368:719-72), Dr. Ganz was the lead author.

The study was funded by Torax Medical. Dr. Ganz had no disclosures related to the topic of this presentation.

*This story was updated 7/9/2015.

[email protected]

A 38-year-old man presents to dermatology with what he assumes is poison ivy: an itchy, blistery rash that usually appears in the summer, more years than not. Each year, it’s a bit worse in terms of extent and symptomatology, despite his efforts to avoid the problem altogether.

The rash pretty consistently manifests on his leg, although there are other areas of involvement. Equally predictable, at this point, is his wife’s reaction: She banishes him to the couch for fear of “catching” whatever he has.

After so many years’ experience with the condition, the patient is understandably alert to coming in contact with the offending plant. He has even taken photos of it, to demonstrate how abundantly it grows in his yard.

EXAMINATION
The patient’s lesions are classic collections of vesicles crisscrossing his legs in linear configurations. There is faint underlying erythema. Smaller but similar lesions are scattered over his arms and trunk; the patient is sure he spread the rash with his scratching.

The plant in the patient’s photos has five dart-shaped leaves with uniformly serrated margins extending from a single stem. It grows as a vine on fences and masonry. He has scrupulously avoided contact with it and therefore cannot understand how he keeps developing the rash.

What is the diagnosis?

DISCUSSION
It has been said that humor is tragedy plus time; certain skin diseases, such as shingles or poison ivy, certainly provide fodder. In the midst of an attack, however, these conditions can produce not only miserable symptoms of itching, pain, and sleeplessness, but also considerable mental anguish regarding contagion.

Repeated polls of the general public reveal an almost universal belief that poison ivy is contagious and that scratching spreads it around the body. Research, and a thorough knowledge of the pathophysiology involved, have long since disproven both concepts. So while the inclination to distance oneself from an affected person is understandable, there is actually no need to do so. For the patient, facing six weeks or more of isolation is no laughing matter (at least, until long after the fact).

This particular case highlights one other pertinent issue with poison ivy: As the photos established, the patient had carefully avoided the wrong plant. The five dart-shaped serrated leaves suggest Virginia creeper—certainly not poison ivy. This may sound like a minor issue, but it is quite possible that while the patient was steering clear of a harmless plant, he was in fact coming in contact with the one he should have been concerned about.

True poison ivy, Toxicodendron radicans, can develop as a bush, a vine that stays low to the ground, a small tree, or even a climbing vine that can reach 30 feet or higher into mature trees, especially along waterways or in low, boggy land. The vines can attain a thickness of more than 3 in and have a surface covered by tiny “rootlets,” giving them a shaggy look.

Regardless of the plant’s form, its leaves are always found in threes, protruding from the same stem. The leaves are diamond shaped, can reach a length of 10 in, and often have a single notch on the margin that is said to resemble the outline of a thumb. The plant produces white berries in late summer or early fall.

It has been estimated that the number of poison ivy plants has doubled since 1960, for at least two reasons. First, an increase in population has led to more land being cleared for housing; many properties now border woodlands, which are an ideal environment for this plant.

Second, and more surprising, poison ivy thrives in a CO₂-rich environment. Carbon dioxide in the atmosphere has increased significantly in the past 50 years and will continue to do so. Experts predict that the density of poison ivy will double again in the next 20 years as a result. The potency of the urushiol, the offending substance in the stems and leaves, is expected to increase as well.

The patient (height, 6’3” and weight, > 300 lb) was treated with a 60-mg IM injection of triamcinolone, a two-week, 40-mg taper of prednisone, and twice-daily application of betamethasone cream. This, of course, followed a discussion of the risks versus benefits of such a course of action.

TAKE-HOME LEARNING POINTS
• Climbing vines with five serrated leaves coming off the same stem are probably Virginia creeper and not poison ivy.

• Poison ivy is not contagious, cannot be spread by scratching, and is not poisonous in any way.

• The rash produced by poison ivy exposure can be severe and can last six weeks or more without treatment.

• The number of poison ivy plants has doubled in the past 50 years and is expected to double again within 20 years. The potency of the plant’s allergen is also expected to increase. 

A 38-year-old man presents to dermatology with what he assumes is poison ivy: an itchy, blistery rash that usually appears in the summer, more years than not. Each year, it’s a bit worse in terms of extent and symptomatology, despite his efforts to avoid the problem altogether.

The rash pretty consistently manifests on his leg, although there are other areas of involvement. Equally predictable, at this point, is his wife’s reaction: She banishes him to the couch for fear of “catching” whatever he has.

After so many years’ experience with the condition, the patient is understandably alert to coming in contact with the offending plant. He has even taken photos of it, to demonstrate how abundantly it grows in his yard.

EXAMINATION
The patient’s lesions are classic collections of vesicles crisscrossing his legs in linear configurations. There is faint underlying erythema. Smaller but similar lesions are scattered over his arms and trunk; the patient is sure he spread the rash with his scratching.

The plant in the patient’s photos has five dart-shaped leaves with uniformly serrated margins extending from a single stem. It grows as a vine on fences and masonry. He has scrupulously avoided contact with it and therefore cannot understand how he keeps developing the rash.

What is the diagnosis?

DISCUSSION
It has been said that humor is tragedy plus time; certain skin diseases, such as shingles or poison ivy, certainly provide fodder. In the midst of an attack, however, these conditions can produce not only miserable symptoms of itching, pain, and sleeplessness, but also considerable mental anguish regarding contagion.

Repeated polls of the general public reveal an almost universal belief that poison ivy is contagious and that scratching spreads it around the body. Research, and a thorough knowledge of the pathophysiology involved, have long since disproven both concepts. So while the inclination to distance oneself from an affected person is understandable, there is actually no need to do so. For the patient, facing six weeks or more of isolation is no laughing matter (at least, until long after the fact).

This particular case highlights one other pertinent issue with poison ivy: As the photos established, the patient had carefully avoided the wrong plant. The five dart-shaped serrated leaves suggest Virginia creeper—certainly not poison ivy. This may sound like a minor issue, but it is quite possible that while the patient was steering clear of a harmless plant, he was in fact coming in contact with the one he should have been concerned about.

True poison ivy, Toxicodendron radicans, can develop as a bush, a vine that stays low to the ground, a small tree, or even a climbing vine that can reach 30 feet or higher into mature trees, especially along waterways or in low, boggy land. The vines can attain a thickness of more than 3 in and have a surface covered by tiny “rootlets,” giving them a shaggy look.

Regardless of the plant’s form, its leaves are always found in threes, protruding from the same stem. The leaves are diamond shaped, can reach a length of 10 in, and often have a single notch on the margin that is said to resemble the outline of a thumb. The plant produces white berries in late summer or early fall.

It has been estimated that the number of poison ivy plants has doubled since 1960, for at least two reasons. First, an increase in population has led to more land being cleared for housing; many properties now border woodlands, which are an ideal environment for this plant.

Second, and more surprising, poison ivy thrives in a CO₂-rich environment. Carbon dioxide in the atmosphere has increased significantly in the past 50 years and will continue to do so. Experts predict that the density of poison ivy will double again in the next 20 years as a result. The potency of the urushiol, the offending substance in the stems and leaves, is expected to increase as well.

The patient (height, 6’3” and weight, > 300 lb) was treated with a 60-mg IM injection of triamcinolone, a two-week, 40-mg taper of prednisone, and twice-daily application of betamethasone cream. This, of course, followed a discussion of the risks versus benefits of such a course of action.

TAKE-HOME LEARNING POINTS
• Climbing vines with five serrated leaves coming off the same stem are probably Virginia creeper and not poison ivy.

• Poison ivy is not contagious, cannot be spread by scratching, and is not poisonous in any way.

• The rash produced by poison ivy exposure can be severe and can last six weeks or more without treatment.

• The number of poison ivy plants has doubled in the past 50 years and is expected to double again within 20 years. The potency of the plant’s allergen is also expected to increase. 

A 38-year-old man presents to dermatology with what he assumes is poison ivy: an itchy, blistery rash that usually appears in the summer, more years than not. Each year, it’s a bit worse in terms of extent and symptomatology, despite his efforts to avoid the problem altogether.

The rash pretty consistently manifests on his leg, although there are other areas of involvement. Equally predictable, at this point, is his wife’s reaction: She banishes him to the couch for fear of “catching” whatever he has.

After so many years’ experience with the condition, the patient is understandably alert to coming in contact with the offending plant. He has even taken photos of it, to demonstrate how abundantly it grows in his yard.

EXAMINATION
The patient’s lesions are classic collections of vesicles crisscrossing his legs in linear configurations. There is faint underlying erythema. Smaller but similar lesions are scattered over his arms and trunk; the patient is sure he spread the rash with his scratching.

The plant in the patient’s photos has five dart-shaped leaves with uniformly serrated margins extending from a single stem. It grows as a vine on fences and masonry. He has scrupulously avoided contact with it and therefore cannot understand how he keeps developing the rash.

What is the diagnosis?

DISCUSSION
It has been said that humor is tragedy plus time; certain skin diseases, such as shingles or poison ivy, certainly provide fodder. In the midst of an attack, however, these conditions can produce not only miserable symptoms of itching, pain, and sleeplessness, but also considerable mental anguish regarding contagion.

Repeated polls of the general public reveal an almost universal belief that poison ivy is contagious and that scratching spreads it around the body. Research, and a thorough knowledge of the pathophysiology involved, have long since disproven both concepts. So while the inclination to distance oneself from an affected person is understandable, there is actually no need to do so. For the patient, facing six weeks or more of isolation is no laughing matter (at least, until long after the fact).

This particular case highlights one other pertinent issue with poison ivy: As the photos established, the patient had carefully avoided the wrong plant. The five dart-shaped serrated leaves suggest Virginia creeper—certainly not poison ivy. This may sound like a minor issue, but it is quite possible that while the patient was steering clear of a harmless plant, he was in fact coming in contact with the one he should have been concerned about.

True poison ivy, Toxicodendron radicans, can develop as a bush, a vine that stays low to the ground, a small tree, or even a climbing vine that can reach 30 feet or higher into mature trees, especially along waterways or in low, boggy land. The vines can attain a thickness of more than 3 in and have a surface covered by tiny “rootlets,” giving them a shaggy look.

Regardless of the plant’s form, its leaves are always found in threes, protruding from the same stem. The leaves are diamond shaped, can reach a length of 10 in, and often have a single notch on the margin that is said to resemble the outline of a thumb. The plant produces white berries in late summer or early fall.

It has been estimated that the number of poison ivy plants has doubled since 1960, for at least two reasons. First, an increase in population has led to more land being cleared for housing; many properties now border woodlands, which are an ideal environment for this plant.

Second, and more surprising, poison ivy thrives in a CO₂-rich environment. Carbon dioxide in the atmosphere has increased significantly in the past 50 years and will continue to do so. Experts predict that the density of poison ivy will double again in the next 20 years as a result. The potency of the urushiol, the offending substance in the stems and leaves, is expected to increase as well.

The patient (height, 6’3” and weight, > 300 lb) was treated with a 60-mg IM injection of triamcinolone, a two-week, 40-mg taper of prednisone, and twice-daily application of betamethasone cream. This, of course, followed a discussion of the risks versus benefits of such a course of action.

TAKE-HOME LEARNING POINTS
• Climbing vines with five serrated leaves coming off the same stem are probably Virginia creeper and not poison ivy.

• Poison ivy is not contagious, cannot be spread by scratching, and is not poisonous in any way.

• The rash produced by poison ivy exposure can be severe and can last six weeks or more without treatment.

• The number of poison ivy plants has doubled in the past 50 years and is expected to double again within 20 years. The potency of the plant’s allergen is also expected to increase. 

Excerpt of our interviews with Choosing Wisely, hospitalist Manya Gupta, MD, an assistant professor in the department of internal medicine of Rush University Medical Center in Chicago, discusses an example of a Choosing Wisely program.

Excerpt of our interviews with Choosing Wisely, hospitalist Manya Gupta, MD, an assistant professor in the department of internal medicine of Rush University Medical Center in Chicago, discusses an example of a Choosing Wisely program.

Excerpt of our interviews with Choosing Wisely, hospitalist Manya Gupta, MD, an assistant professor in the department of internal medicine of Rush University Medical Center in Chicago, discusses an example of a Choosing Wisely program.

Cheryl DeVita, senior search consultant at Cejka Search, Inc., in St. Louis, Mo., offers advice on evaluating contracts and hospitalist groups.

Cheryl DeVita, senior search consultant at Cejka Search, Inc., in St. Louis, Mo., offers advice on evaluating contracts and hospitalist groups.

Cheryl DeVita, senior search consultant at Cejka Search, Inc., in St. Louis, Mo., offers advice on evaluating contracts and hospitalist groups.

ROBERT COBEN, MD, Program director of the gastroenterology fellowship program at Thomas Jefferson University Hospital in Philadelphia, discusses GI bleeds and colon cancer.

ROBERT COBEN, MD, Program director of the gastroenterology fellowship program at Thomas Jefferson University Hospital in Philadelphia, discusses GI bleeds and colon cancer.

ROBERT COBEN, MD, Program director of the gastroenterology fellowship program at Thomas Jefferson University Hospital in Philadelphia, discusses GI bleeds and colon cancer.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

VANCOUVER, B.C. – Naloxone lotion appears to be a safe and effective treatment for the severe chronic itching that occurs in most patients with cutaneous T-cell lymphoma, Dr. Madeleine Duvic reported at the World Congress of Dermatology.

A major unmet need exists for better treatments for pruritis in CTCL. Antihistamines are generally ineffective. Chemotherapeutic agents provide little relief. Moreover, it has been estimated that up to half of all patients with CTCL die as a result of systemic infections arising secondary to pruritic skin excoriations, according to Dr. Duvic, professor of medicine and dermatology at the University of Texas and MD Anderson Cancer Center, Houston.

Naloxone is a pure opiate antagonist with no agonist effects. Naloxone lotion is an investigational agent that has received orphan drug status for treatment of pruritis in CTCL and a fast-track evaluation designation from the Food and Drug Administration.

Dr. Duvic presented a double-blind, vehicle-controlled, multicenter, crossover study involving 15 CTCL patients with severe itching. They were assigned to apply naloxone lotion 0.5% or its vehicle four times daily for 8 days and then cross over to the other regimen for another 8 days following a washout period.

After 8 days of naloxone lotion, patients reported a mean 66% reduction in itch severity from baseline on a visual analog scale, a significantly better result than the 45% reduction on vehicle.

The study suffered from small numbers, as four patients withdrew during part 1 while on vehicle, two dropped out while on naloxone lotion, and one was excluded for a concomitant medication violation. Of the nine patients available for Physician Global Assessment, seven were rated better or much better. Seven of the nine patients also rated themselves as globally better or much better while on naloxone lotion. These ratings were numerically better than while patients were on vehicle.

Adverse events were limited to two cases of mild or moderate application-site erythema.

The study was funded by Elorac. Dr. Duvic reported having no financial conflicts. She noted that the University of Texas received a research grant to conduct the study.

[email protected]

VANCOUVER, B.C. – Naloxone lotion appears to be a safe and effective treatment for the severe chronic itching that occurs in most patients with cutaneous T-cell lymphoma, Dr. Madeleine Duvic reported at the World Congress of Dermatology.

A major unmet need exists for better treatments for pruritis in CTCL. Antihistamines are generally ineffective. Chemotherapeutic agents provide little relief. Moreover, it has been estimated that up to half of all patients with CTCL die as a result of systemic infections arising secondary to pruritic skin excoriations, according to Dr. Duvic, professor of medicine and dermatology at the University of Texas and MD Anderson Cancer Center, Houston.

Naloxone is a pure opiate antagonist with no agonist effects. Naloxone lotion is an investigational agent that has received orphan drug status for treatment of pruritis in CTCL and a fast-track evaluation designation from the Food and Drug Administration.

Dr. Duvic presented a double-blind, vehicle-controlled, multicenter, crossover study involving 15 CTCL patients with severe itching. They were assigned to apply naloxone lotion 0.5% or its vehicle four times daily for 8 days and then cross over to the other regimen for another 8 days following a washout period.

After 8 days of naloxone lotion, patients reported a mean 66% reduction in itch severity from baseline on a visual analog scale, a significantly better result than the 45% reduction on vehicle.

The study suffered from small numbers, as four patients withdrew during part 1 while on vehicle, two dropped out while on naloxone lotion, and one was excluded for a concomitant medication violation. Of the nine patients available for Physician Global Assessment, seven were rated better or much better. Seven of the nine patients also rated themselves as globally better or much better while on naloxone lotion. These ratings were numerically better than while patients were on vehicle.

Adverse events were limited to two cases of mild or moderate application-site erythema.

The study was funded by Elorac. Dr. Duvic reported having no financial conflicts. She noted that the University of Texas received a research grant to conduct the study.

[email protected]

VANCOUVER, B.C. – Naloxone lotion appears to be a safe and effective treatment for the severe chronic itching that occurs in most patients with cutaneous T-cell lymphoma, Dr. Madeleine Duvic reported at the World Congress of Dermatology.

A major unmet need exists for better treatments for pruritis in CTCL. Antihistamines are generally ineffective. Chemotherapeutic agents provide little relief. Moreover, it has been estimated that up to half of all patients with CTCL die as a result of systemic infections arising secondary to pruritic skin excoriations, according to Dr. Duvic, professor of medicine and dermatology at the University of Texas and MD Anderson Cancer Center, Houston.

Naloxone is a pure opiate antagonist with no agonist effects. Naloxone lotion is an investigational agent that has received orphan drug status for treatment of pruritis in CTCL and a fast-track evaluation designation from the Food and Drug Administration.

Dr. Duvic presented a double-blind, vehicle-controlled, multicenter, crossover study involving 15 CTCL patients with severe itching. They were assigned to apply naloxone lotion 0.5% or its vehicle four times daily for 8 days and then cross over to the other regimen for another 8 days following a washout period.

After 8 days of naloxone lotion, patients reported a mean 66% reduction in itch severity from baseline on a visual analog scale, a significantly better result than the 45% reduction on vehicle.

The study suffered from small numbers, as four patients withdrew during part 1 while on vehicle, two dropped out while on naloxone lotion, and one was excluded for a concomitant medication violation. Of the nine patients available for Physician Global Assessment, seven were rated better or much better. Seven of the nine patients also rated themselves as globally better or much better while on naloxone lotion. These ratings were numerically better than while patients were on vehicle.

Adverse events were limited to two cases of mild or moderate application-site erythema.

The study was funded by Elorac. Dr. Duvic reported having no financial conflicts. She noted that the University of Texas received a research grant to conduct the study.

[email protected]

Patient choice, contraceptive effectiveness, and medical eligibility all need to be incorporated into the contraceptive counseling for reproductive-age women who have cancer or are in remission. Based on these principles, women can minimize the risk of an unintended pregnancy, continue to receive necessary adjuvant or preventive therapy, and maintain high levels of contraception satisfaction.

The Centers for Disease Control and Prevention (CDC) has published medical eligibility criteria (MEC) to assist providers in selecting medically appropriate contraception for women with various health conditions, including cancer (MMWR Recomm. Rep. 2010;59(RR-4):1-6).

Certain classes of hormonal contraception are contraindicated in specific cancer types. It is important to note that the copper intrauterine device (ParaGard) is very effective (with a first-year failure rate of 0.8%) and has no cancer-related contraindications. Any contraceptive with estrogen or progesterone is relatively contraindicated in hormonally mediated cancers, including breast, endometrial, or other cancers that have estrogen (ER) or progesterone (PR) positive receptors. Combined hormonal contraception is contraindicated even in breast cancers that are ER/PR negative for the first 5 years, after which they are CDC MEC category 3 (risks likely outweigh the benefits).

Venous thromboembolism (VTE) is an important cancer-related morbidity. Active cancer increases the risk of VTE by fourfold, which is further increased if the patient is on chemotherapy (Arch. Intern. Med. 2000;160:809-15). Estrogen is known to increase thrombotic risk, and therefore it is contraindicated in any patient at risk for VTE or with a history of a VTE. There is some debate about the use of progestin-only contraceptives in those at risk of (or with a history of) VTE. The best evidence and CDC guidelines indicate that progestin-only methods can be used in patients with cancer or with a history of VTE. Importantly, no known association exists between emergency contraception and VTE (Obstet. Gynecol. 2010;115:1100-9).

Other cancer-specific problems that may impact contraception include thrombocytopenia, gastrointestinal side effects, and drug interactions. Thrombocytopenia may exacerbate or cause abnormal uterine bleeding. Therefore, menstrual suppression with continuous combined hormonal contraception or progestin-only methods, including the hormonal IUD and implant, may be ideal. Regarding gastrointestinal side effects, emesis and mucositis from cancer and treatment may reduce absorption of oral contraceptives, so alternatives should be considered. Antacids, analgesics, antifungals, anticonvulsants, and antiretrovirals are all known to affect hepatic metabolism and may affect oral contraceptive efficacy.

Given the possibility of chemotherapy-induced immunosuppression, there is a theoretical concern about the infectious risk of an indwelling foreign body such as an IUD or implant. The best evidence to date, however, does not support an increased risk, even in the setting of neutropenia. Chemotherapy also increases osteoporosis. Gynecologists should use caution with depot medroxyprogesterone acetate (DMPA), although there is no absolute contraindication, especially for shorter durations of use.

Many breast cancer patients are prescribed tamoxifen as adjuvant therapy, but the antiestrogenic effects of tamoxifen may not prevent pregnancy (Cancer Imaging 2008;8:135-45). Therefore, it is critical for reproductive-age women taking tamoxifen to be given effective contraception. Experts have not reached a consensus on the use of levonorgestrel intrauterine systems (LNG-IUS, Mirena, or Skyla) in the setting of breast cancer.

On the one hand, patients on long-term tamoxifen may benefit from the endometrial protective effect of an LNG-IUS (Lancet 2000;356:1711-7). It is uncertain if women with an LNG-IUS in place at the time of breast cancer diagnosis should have the device removed. Placing a LNG-IUS is contraindicated in all cases of active cancer, but if the patient has no evidence of disease for more than 5 years, the CDC lists the LNG-IUS as category 3. Expert consensus is that studies are needed with LNG-IUS use in women with breast cancer and that use of the LNG-IUS in this population should be made with careful consideration of the risks and benefits (Fertil. Steril. 2008;90:17-22; Contraception 2012;86:191-8).

Physicians should consider the contraceptive needs of women who are actively being or have recently been treated for cancer, as 17% of female cancers occur in women of reproductive age. The copper IUD is a highly effective option with very few contraindications. In patients with a history of non–hormonal related cancer (and without any history of VTE), all contraceptive options can be considered, including those containing estrogen. Estrogen-containing contraceptives should be avoided in those with a history of hormonally related cancers. Those not familiar with the wide array of options should consider referring early, and family planning specialists should consider medical eligibility while counseling women about the most effective contraceptive options.

Dr. Zerden is a family planning fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. He reported having no financial disclosures. E-mail Dr. Zerden at [email protected].

Patient choice, contraceptive effectiveness, and medical eligibility all need to be incorporated into the contraceptive counseling for reproductive-age women who have cancer or are in remission. Based on these principles, women can minimize the risk of an unintended pregnancy, continue to receive necessary adjuvant or preventive therapy, and maintain high levels of contraception satisfaction.

The Centers for Disease Control and Prevention (CDC) has published medical eligibility criteria (MEC) to assist providers in selecting medically appropriate contraception for women with various health conditions, including cancer (MMWR Recomm. Rep. 2010;59(RR-4):1-6).

Certain classes of hormonal contraception are contraindicated in specific cancer types. It is important to note that the copper intrauterine device (ParaGard) is very effective (with a first-year failure rate of 0.8%) and has no cancer-related contraindications. Any contraceptive with estrogen or progesterone is relatively contraindicated in hormonally mediated cancers, including breast, endometrial, or other cancers that have estrogen (ER) or progesterone (PR) positive receptors. Combined hormonal contraception is contraindicated even in breast cancers that are ER/PR negative for the first 5 years, after which they are CDC MEC category 3 (risks likely outweigh the benefits).

Venous thromboembolism (VTE) is an important cancer-related morbidity. Active cancer increases the risk of VTE by fourfold, which is further increased if the patient is on chemotherapy (Arch. Intern. Med. 2000;160:809-15). Estrogen is known to increase thrombotic risk, and therefore it is contraindicated in any patient at risk for VTE or with a history of a VTE. There is some debate about the use of progestin-only contraceptives in those at risk of (or with a history of) VTE. The best evidence and CDC guidelines indicate that progestin-only methods can be used in patients with cancer or with a history of VTE. Importantly, no known association exists between emergency contraception and VTE (Obstet. Gynecol. 2010;115:1100-9).

Other cancer-specific problems that may impact contraception include thrombocytopenia, gastrointestinal side effects, and drug interactions. Thrombocytopenia may exacerbate or cause abnormal uterine bleeding. Therefore, menstrual suppression with continuous combined hormonal contraception or progestin-only methods, including the hormonal IUD and implant, may be ideal. Regarding gastrointestinal side effects, emesis and mucositis from cancer and treatment may reduce absorption of oral contraceptives, so alternatives should be considered. Antacids, analgesics, antifungals, anticonvulsants, and antiretrovirals are all known to affect hepatic metabolism and may affect oral contraceptive efficacy.

Given the possibility of chemotherapy-induced immunosuppression, there is a theoretical concern about the infectious risk of an indwelling foreign body such as an IUD or implant. The best evidence to date, however, does not support an increased risk, even in the setting of neutropenia. Chemotherapy also increases osteoporosis. Gynecologists should use caution with depot medroxyprogesterone acetate (DMPA), although there is no absolute contraindication, especially for shorter durations of use.

Many breast cancer patients are prescribed tamoxifen as adjuvant therapy, but the antiestrogenic effects of tamoxifen may not prevent pregnancy (Cancer Imaging 2008;8:135-45). Therefore, it is critical for reproductive-age women taking tamoxifen to be given effective contraception. Experts have not reached a consensus on the use of levonorgestrel intrauterine systems (LNG-IUS, Mirena, or Skyla) in the setting of breast cancer.

On the one hand, patients on long-term tamoxifen may benefit from the endometrial protective effect of an LNG-IUS (Lancet 2000;356:1711-7). It is uncertain if women with an LNG-IUS in place at the time of breast cancer diagnosis should have the device removed. Placing a LNG-IUS is contraindicated in all cases of active cancer, but if the patient has no evidence of disease for more than 5 years, the CDC lists the LNG-IUS as category 3. Expert consensus is that studies are needed with LNG-IUS use in women with breast cancer and that use of the LNG-IUS in this population should be made with careful consideration of the risks and benefits (Fertil. Steril. 2008;90:17-22; Contraception 2012;86:191-8).

Physicians should consider the contraceptive needs of women who are actively being or have recently been treated for cancer, as 17% of female cancers occur in women of reproductive age. The copper IUD is a highly effective option with very few contraindications. In patients with a history of non–hormonal related cancer (and without any history of VTE), all contraceptive options can be considered, including those containing estrogen. Estrogen-containing contraceptives should be avoided in those with a history of hormonally related cancers. Those not familiar with the wide array of options should consider referring early, and family planning specialists should consider medical eligibility while counseling women about the most effective contraceptive options.

Dr. Zerden is a family planning fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. He reported having no financial disclosures. E-mail Dr. Zerden at [email protected].

Patient choice, contraceptive effectiveness, and medical eligibility all need to be incorporated into the contraceptive counseling for reproductive-age women who have cancer or are in remission. Based on these principles, women can minimize the risk of an unintended pregnancy, continue to receive necessary adjuvant or preventive therapy, and maintain high levels of contraception satisfaction.

The Centers for Disease Control and Prevention (CDC) has published medical eligibility criteria (MEC) to assist providers in selecting medically appropriate contraception for women with various health conditions, including cancer (MMWR Recomm. Rep. 2010;59(RR-4):1-6).

Certain classes of hormonal contraception are contraindicated in specific cancer types. It is important to note that the copper intrauterine device (ParaGard) is very effective (with a first-year failure rate of 0.8%) and has no cancer-related contraindications. Any contraceptive with estrogen or progesterone is relatively contraindicated in hormonally mediated cancers, including breast, endometrial, or other cancers that have estrogen (ER) or progesterone (PR) positive receptors. Combined hormonal contraception is contraindicated even in breast cancers that are ER/PR negative for the first 5 years, after which they are CDC MEC category 3 (risks likely outweigh the benefits).

Venous thromboembolism (VTE) is an important cancer-related morbidity. Active cancer increases the risk of VTE by fourfold, which is further increased if the patient is on chemotherapy (Arch. Intern. Med. 2000;160:809-15). Estrogen is known to increase thrombotic risk, and therefore it is contraindicated in any patient at risk for VTE or with a history of a VTE. There is some debate about the use of progestin-only contraceptives in those at risk of (or with a history of) VTE. The best evidence and CDC guidelines indicate that progestin-only methods can be used in patients with cancer or with a history of VTE. Importantly, no known association exists between emergency contraception and VTE (Obstet. Gynecol. 2010;115:1100-9).

Other cancer-specific problems that may impact contraception include thrombocytopenia, gastrointestinal side effects, and drug interactions. Thrombocytopenia may exacerbate or cause abnormal uterine bleeding. Therefore, menstrual suppression with continuous combined hormonal contraception or progestin-only methods, including the hormonal IUD and implant, may be ideal. Regarding gastrointestinal side effects, emesis and mucositis from cancer and treatment may reduce absorption of oral contraceptives, so alternatives should be considered. Antacids, analgesics, antifungals, anticonvulsants, and antiretrovirals are all known to affect hepatic metabolism and may affect oral contraceptive efficacy.

Given the possibility of chemotherapy-induced immunosuppression, there is a theoretical concern about the infectious risk of an indwelling foreign body such as an IUD or implant. The best evidence to date, however, does not support an increased risk, even in the setting of neutropenia. Chemotherapy also increases osteoporosis. Gynecologists should use caution with depot medroxyprogesterone acetate (DMPA), although there is no absolute contraindication, especially for shorter durations of use.

Many breast cancer patients are prescribed tamoxifen as adjuvant therapy, but the antiestrogenic effects of tamoxifen may not prevent pregnancy (Cancer Imaging 2008;8:135-45). Therefore, it is critical for reproductive-age women taking tamoxifen to be given effective contraception. Experts have not reached a consensus on the use of levonorgestrel intrauterine systems (LNG-IUS, Mirena, or Skyla) in the setting of breast cancer.

On the one hand, patients on long-term tamoxifen may benefit from the endometrial protective effect of an LNG-IUS (Lancet 2000;356:1711-7). It is uncertain if women with an LNG-IUS in place at the time of breast cancer diagnosis should have the device removed. Placing a LNG-IUS is contraindicated in all cases of active cancer, but if the patient has no evidence of disease for more than 5 years, the CDC lists the LNG-IUS as category 3. Expert consensus is that studies are needed with LNG-IUS use in women with breast cancer and that use of the LNG-IUS in this population should be made with careful consideration of the risks and benefits (Fertil. Steril. 2008;90:17-22; Contraception 2012;86:191-8).

Physicians should consider the contraceptive needs of women who are actively being or have recently been treated for cancer, as 17% of female cancers occur in women of reproductive age. The copper IUD is a highly effective option with very few contraindications. In patients with a history of non–hormonal related cancer (and without any history of VTE), all contraceptive options can be considered, including those containing estrogen. Estrogen-containing contraceptives should be avoided in those with a history of hormonally related cancers. Those not familiar with the wide array of options should consider referring early, and family planning specialists should consider medical eligibility while counseling women about the most effective contraceptive options.

Dr. Zerden is a family planning fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. He reported having no financial disclosures. E-mail Dr. Zerden at [email protected].

(Reuters Health) - Not all U.S. stroke patients eligible for thrombolytic therapy actually receive it - and the odds of getting this therapy may depend on where they live, a large study finds.

Dr. James Burke of the University of Michigan and the VA Ann Arbor Health System and colleagues examined 844,241 hospital admissions for ischemic stroke from 2007 to 2010 among U.S. patients insured by Medicare.

They sorted patients into 3,436 different hospital service areas based on home postal code to assess regional variation in thrombolysis treatment rates.

Patients were 78 years old on average. About 57% were women, and most were white. The majority had hypertension and many also had diabetes, high cholesterol or arrhythmia.

Overall, just 3.9% of these patients received thrombolysis, the researchers report online June 2 in the journal Stroke. The treatment wasn't given at all in 20% of regions, and it was more likely to occur in places with higher population density.

In the 20 regions with the highest rates of thrombolysis, roughly 10% to 14% of patients received the treatment.

After accounting for the number of strokes in each region, the proportion of patients receiving thrombolysis ranged from 2.2% in the bottom fifth of regions to 5.9% in the top fifth.

Older patients, women and minorities were less likely to receive the treatment. Regions with the lowest proportion of college graduates also had a smaller percentage of people treated with thrombolysis.

Not every patient with stroke should receive thrombolysis. One study in Cincinnati estimated that about 6% of stroke patients would be eligible, but the new findings of higher rates in the highest-performing regions suggest that more patients could benefit if they could be transported more quickly to hospitals where thrombolysis is available, the authors say.

By boosting use of the treatment in regions where it's least likely to happen up to the level in places where the therapy is most common, researchers estimated that an additional 92,847 stroke patients might get thrombolysis, averting disability for 8,078 of them.

"Prompt recognition and reaction to warning signs and effective emergency service systems can minimize delays in pre-hospital dispatch, assessment and transport, and ultimately increase the number of stroke patients reaching the hospital and being prepared for thrombolytic therapy within the 4.5-hour time window," Dr. Maurizio Paciaroni, a stroke specialist at the University of Perugia in Italy who wasn't involved in the study, said by email.

"For a variety of reasons, only a minority of patients get to the hospital within the first couple hours of a stroke," Burke said by email. Patients might not recognize symptoms or call 911 soon enough, and even when they do seek help quickly they might not end up at a hospital that's equipped to provide thrombolysis, he added.

The best outcomes are for patients who receive thrombolysis within the first hour after the blood vessel becomes blocked, said Dr. Brian Silver, director of the Comprehensive Stroke Center at Rhode Island Hospital and researcher at Brown University.

"When patients don't receive this treatment, they are up to 50% less likely to have a better outcome," Silver, who wasn't involved with the study, said by email. "This means, for some, residual speech difficulties, paralysis, vision loss, cognitive impairment and depression."

Globally, 15 million people suffer strokes each year; five million of them die and another five million are left permanently disabled, according to the World Health Organization.

(Reuters Health) - Not all U.S. stroke patients eligible for thrombolytic therapy actually receive it - and the odds of getting this therapy may depend on where they live, a large study finds.

Dr. James Burke of the University of Michigan and the VA Ann Arbor Health System and colleagues examined 844,241 hospital admissions for ischemic stroke from 2007 to 2010 among U.S. patients insured by Medicare.

They sorted patients into 3,436 different hospital service areas based on home postal code to assess regional variation in thrombolysis treatment rates.

Patients were 78 years old on average. About 57% were women, and most were white. The majority had hypertension and many also had diabetes, high cholesterol or arrhythmia.

Overall, just 3.9% of these patients received thrombolysis, the researchers report online June 2 in the journal Stroke. The treatment wasn't given at all in 20% of regions, and it was more likely to occur in places with higher population density.

In the 20 regions with the highest rates of thrombolysis, roughly 10% to 14% of patients received the treatment.

After accounting for the number of strokes in each region, the proportion of patients receiving thrombolysis ranged from 2.2% in the bottom fifth of regions to 5.9% in the top fifth.

Older patients, women and minorities were less likely to receive the treatment. Regions with the lowest proportion of college graduates also had a smaller percentage of people treated with thrombolysis.

Not every patient with stroke should receive thrombolysis. One study in Cincinnati estimated that about 6% of stroke patients would be eligible, but the new findings of higher rates in the highest-performing regions suggest that more patients could benefit if they could be transported more quickly to hospitals where thrombolysis is available, the authors say.

By boosting use of the treatment in regions where it's least likely to happen up to the level in places where the therapy is most common, researchers estimated that an additional 92,847 stroke patients might get thrombolysis, averting disability for 8,078 of them.

"Prompt recognition and reaction to warning signs and effective emergency service systems can minimize delays in pre-hospital dispatch, assessment and transport, and ultimately increase the number of stroke patients reaching the hospital and being prepared for thrombolytic therapy within the 4.5-hour time window," Dr. Maurizio Paciaroni, a stroke specialist at the University of Perugia in Italy who wasn't involved in the study, said by email.

"For a variety of reasons, only a minority of patients get to the hospital within the first couple hours of a stroke," Burke said by email. Patients might not recognize symptoms or call 911 soon enough, and even when they do seek help quickly they might not end up at a hospital that's equipped to provide thrombolysis, he added.

The best outcomes are for patients who receive thrombolysis within the first hour after the blood vessel becomes blocked, said Dr. Brian Silver, director of the Comprehensive Stroke Center at Rhode Island Hospital and researcher at Brown University.

"When patients don't receive this treatment, they are up to 50% less likely to have a better outcome," Silver, who wasn't involved with the study, said by email. "This means, for some, residual speech difficulties, paralysis, vision loss, cognitive impairment and depression."

Globally, 15 million people suffer strokes each year; five million of them die and another five million are left permanently disabled, according to the World Health Organization.

(Reuters Health) - Not all U.S. stroke patients eligible for thrombolytic therapy actually receive it - and the odds of getting this therapy may depend on where they live, a large study finds.

Dr. James Burke of the University of Michigan and the VA Ann Arbor Health System and colleagues examined 844,241 hospital admissions for ischemic stroke from 2007 to 2010 among U.S. patients insured by Medicare.

They sorted patients into 3,436 different hospital service areas based on home postal code to assess regional variation in thrombolysis treatment rates.

Patients were 78 years old on average. About 57% were women, and most were white. The majority had hypertension and many also had diabetes, high cholesterol or arrhythmia.

Overall, just 3.9% of these patients received thrombolysis, the researchers report online June 2 in the journal Stroke. The treatment wasn't given at all in 20% of regions, and it was more likely to occur in places with higher population density.

In the 20 regions with the highest rates of thrombolysis, roughly 10% to 14% of patients received the treatment.

After accounting for the number of strokes in each region, the proportion of patients receiving thrombolysis ranged from 2.2% in the bottom fifth of regions to 5.9% in the top fifth.

Older patients, women and minorities were less likely to receive the treatment. Regions with the lowest proportion of college graduates also had a smaller percentage of people treated with thrombolysis.

Not every patient with stroke should receive thrombolysis. One study in Cincinnati estimated that about 6% of stroke patients would be eligible, but the new findings of higher rates in the highest-performing regions suggest that more patients could benefit if they could be transported more quickly to hospitals where thrombolysis is available, the authors say.

By boosting use of the treatment in regions where it's least likely to happen up to the level in places where the therapy is most common, researchers estimated that an additional 92,847 stroke patients might get thrombolysis, averting disability for 8,078 of them.

"Prompt recognition and reaction to warning signs and effective emergency service systems can minimize delays in pre-hospital dispatch, assessment and transport, and ultimately increase the number of stroke patients reaching the hospital and being prepared for thrombolytic therapy within the 4.5-hour time window," Dr. Maurizio Paciaroni, a stroke specialist at the University of Perugia in Italy who wasn't involved in the study, said by email.

"For a variety of reasons, only a minority of patients get to the hospital within the first couple hours of a stroke," Burke said by email. Patients might not recognize symptoms or call 911 soon enough, and even when they do seek help quickly they might not end up at a hospital that's equipped to provide thrombolysis, he added.

The best outcomes are for patients who receive thrombolysis within the first hour after the blood vessel becomes blocked, said Dr. Brian Silver, director of the Comprehensive Stroke Center at Rhode Island Hospital and researcher at Brown University.

"When patients don't receive this treatment, they are up to 50% less likely to have a better outcome," Silver, who wasn't involved with the study, said by email. "This means, for some, residual speech difficulties, paralysis, vision loss, cognitive impairment and depression."

Globally, 15 million people suffer strokes each year; five million of them die and another five million are left permanently disabled, according to the World Health Organization.

HSCT preparation

Photo by Chad McNeeley

VIENNA—Outcomes of hematopoietic stem cell transplant (HSCT) are encouraging in myelofibrosis (MF) patients who respond well to JAK inhibitors, according to researchers.

The group found that patients with the best response to JAK inhibition had a 2-year survival probability of 91% after HSCT, compared to 32% for patients with

leukemic transformation while on a JAK inhibitor.

In addition, receiving a JAK inhibitor until HSCT could prevent the return of MF-related symptoms.

Mohamed Shanavas, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, presented these findings at the 20th Congress of the European Hematology Association (abstract S450*).

The decision to undergo HSCT is a complex one in MF, particularly for those patients who are responding to JAK inhibitors. So Dr Shanavas and his colleagues undertook a retrospective, multicenter analysis to determine if there is an association between response to JAK inhibition and HSCT outcome.

The investigators analyzed the outcomes of 100 patients who had a first HSCT for primary MF, post-essential thrombocythemia MF, or post-polycythemia vera MF. Patients had to have exposure to a JAK inhibitor but no history of leukemic transformation prior to taking a JAK inhibitor.

Response criteria

The researchers stratified patients’ JAK1/2 response according to the following criteria:

• Group A: Clinical improvement: Fifty percent or greater reduction in palpable spleen length for spleen palpable by ≥ 10 cm, or complete resolution of splenomegaly for spleen < 10 cm
• Group B: Stable disease: Spleen response not meeting the criteria of clinical improvement
• Group C: A 10% to 19% increase in blasts, new onset of anemia requiring transfusions, or intolerance to treatment due to side effects
• Group D: Progressive disease: New splenomegaly > 5 cm, 100% increase in spleen 5-10 cm, or 50% increase in spleen > 10 cm
• Group E: Leukemic transformation: Bone marrow or circulating blasts ≥ 20%.

Patient and treatment characteristics

Patients were a median age of 59 (range, 32–72). Fifty-seven had primary MF, 21 had post-essential thrombocythemia MF, and 22 had post-polycythemia vera MF. Sixty-two patients had JAK2^V617F-mutated disease, 37 were wild-type, and 1 had unknown JAK status.

The majority of patients had intermediate-2 or high-risk disease according to their DIPSS scores, and 42 had a transplant comorbidity index score of 3 or greater.

Most patients (n=91) had ruxolitinib as their JAK inhibitor, 6 had momelotinib, and 3 had another inhibitor.

The median duration of JAK inhibitor therapy was 5 months (range, 1–36), and 66 patients were on treatment at the time of transplant. Thirty patients had previously discontinued JAK therapy, and the status of 4 was unknown.

In terms of their response to JAK inhibitors, 23 patients were in group A (clinical improvement), 31 in group B (stable disease), 15 in group C (increased blasts/transfusion need/intolerance), 18 in group D (progressive disease), and 13 in group E (leukemic transformation).

Fifty patients received a matched unrelated donor transplant, 36 had a matched sibling donor, and 14 had either a mismatched unrelated donor or a haploidentical transplant.

Fifty-six patients had a reduced-intensity conditioning regimen, and 44 had full intensity. Fifty percent of patients had T-cell depletion prior to transplant.

Outcomes

Patients who stopped JAK inhibitor therapy 6 or more days prior to transplant (n=20) experienced more “withdrawal symptoms”—the return of MF-related symptoms—than patients in whom the interval was less than 6 days (n=46). For the most part, withdrawal symptoms were non-severe in nature.

Two patients had fatal HSCT-related toxicity of venoocclusive disease, 4 had primary graft failure, and 4 had secondary graft failure. Forty-three percent of cytomegalovirus-seropositive patients had reactivation, 6 patients had Epstein-Barr virus reactivation, 6 had adenovirus or human polyomavirus BK infections, and 7 had invasive fungal infections.

Grade 2-4 acute graft-vs-host disease (GVHD) occurred in 37% of patients at day 100, and grade 3-4 occurred in 16%. Chronic GVHD of all grades occurred in 48% of patients, and extensive chronic GVHD occurred in 23%.

The cumulative incidence of relapse at 2 years was 17%, and non-relapse mortality was 28%. Overall survival (OS) was 61%.

“We analyzed this outcome based upon the response to JAK inhibitors,” Dr Shanavas said. “Patients who were deriving clinical improvement, group A, had a superior outcome, with a probability of survival of 91% at 2 years. Patients who had leukemic transformation, group E, had an inferior OS of 32% at 2 years.”

He noted that the outcomes appeared similar in the other 3 groups, so the researchers combined them for further analysis.

“As expected,” he said, “patients who had leukemic transformation had a significantly higher relapse rate than the other groups.”

The researchers then performed a multivariate analysis and found that response to JAK inhibitors, DIPSS score prior to JAK therapy, and donor type had a significant effect on OS.

The team concluded that prior exposure to JAK inhibitors does not have a negative effect on early HSCT outcomes. And actually, patients who undergo HSCT while responding to JAK inhibitors have encouraging outcomes.

*Information in the abstract differs from that presented at the meeting.

HSCT preparation

Photo by Chad McNeeley

VIENNA—Outcomes of hematopoietic stem cell transplant (HSCT) are encouraging in myelofibrosis (MF) patients who respond well to JAK inhibitors, according to researchers.

The group found that patients with the best response to JAK inhibition had a 2-year survival probability of 91% after HSCT, compared to 32% for patients with

leukemic transformation while on a JAK inhibitor.

In addition, receiving a JAK inhibitor until HSCT could prevent the return of MF-related symptoms.

Mohamed Shanavas, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, presented these findings at the 20th Congress of the European Hematology Association (abstract S450*).

The decision to undergo HSCT is a complex one in MF, particularly for those patients who are responding to JAK inhibitors. So Dr Shanavas and his colleagues undertook a retrospective, multicenter analysis to determine if there is an association between response to JAK inhibition and HSCT outcome.

The investigators analyzed the outcomes of 100 patients who had a first HSCT for primary MF, post-essential thrombocythemia MF, or post-polycythemia vera MF. Patients had to have exposure to a JAK inhibitor but no history of leukemic transformation prior to taking a JAK inhibitor.

Response criteria

The researchers stratified patients’ JAK1/2 response according to the following criteria:

• Group A: Clinical improvement: Fifty percent or greater reduction in palpable spleen length for spleen palpable by ≥ 10 cm, or complete resolution of splenomegaly for spleen < 10 cm
• Group B: Stable disease: Spleen response not meeting the criteria of clinical improvement
• Group C: A 10% to 19% increase in blasts, new onset of anemia requiring transfusions, or intolerance to treatment due to side effects
• Group D: Progressive disease: New splenomegaly > 5 cm, 100% increase in spleen 5-10 cm, or 50% increase in spleen > 10 cm
• Group E: Leukemic transformation: Bone marrow or circulating blasts ≥ 20%.

Patient and treatment characteristics

Patients were a median age of 59 (range, 32–72). Fifty-seven had primary MF, 21 had post-essential thrombocythemia MF, and 22 had post-polycythemia vera MF. Sixty-two patients had JAK2^V617F-mutated disease, 37 were wild-type, and 1 had unknown JAK status.

The majority of patients had intermediate-2 or high-risk disease according to their DIPSS scores, and 42 had a transplant comorbidity index score of 3 or greater.

Most patients (n=91) had ruxolitinib as their JAK inhibitor, 6 had momelotinib, and 3 had another inhibitor.

The median duration of JAK inhibitor therapy was 5 months (range, 1–36), and 66 patients were on treatment at the time of transplant. Thirty patients had previously discontinued JAK therapy, and the status of 4 was unknown.

In terms of their response to JAK inhibitors, 23 patients were in group A (clinical improvement), 31 in group B (stable disease), 15 in group C (increased blasts/transfusion need/intolerance), 18 in group D (progressive disease), and 13 in group E (leukemic transformation).

Fifty patients received a matched unrelated donor transplant, 36 had a matched sibling donor, and 14 had either a mismatched unrelated donor or a haploidentical transplant.

Fifty-six patients had a reduced-intensity conditioning regimen, and 44 had full intensity. Fifty percent of patients had T-cell depletion prior to transplant.

Outcomes

Patients who stopped JAK inhibitor therapy 6 or more days prior to transplant (n=20) experienced more “withdrawal symptoms”—the return of MF-related symptoms—than patients in whom the interval was less than 6 days (n=46). For the most part, withdrawal symptoms were non-severe in nature.

Two patients had fatal HSCT-related toxicity of venoocclusive disease, 4 had primary graft failure, and 4 had secondary graft failure. Forty-three percent of cytomegalovirus-seropositive patients had reactivation, 6 patients had Epstein-Barr virus reactivation, 6 had adenovirus or human polyomavirus BK infections, and 7 had invasive fungal infections.

Grade 2-4 acute graft-vs-host disease (GVHD) occurred in 37% of patients at day 100, and grade 3-4 occurred in 16%. Chronic GVHD of all grades occurred in 48% of patients, and extensive chronic GVHD occurred in 23%.

The cumulative incidence of relapse at 2 years was 17%, and non-relapse mortality was 28%. Overall survival (OS) was 61%.

“We analyzed this outcome based upon the response to JAK inhibitors,” Dr Shanavas said. “Patients who were deriving clinical improvement, group A, had a superior outcome, with a probability of survival of 91% at 2 years. Patients who had leukemic transformation, group E, had an inferior OS of 32% at 2 years.”

He noted that the outcomes appeared similar in the other 3 groups, so the researchers combined them for further analysis.

“As expected,” he said, “patients who had leukemic transformation had a significantly higher relapse rate than the other groups.”

The researchers then performed a multivariate analysis and found that response to JAK inhibitors, DIPSS score prior to JAK therapy, and donor type had a significant effect on OS.

The team concluded that prior exposure to JAK inhibitors does not have a negative effect on early HSCT outcomes. And actually, patients who undergo HSCT while responding to JAK inhibitors have encouraging outcomes.

*Information in the abstract differs from that presented at the meeting.

HSCT preparation

Photo by Chad McNeeley

VIENNA—Outcomes of hematopoietic stem cell transplant (HSCT) are encouraging in myelofibrosis (MF) patients who respond well to JAK inhibitors, according to researchers.

The group found that patients with the best response to JAK inhibition had a 2-year survival probability of 91% after HSCT, compared to 32% for patients with

leukemic transformation while on a JAK inhibitor.

In addition, receiving a JAK inhibitor until HSCT could prevent the return of MF-related symptoms.

Mohamed Shanavas, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, presented these findings at the 20th Congress of the European Hematology Association (abstract S450*).

The decision to undergo HSCT is a complex one in MF, particularly for those patients who are responding to JAK inhibitors. So Dr Shanavas and his colleagues undertook a retrospective, multicenter analysis to determine if there is an association between response to JAK inhibition and HSCT outcome.

The investigators analyzed the outcomes of 100 patients who had a first HSCT for primary MF, post-essential thrombocythemia MF, or post-polycythemia vera MF. Patients had to have exposure to a JAK inhibitor but no history of leukemic transformation prior to taking a JAK inhibitor.

Response criteria

The researchers stratified patients’ JAK1/2 response according to the following criteria:

• Group A: Clinical improvement: Fifty percent or greater reduction in palpable spleen length for spleen palpable by ≥ 10 cm, or complete resolution of splenomegaly for spleen < 10 cm
• Group B: Stable disease: Spleen response not meeting the criteria of clinical improvement
• Group C: A 10% to 19% increase in blasts, new onset of anemia requiring transfusions, or intolerance to treatment due to side effects
• Group D: Progressive disease: New splenomegaly > 5 cm, 100% increase in spleen 5-10 cm, or 50% increase in spleen > 10 cm
• Group E: Leukemic transformation: Bone marrow or circulating blasts ≥ 20%.

Patient and treatment characteristics

Patients were a median age of 59 (range, 32–72). Fifty-seven had primary MF, 21 had post-essential thrombocythemia MF, and 22 had post-polycythemia vera MF. Sixty-two patients had JAK2^V617F-mutated disease, 37 were wild-type, and 1 had unknown JAK status.

The majority of patients had intermediate-2 or high-risk disease according to their DIPSS scores, and 42 had a transplant comorbidity index score of 3 or greater.

Most patients (n=91) had ruxolitinib as their JAK inhibitor, 6 had momelotinib, and 3 had another inhibitor.

The median duration of JAK inhibitor therapy was 5 months (range, 1–36), and 66 patients were on treatment at the time of transplant. Thirty patients had previously discontinued JAK therapy, and the status of 4 was unknown.

In terms of their response to JAK inhibitors, 23 patients were in group A (clinical improvement), 31 in group B (stable disease), 15 in group C (increased blasts/transfusion need/intolerance), 18 in group D (progressive disease), and 13 in group E (leukemic transformation).

Fifty patients received a matched unrelated donor transplant, 36 had a matched sibling donor, and 14 had either a mismatched unrelated donor or a haploidentical transplant.

Fifty-six patients had a reduced-intensity conditioning regimen, and 44 had full intensity. Fifty percent of patients had T-cell depletion prior to transplant.

Outcomes

Patients who stopped JAK inhibitor therapy 6 or more days prior to transplant (n=20) experienced more “withdrawal symptoms”—the return of MF-related symptoms—than patients in whom the interval was less than 6 days (n=46). For the most part, withdrawal symptoms were non-severe in nature.

Two patients had fatal HSCT-related toxicity of venoocclusive disease, 4 had primary graft failure, and 4 had secondary graft failure. Forty-three percent of cytomegalovirus-seropositive patients had reactivation, 6 patients had Epstein-Barr virus reactivation, 6 had adenovirus or human polyomavirus BK infections, and 7 had invasive fungal infections.

Grade 2-4 acute graft-vs-host disease (GVHD) occurred in 37% of patients at day 100, and grade 3-4 occurred in 16%. Chronic GVHD of all grades occurred in 48% of patients, and extensive chronic GVHD occurred in 23%.

The cumulative incidence of relapse at 2 years was 17%, and non-relapse mortality was 28%. Overall survival (OS) was 61%.

“We analyzed this outcome based upon the response to JAK inhibitors,” Dr Shanavas said. “Patients who were deriving clinical improvement, group A, had a superior outcome, with a probability of survival of 91% at 2 years. Patients who had leukemic transformation, group E, had an inferior OS of 32% at 2 years.”

He noted that the outcomes appeared similar in the other 3 groups, so the researchers combined them for further analysis.

“As expected,” he said, “patients who had leukemic transformation had a significantly higher relapse rate than the other groups.”

The researchers then performed a multivariate analysis and found that response to JAK inhibitors, DIPSS score prior to JAK therapy, and donor type had a significant effect on OS.

The team concluded that prior exposure to JAK inhibitors does not have a negative effect on early HSCT outcomes. And actually, patients who undergo HSCT while responding to JAK inhibitors have encouraging outcomes.

*Information in the abstract differs from that presented at the meeting.