Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.

Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.

[email protected]

On Twitter @karioakes

Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.

Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.

[email protected]

On Twitter @karioakes

Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.

Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.

[email protected]

On Twitter @karioakes

Compared with etanercept, secukinumab was associated with significantly faster and greater improvements in skin-specific quality of life among adults with moderate to severe psoriasis, according to a pooled analysis of data from the randomized, multicenter phase III ERASURE and FIXTURE trials.

The findings confirm the clinical superiority of secukinumab and extend prior head-to-head comparisons of this IL-17A inhibitor and etanercept, said Bruce E. Strober, MD, PhD, of the University of Connecticut in Farmington, Conn.

[email protected]

Compared with etanercept, secukinumab was associated with significantly faster and greater improvements in skin-specific quality of life among adults with moderate to severe psoriasis, according to a pooled analysis of data from the randomized, multicenter phase III ERASURE and FIXTURE trials.

The findings confirm the clinical superiority of secukinumab and extend prior head-to-head comparisons of this IL-17A inhibitor and etanercept, said Bruce E. Strober, MD, PhD, of the University of Connecticut in Farmington, Conn.

[email protected]

Compared with etanercept, secukinumab was associated with significantly faster and greater improvements in skin-specific quality of life among adults with moderate to severe psoriasis, according to a pooled analysis of data from the randomized, multicenter phase III ERASURE and FIXTURE trials.

The findings confirm the clinical superiority of secukinumab and extend prior head-to-head comparisons of this IL-17A inhibitor and etanercept, said Bruce E. Strober, MD, PhD, of the University of Connecticut in Farmington, Conn.

[email protected]

Photo by Tiffany D. Nicholson

Smoking by either parent helps promote genetic deletions in children that are associated with the development and progression of acute lymphoblastic leukemia (ALL), according to a study published in Cancer Research.

The strongest associations in this study were found in children whose parents smoked while the children were in utero and during their infancy.

However, the genetic deletions were also noted in the offspring of parents who may have quit smoking even before conception.

The link between ALL and parental smoking has already been established, but this is the first study that points to specific genetic changes in children with ALL, according to study author Adam de Smith, PhD, of the University of California San Francisco.

“With more smoking among the parents, we saw more deletions within the child’s ALL cells at diagnosis,” Dr de smith said.

For this study, he and his colleagues looked at pre-treatment tumor samples from 559 ALL patients.

The team wanted to see if any of the 8 genes that are frequently deleted in ALL patients (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) were missing in the samples.

Questionnaires were given to parents to find out if smoking habits impacted the number of genetic deletions. Data was corroborated by a biomarker in newborns’ blood samples that indicates exposure to maternal smoking during pregnancy.

The researchers found that approximately two-thirds of the tumor samples (n=353) contained at least 1 deletion.

Deletions were considerably more common in children whose mothers had smoked during pregnancy and after birth.

For each 5 cigarettes smoked daily during pregnancy, there was a 22% increase in the number of deletions. For each 5 cigarettes smoked daily during breastfeeding, there was a 74% increase in the number of deletions.

Smoking of 5 cigarettes daily by the mother or father before conception was associated with a 7% to 8% higher number of deletions.

Role of child age and sex

One discovery the researchers found intriguing was the link between the fathers’ pre-conception smoking and their child’s age at diagnosis.

“There was a significant effect on deletion numbers in cases where the patient was age 6 or younger,” Dr de Smith said. “Our results suggest that paternal pre-conception smoking, which is known to cause oxidative damage to sperm DNA, may lead to a higher propensity of deletions in children with earlier-onset ALL.”

“It is also true that some of those fathers who smoked before conception also continue to smoke in the presence of the mother and child, so more research is needed to explain the mechanism of smoking-related damage in all of the time periods of exposure to the child.”

In addition, male children were found to be more sensitive to the effects of maternal smoking, including smoking that occurred pre-conception.

The researchers said this could be explained by the fact that male fetuses grow more rapidly, which leads to increased vulnerability of developing lymphocytes to toxins that cause genetic damage.

“Our study indicates that the more tobacco exposure, the more cumulative DNA damage is evident in the ALL cell,” said study author Joseph Wiemels, PhD, of the University of California San Francisco.

“While causes of ALL are multifactorial—including the inborn genetic makeup of the child, patterns of infection, pesticides, and other environmental exposure—if there was no smoking in the environment, then there would likely be fewer children with the disease. We may add ALL to the long list of diseases impacted by smoking, and, in this case, affecting one of our most vulnerable populations—our children.”

Photo by Tiffany D. Nicholson

Smoking by either parent helps promote genetic deletions in children that are associated with the development and progression of acute lymphoblastic leukemia (ALL), according to a study published in Cancer Research.

The strongest associations in this study were found in children whose parents smoked while the children were in utero and during their infancy.

However, the genetic deletions were also noted in the offspring of parents who may have quit smoking even before conception.

The link between ALL and parental smoking has already been established, but this is the first study that points to specific genetic changes in children with ALL, according to study author Adam de Smith, PhD, of the University of California San Francisco.

“With more smoking among the parents, we saw more deletions within the child’s ALL cells at diagnosis,” Dr de smith said.

For this study, he and his colleagues looked at pre-treatment tumor samples from 559 ALL patients.

The team wanted to see if any of the 8 genes that are frequently deleted in ALL patients (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) were missing in the samples.

Questionnaires were given to parents to find out if smoking habits impacted the number of genetic deletions. Data was corroborated by a biomarker in newborns’ blood samples that indicates exposure to maternal smoking during pregnancy.

The researchers found that approximately two-thirds of the tumor samples (n=353) contained at least 1 deletion.

Deletions were considerably more common in children whose mothers had smoked during pregnancy and after birth.

For each 5 cigarettes smoked daily during pregnancy, there was a 22% increase in the number of deletions. For each 5 cigarettes smoked daily during breastfeeding, there was a 74% increase in the number of deletions.

Smoking of 5 cigarettes daily by the mother or father before conception was associated with a 7% to 8% higher number of deletions.

Role of child age and sex

One discovery the researchers found intriguing was the link between the fathers’ pre-conception smoking and their child’s age at diagnosis.

“There was a significant effect on deletion numbers in cases where the patient was age 6 or younger,” Dr de Smith said. “Our results suggest that paternal pre-conception smoking, which is known to cause oxidative damage to sperm DNA, may lead to a higher propensity of deletions in children with earlier-onset ALL.”

“It is also true that some of those fathers who smoked before conception also continue to smoke in the presence of the mother and child, so more research is needed to explain the mechanism of smoking-related damage in all of the time periods of exposure to the child.”

In addition, male children were found to be more sensitive to the effects of maternal smoking, including smoking that occurred pre-conception.

The researchers said this could be explained by the fact that male fetuses grow more rapidly, which leads to increased vulnerability of developing lymphocytes to toxins that cause genetic damage.

“Our study indicates that the more tobacco exposure, the more cumulative DNA damage is evident in the ALL cell,” said study author Joseph Wiemels, PhD, of the University of California San Francisco.

“While causes of ALL are multifactorial—including the inborn genetic makeup of the child, patterns of infection, pesticides, and other environmental exposure—if there was no smoking in the environment, then there would likely be fewer children with the disease. We may add ALL to the long list of diseases impacted by smoking, and, in this case, affecting one of our most vulnerable populations—our children.”

Photo by Tiffany D. Nicholson

Smoking by either parent helps promote genetic deletions in children that are associated with the development and progression of acute lymphoblastic leukemia (ALL), according to a study published in Cancer Research.

The strongest associations in this study were found in children whose parents smoked while the children were in utero and during their infancy.

However, the genetic deletions were also noted in the offspring of parents who may have quit smoking even before conception.

The link between ALL and parental smoking has already been established, but this is the first study that points to specific genetic changes in children with ALL, according to study author Adam de Smith, PhD, of the University of California San Francisco.

“With more smoking among the parents, we saw more deletions within the child’s ALL cells at diagnosis,” Dr de smith said.

For this study, he and his colleagues looked at pre-treatment tumor samples from 559 ALL patients.

The team wanted to see if any of the 8 genes that are frequently deleted in ALL patients (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) were missing in the samples.

Questionnaires were given to parents to find out if smoking habits impacted the number of genetic deletions. Data was corroborated by a biomarker in newborns’ blood samples that indicates exposure to maternal smoking during pregnancy.

The researchers found that approximately two-thirds of the tumor samples (n=353) contained at least 1 deletion.

Deletions were considerably more common in children whose mothers had smoked during pregnancy and after birth.

For each 5 cigarettes smoked daily during pregnancy, there was a 22% increase in the number of deletions. For each 5 cigarettes smoked daily during breastfeeding, there was a 74% increase in the number of deletions.

Smoking of 5 cigarettes daily by the mother or father before conception was associated with a 7% to 8% higher number of deletions.

Role of child age and sex

One discovery the researchers found intriguing was the link between the fathers’ pre-conception smoking and their child’s age at diagnosis.

“There was a significant effect on deletion numbers in cases where the patient was age 6 or younger,” Dr de Smith said. “Our results suggest that paternal pre-conception smoking, which is known to cause oxidative damage to sperm DNA, may lead to a higher propensity of deletions in children with earlier-onset ALL.”

“It is also true that some of those fathers who smoked before conception also continue to smoke in the presence of the mother and child, so more research is needed to explain the mechanism of smoking-related damage in all of the time periods of exposure to the child.”

In addition, male children were found to be more sensitive to the effects of maternal smoking, including smoking that occurred pre-conception.

The researchers said this could be explained by the fact that male fetuses grow more rapidly, which leads to increased vulnerability of developing lymphocytes to toxins that cause genetic damage.

“Our study indicates that the more tobacco exposure, the more cumulative DNA damage is evident in the ALL cell,” said study author Joseph Wiemels, PhD, of the University of California San Francisco.

“While causes of ALL are multifactorial—including the inborn genetic makeup of the child, patterns of infection, pesticides, and other environmental exposure—if there was no smoking in the environment, then there would likely be fewer children with the disease. We may add ALL to the long list of diseases impacted by smoking, and, in this case, affecting one of our most vulnerable populations—our children.”

SEATTLE – A short course of neoadjuvant therapy could be considered in breast cancer patients with expected delays to resection, while they are awaiting surgery, according to study findings presented at the annual Society of Surgical Oncology Cancer Symposium.

More than half of breast cancer patients who undergo surgical resection as the initial modality will experience delays to surgery of more than 4 weeks. Of this group, more than half of patients receive shorter than standard courses of neoadjuvant therapy (NET), and the patients most likely to benefit were those older than 50 years, with ductal tumors, and the effect was seen in all T stages.

©BluePlanetEarth/thinkstockphotos.com

• How long are patients with operable breast cancer waiting to undergo surgery?

• What is the pattern of use of short-course NET?

• What are the effects of short-course NET on outcomes?

The investigators used the National Cancer Database (NCDB) to identify women who had undergone surgery for stage 1-3 HR+ invasive breast cancer from 2004 to 2013. A total of 530,009 patients met inclusion criteria.

The primary outcomes of the study were time to surgery, the duration of NET, and if the pathologic stage at surgery was lower than clinical stage.

Among patients who did not receive NET, 49.3% underwent surgery within 30 days of diagnosis. More than a third (37.2%) underwent surgery within 60 days of diagnosis, and 13.5% did not have surgery until more than 60 days after their initial diagnosis. A total of 1.8% (9,664) patients underwent NET.

When looking at NET duration, 48% underwent NET for 12 or more weeks, while 52% received NET for less than 12 weeks; 27% received NET for less than 4 weeks, 17% for 4-8 weeks, and 9% for 8-12 weeks.

Downstaging from clinical stage to final pathology stage increased with longer duration of NET. It was 5.5% for less than 1 month on therapy, 9.7% for 1-2 months, and 17.2% for 2-3 months.

“For less than 4 weeks, there was no improvement in N or T downstaging,” said Dr. De Andrade. “As the amount of time on NET increased, it was associated with greater T downstaging. But for N downstaging, it was only at the standard of 12 or more weeks that a difference was seen in nodal downstaging.”

Standard NET of 12 or more weeks was associated with reduced mastectomy rates, but mastectomy rates were not lower in short-course NET.

Among patients undergoing breast conservation therapy, longer duration NET was also associated with a lower risk for re-excision (1-2 months: odds ratio, 0.82, P = .02; 2-3 months: OR, 0.40, P < .001). There was no reduction in re-excision for shorter courses of therapy.

Dr. De Andrade had no disclosures.

SEATTLE – A short course of neoadjuvant therapy could be considered in breast cancer patients with expected delays to resection, while they are awaiting surgery, according to study findings presented at the annual Society of Surgical Oncology Cancer Symposium.

More than half of breast cancer patients who undergo surgical resection as the initial modality will experience delays to surgery of more than 4 weeks. Of this group, more than half of patients receive shorter than standard courses of neoadjuvant therapy (NET), and the patients most likely to benefit were those older than 50 years, with ductal tumors, and the effect was seen in all T stages.

©BluePlanetEarth/thinkstockphotos.com

• How long are patients with operable breast cancer waiting to undergo surgery?

• What is the pattern of use of short-course NET?

• What are the effects of short-course NET on outcomes?

The investigators used the National Cancer Database (NCDB) to identify women who had undergone surgery for stage 1-3 HR+ invasive breast cancer from 2004 to 2013. A total of 530,009 patients met inclusion criteria.

The primary outcomes of the study were time to surgery, the duration of NET, and if the pathologic stage at surgery was lower than clinical stage.

Among patients who did not receive NET, 49.3% underwent surgery within 30 days of diagnosis. More than a third (37.2%) underwent surgery within 60 days of diagnosis, and 13.5% did not have surgery until more than 60 days after their initial diagnosis. A total of 1.8% (9,664) patients underwent NET.

When looking at NET duration, 48% underwent NET for 12 or more weeks, while 52% received NET for less than 12 weeks; 27% received NET for less than 4 weeks, 17% for 4-8 weeks, and 9% for 8-12 weeks.

Downstaging from clinical stage to final pathology stage increased with longer duration of NET. It was 5.5% for less than 1 month on therapy, 9.7% for 1-2 months, and 17.2% for 2-3 months.

“For less than 4 weeks, there was no improvement in N or T downstaging,” said Dr. De Andrade. “As the amount of time on NET increased, it was associated with greater T downstaging. But for N downstaging, it was only at the standard of 12 or more weeks that a difference was seen in nodal downstaging.”

Standard NET of 12 or more weeks was associated with reduced mastectomy rates, but mastectomy rates were not lower in short-course NET.

Among patients undergoing breast conservation therapy, longer duration NET was also associated with a lower risk for re-excision (1-2 months: odds ratio, 0.82, P = .02; 2-3 months: OR, 0.40, P < .001). There was no reduction in re-excision for shorter courses of therapy.

Dr. De Andrade had no disclosures.

SEATTLE – A short course of neoadjuvant therapy could be considered in breast cancer patients with expected delays to resection, while they are awaiting surgery, according to study findings presented at the annual Society of Surgical Oncology Cancer Symposium.

More than half of breast cancer patients who undergo surgical resection as the initial modality will experience delays to surgery of more than 4 weeks. Of this group, more than half of patients receive shorter than standard courses of neoadjuvant therapy (NET), and the patients most likely to benefit were those older than 50 years, with ductal tumors, and the effect was seen in all T stages.

©BluePlanetEarth/thinkstockphotos.com

• How long are patients with operable breast cancer waiting to undergo surgery?

• What is the pattern of use of short-course NET?

• What are the effects of short-course NET on outcomes?

The investigators used the National Cancer Database (NCDB) to identify women who had undergone surgery for stage 1-3 HR+ invasive breast cancer from 2004 to 2013. A total of 530,009 patients met inclusion criteria.

The primary outcomes of the study were time to surgery, the duration of NET, and if the pathologic stage at surgery was lower than clinical stage.

Among patients who did not receive NET, 49.3% underwent surgery within 30 days of diagnosis. More than a third (37.2%) underwent surgery within 60 days of diagnosis, and 13.5% did not have surgery until more than 60 days after their initial diagnosis. A total of 1.8% (9,664) patients underwent NET.

When looking at NET duration, 48% underwent NET for 12 or more weeks, while 52% received NET for less than 12 weeks; 27% received NET for less than 4 weeks, 17% for 4-8 weeks, and 9% for 8-12 weeks.

Downstaging from clinical stage to final pathology stage increased with longer duration of NET. It was 5.5% for less than 1 month on therapy, 9.7% for 1-2 months, and 17.2% for 2-3 months.

“For less than 4 weeks, there was no improvement in N or T downstaging,” said Dr. De Andrade. “As the amount of time on NET increased, it was associated with greater T downstaging. But for N downstaging, it was only at the standard of 12 or more weeks that a difference was seen in nodal downstaging.”

Standard NET of 12 or more weeks was associated with reduced mastectomy rates, but mastectomy rates were not lower in short-course NET.

Among patients undergoing breast conservation therapy, longer duration NET was also associated with a lower risk for re-excision (1-2 months: odds ratio, 0.82, P = .02; 2-3 months: OR, 0.40, P < .001). There was no reduction in re-excision for shorter courses of therapy.

Dr. De Andrade had no disclosures.

WASHINGTON – U.S. heart teams have used the mitral valve transcatheter clip repair device for fixing leaky mitral valves exactly the way it was designed to be used once the device hit the U.S. market in 2013.

In the first review of periprocedural and 1-year outcomes of U.S. patients treated with the MitraClip repair device and entered in the national device registry, the results showed “acute effectiveness and safety of transcatheter mitral valve repair,” Paul Sorajja, MD, said at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

WASHINGTON – U.S. heart teams have used the mitral valve transcatheter clip repair device for fixing leaky mitral valves exactly the way it was designed to be used once the device hit the U.S. market in 2013.

In the first review of periprocedural and 1-year outcomes of U.S. patients treated with the MitraClip repair device and entered in the national device registry, the results showed “acute effectiveness and safety of transcatheter mitral valve repair,” Paul Sorajja, MD, said at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

WASHINGTON – U.S. heart teams have used the mitral valve transcatheter clip repair device for fixing leaky mitral valves exactly the way it was designed to be used once the device hit the U.S. market in 2013.

In the first review of periprocedural and 1-year outcomes of U.S. patients treated with the MitraClip repair device and entered in the national device registry, the results showed “acute effectiveness and safety of transcatheter mitral valve repair,” Paul Sorajja, MD, said at the annual meeting of the American College of Cardiology.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

ORLANDO – For patients who have received hematopoietic cell transplants, a rhinovirus infection can become much more than a cold.

“It holds true that rhinovirus is just as likely to be associated with mortality as are other respiratory viruses” among HCT recipients, Alpana Waghmare, MD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

In a new retrospective study, Dr. Waghmare and her coinvestigators found that the median time for a rhinovirus infection to progress from an upper to a lower respiratory tract infection was about 2 weeks among post-HCT patients.

Clinical and demographic risk factors for progression to lower respiratory tract infection included higher levels of steroid use (2 mg/kg per day or more) before developing the upper respiratory infection, a low white blood cell count, and a low monocyte count, said Dr. Waghmare, an infectious disease specialist and professor of pediatrics at the University of Washington, Seattle.

Of 3,445 HCT patients treated at the university center during the 6-year study, 732 patients (21%) were positive for human rhinovirus. Patients were classified as having upper respiratory infections if they had a PCR-positive nasal swab.

Patients were classed in one of three categories for potential lower respiratory infections: Proven lower respiratory infections were those detected by bronchoalveolar lavage or biopsy in patients who had a new radiographic abnormality. Probable lower respiratory infections were those with positive findings on bronchoalveolar lavage or biopsy but without radiographic changes. In possible lower respiratory infections, patients had upper tract virus detected on nasal swabs but did have a new radiographic abnormality.

Among the patients positive for human rhinovirus, 85% (665 patients) presented with upper respiratory infections and 15% (117 patients) with lower respiratory tract infections. By day 90, 16% of patients progressed from upper to lower respiratory tract infections. The median time to progression was 13.5 days. Progression to proven lower respiratory tract infection affected 5% of the HCT recipients.

In multivariable analytic models, a minimum white blood cell count of 1,000 or less was associated with a hazard ratio (HR) of 2.21 for progression to lower respiratory tract infection. A minimum monocyte count of 1,000 or less was associated with a HR of 3.66 for progression to lower respiratory tract infection.

The model also found a HR of 3.37 for lower respiratory tract infection with steroid use of 2 mg/kg per day or more. The patient’s conditioning regimen and donor type were not significantly associated with risk of progression to lower respiratory infection.

Viral copathogens, prior respiratory virus episodes, and the duration of time since HCT were not associated with risk of progress to lower respiratory infections. Neither were patient age, baseline lung function, and the year the transplant occurred.

“These data provide an initial framework for patient risk stratification and the development of rational prevention and treatment strategies in HCT recipients,” she said.

Dr. Waghmare reported receiving research funding from Aviragen, the maker of vapendavir, an investigational drug for human rhinovirus infection, and Gilead Sciences.

[email protected]

On Twitter @karioakes

ORLANDO – For patients who have received hematopoietic cell transplants, a rhinovirus infection can become much more than a cold.

“It holds true that rhinovirus is just as likely to be associated with mortality as are other respiratory viruses” among HCT recipients, Alpana Waghmare, MD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

In a new retrospective study, Dr. Waghmare and her coinvestigators found that the median time for a rhinovirus infection to progress from an upper to a lower respiratory tract infection was about 2 weeks among post-HCT patients.

Clinical and demographic risk factors for progression to lower respiratory tract infection included higher levels of steroid use (2 mg/kg per day or more) before developing the upper respiratory infection, a low white blood cell count, and a low monocyte count, said Dr. Waghmare, an infectious disease specialist and professor of pediatrics at the University of Washington, Seattle.

Of 3,445 HCT patients treated at the university center during the 6-year study, 732 patients (21%) were positive for human rhinovirus. Patients were classified as having upper respiratory infections if they had a PCR-positive nasal swab.

Patients were classed in one of three categories for potential lower respiratory infections: Proven lower respiratory infections were those detected by bronchoalveolar lavage or biopsy in patients who had a new radiographic abnormality. Probable lower respiratory infections were those with positive findings on bronchoalveolar lavage or biopsy but without radiographic changes. In possible lower respiratory infections, patients had upper tract virus detected on nasal swabs but did have a new radiographic abnormality.

Among the patients positive for human rhinovirus, 85% (665 patients) presented with upper respiratory infections and 15% (117 patients) with lower respiratory tract infections. By day 90, 16% of patients progressed from upper to lower respiratory tract infections. The median time to progression was 13.5 days. Progression to proven lower respiratory tract infection affected 5% of the HCT recipients.

In multivariable analytic models, a minimum white blood cell count of 1,000 or less was associated with a hazard ratio (HR) of 2.21 for progression to lower respiratory tract infection. A minimum monocyte count of 1,000 or less was associated with a HR of 3.66 for progression to lower respiratory tract infection.

The model also found a HR of 3.37 for lower respiratory tract infection with steroid use of 2 mg/kg per day or more. The patient’s conditioning regimen and donor type were not significantly associated with risk of progression to lower respiratory infection.

Viral copathogens, prior respiratory virus episodes, and the duration of time since HCT were not associated with risk of progress to lower respiratory infections. Neither were patient age, baseline lung function, and the year the transplant occurred.

“These data provide an initial framework for patient risk stratification and the development of rational prevention and treatment strategies in HCT recipients,” she said.

Dr. Waghmare reported receiving research funding from Aviragen, the maker of vapendavir, an investigational drug for human rhinovirus infection, and Gilead Sciences.

[email protected]

On Twitter @karioakes

ORLANDO – For patients who have received hematopoietic cell transplants, a rhinovirus infection can become much more than a cold.

“It holds true that rhinovirus is just as likely to be associated with mortality as are other respiratory viruses” among HCT recipients, Alpana Waghmare, MD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

In a new retrospective study, Dr. Waghmare and her coinvestigators found that the median time for a rhinovirus infection to progress from an upper to a lower respiratory tract infection was about 2 weeks among post-HCT patients.

Clinical and demographic risk factors for progression to lower respiratory tract infection included higher levels of steroid use (2 mg/kg per day or more) before developing the upper respiratory infection, a low white blood cell count, and a low monocyte count, said Dr. Waghmare, an infectious disease specialist and professor of pediatrics at the University of Washington, Seattle.

Of 3,445 HCT patients treated at the university center during the 6-year study, 732 patients (21%) were positive for human rhinovirus. Patients were classified as having upper respiratory infections if they had a PCR-positive nasal swab.

Patients were classed in one of three categories for potential lower respiratory infections: Proven lower respiratory infections were those detected by bronchoalveolar lavage or biopsy in patients who had a new radiographic abnormality. Probable lower respiratory infections were those with positive findings on bronchoalveolar lavage or biopsy but without radiographic changes. In possible lower respiratory infections, patients had upper tract virus detected on nasal swabs but did have a new radiographic abnormality.

Among the patients positive for human rhinovirus, 85% (665 patients) presented with upper respiratory infections and 15% (117 patients) with lower respiratory tract infections. By day 90, 16% of patients progressed from upper to lower respiratory tract infections. The median time to progression was 13.5 days. Progression to proven lower respiratory tract infection affected 5% of the HCT recipients.

In multivariable analytic models, a minimum white blood cell count of 1,000 or less was associated with a hazard ratio (HR) of 2.21 for progression to lower respiratory tract infection. A minimum monocyte count of 1,000 or less was associated with a HR of 3.66 for progression to lower respiratory tract infection.

The model also found a HR of 3.37 for lower respiratory tract infection with steroid use of 2 mg/kg per day or more. The patient’s conditioning regimen and donor type were not significantly associated with risk of progression to lower respiratory infection.

Viral copathogens, prior respiratory virus episodes, and the duration of time since HCT were not associated with risk of progress to lower respiratory infections. Neither were patient age, baseline lung function, and the year the transplant occurred.

“These data provide an initial framework for patient risk stratification and the development of rational prevention and treatment strategies in HCT recipients,” she said.

Dr. Waghmare reported receiving research funding from Aviragen, the maker of vapendavir, an investigational drug for human rhinovirus infection, and Gilead Sciences.

[email protected]

On Twitter @karioakes

Treatment with the anti-PD-L1 cancer immunotherapy atezolizumab produced a durable clinical benefit in patients with metastatic triple-negative breast cancer who responded to treatment, according to results from a phase I study.

Overall survival (OS) rates were 41% at 1 year and 22% at both year 2 and year 3. Patients with PD-L1 on 5% or more of tumor-infiltrating immune cells (IC2/3) achieved even better clinical outcomes: Their OS rates at 1, 2, and 3 years were 45%, 28%, and 28%.

The findings from this early phase I trial, which were presented at the annual meeting of the American Association for Cancer Research, also demonstrated that response rates were higher in the first-line setting, and an exploratory biomarker analysis suggested that higher CD8 T cell and tumor-infiltrating lymphocyte counts also contributed to a better response.

“We have no targeted therapy at the moment for triple-negative breast cancer,” said study lead author Dr. Peter Schmid, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London, during a media briefing. “The treatment we have is chemotherapy, and most patients develop resistance relatively quickly.”

Dr. Schmid noted that the median survival for these patients is still relatively short – about 9-12 months – so, the data from this trial need to be seen in that context.

“On the other hand, triple-negative breast cancer is probably the best subtype of breast cancer in terms of selecting patients for immune therapy,” said Dr. Schmid. “This is based on a high degree of genetic instability, a high rate of mutations, higher levels of PD-L1 expression, and tumor infiltrating lymphocytes inside the tumor.”

Atezolizumab is a humanized monoclonal antibody that disrupts the PD pathway, inhibits the binding of PD-L1 to PD-1 and B7.1, and, in doing so, restores tumor-specific T-cell immunity.

In this study, Dr Schmid and colleagues recruited patients with metastatic triple-negative breast cancer to one of the expansion cohorts of a phase I trial. A total of 112 patients were evaluable for response. Of this group, 19 received atezolizumab as first-line treatment, and 93 had received at least two lines of prior therapy.

Atezolizumab was administered every 3 weeks at 15 mg/kg or 20 mg/kg, and the level of PD-L1 expression on tumor-infiltrating immune cells was evaluated. The primary endpoint of the study was safety, with overall response rate, duration of response, and progression-free survival as key secondary endpoints.

The 1- and 2-year overall survival rates for responders were 100%, but that dropped to 33% and 11%, respectively, for nonresponders. Of the 11 responders, 5 received atezolizumab as first-line therapy, while 9 had high PD-L1 expression (IC2/3).

For patients who received atezolizumab in the first-line setting, 1-year overall survival was 63%, and 2-year overall survival was 47%. The rates were lower for second-line and beyond; 37% and 18%, respectively.

For IC2/3 patients, 1-year overall survival was 45%, compared with 37% for those with low to no PD-L1 expression (IC0/1).

Only 11% of patients experienced treatment-related grade 3 or greater adverse events, and side effects led to treatment discontinuation in 3% of patients.

A key message was that the duration of response had a median of 21 months, and that is significant in this disease setting, explained Dr. Schmid. Another important point was that “overall survival was significantly longer that what we see with chemotherapy.”

Genentech funded the study. Dr Schmid’s spouse is a consultant to Roche/Genentech.

Treatment with the anti-PD-L1 cancer immunotherapy atezolizumab produced a durable clinical benefit in patients with metastatic triple-negative breast cancer who responded to treatment, according to results from a phase I study.

Overall survival (OS) rates were 41% at 1 year and 22% at both year 2 and year 3. Patients with PD-L1 on 5% or more of tumor-infiltrating immune cells (IC2/3) achieved even better clinical outcomes: Their OS rates at 1, 2, and 3 years were 45%, 28%, and 28%.

The findings from this early phase I trial, which were presented at the annual meeting of the American Association for Cancer Research, also demonstrated that response rates were higher in the first-line setting, and an exploratory biomarker analysis suggested that higher CD8 T cell and tumor-infiltrating lymphocyte counts also contributed to a better response.

“We have no targeted therapy at the moment for triple-negative breast cancer,” said study lead author Dr. Peter Schmid, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London, during a media briefing. “The treatment we have is chemotherapy, and most patients develop resistance relatively quickly.”

Dr. Schmid noted that the median survival for these patients is still relatively short – about 9-12 months – so, the data from this trial need to be seen in that context.

“On the other hand, triple-negative breast cancer is probably the best subtype of breast cancer in terms of selecting patients for immune therapy,” said Dr. Schmid. “This is based on a high degree of genetic instability, a high rate of mutations, higher levels of PD-L1 expression, and tumor infiltrating lymphocytes inside the tumor.”

Atezolizumab is a humanized monoclonal antibody that disrupts the PD pathway, inhibits the binding of PD-L1 to PD-1 and B7.1, and, in doing so, restores tumor-specific T-cell immunity.

In this study, Dr Schmid and colleagues recruited patients with metastatic triple-negative breast cancer to one of the expansion cohorts of a phase I trial. A total of 112 patients were evaluable for response. Of this group, 19 received atezolizumab as first-line treatment, and 93 had received at least two lines of prior therapy.

Atezolizumab was administered every 3 weeks at 15 mg/kg or 20 mg/kg, and the level of PD-L1 expression on tumor-infiltrating immune cells was evaluated. The primary endpoint of the study was safety, with overall response rate, duration of response, and progression-free survival as key secondary endpoints.

The 1- and 2-year overall survival rates for responders were 100%, but that dropped to 33% and 11%, respectively, for nonresponders. Of the 11 responders, 5 received atezolizumab as first-line therapy, while 9 had high PD-L1 expression (IC2/3).

For patients who received atezolizumab in the first-line setting, 1-year overall survival was 63%, and 2-year overall survival was 47%. The rates were lower for second-line and beyond; 37% and 18%, respectively.

For IC2/3 patients, 1-year overall survival was 45%, compared with 37% for those with low to no PD-L1 expression (IC0/1).

Only 11% of patients experienced treatment-related grade 3 or greater adverse events, and side effects led to treatment discontinuation in 3% of patients.

A key message was that the duration of response had a median of 21 months, and that is significant in this disease setting, explained Dr. Schmid. Another important point was that “overall survival was significantly longer that what we see with chemotherapy.”

Genentech funded the study. Dr Schmid’s spouse is a consultant to Roche/Genentech.

Treatment with the anti-PD-L1 cancer immunotherapy atezolizumab produced a durable clinical benefit in patients with metastatic triple-negative breast cancer who responded to treatment, according to results from a phase I study.

Overall survival (OS) rates were 41% at 1 year and 22% at both year 2 and year 3. Patients with PD-L1 on 5% or more of tumor-infiltrating immune cells (IC2/3) achieved even better clinical outcomes: Their OS rates at 1, 2, and 3 years were 45%, 28%, and 28%.

The findings from this early phase I trial, which were presented at the annual meeting of the American Association for Cancer Research, also demonstrated that response rates were higher in the first-line setting, and an exploratory biomarker analysis suggested that higher CD8 T cell and tumor-infiltrating lymphocyte counts also contributed to a better response.

“We have no targeted therapy at the moment for triple-negative breast cancer,” said study lead author Dr. Peter Schmid, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London, during a media briefing. “The treatment we have is chemotherapy, and most patients develop resistance relatively quickly.”

Dr. Schmid noted that the median survival for these patients is still relatively short – about 9-12 months – so, the data from this trial need to be seen in that context.

“On the other hand, triple-negative breast cancer is probably the best subtype of breast cancer in terms of selecting patients for immune therapy,” said Dr. Schmid. “This is based on a high degree of genetic instability, a high rate of mutations, higher levels of PD-L1 expression, and tumor infiltrating lymphocytes inside the tumor.”

Atezolizumab is a humanized monoclonal antibody that disrupts the PD pathway, inhibits the binding of PD-L1 to PD-1 and B7.1, and, in doing so, restores tumor-specific T-cell immunity.

In this study, Dr Schmid and colleagues recruited patients with metastatic triple-negative breast cancer to one of the expansion cohorts of a phase I trial. A total of 112 patients were evaluable for response. Of this group, 19 received atezolizumab as first-line treatment, and 93 had received at least two lines of prior therapy.

Atezolizumab was administered every 3 weeks at 15 mg/kg or 20 mg/kg, and the level of PD-L1 expression on tumor-infiltrating immune cells was evaluated. The primary endpoint of the study was safety, with overall response rate, duration of response, and progression-free survival as key secondary endpoints.

The 1- and 2-year overall survival rates for responders were 100%, but that dropped to 33% and 11%, respectively, for nonresponders. Of the 11 responders, 5 received atezolizumab as first-line therapy, while 9 had high PD-L1 expression (IC2/3).

For patients who received atezolizumab in the first-line setting, 1-year overall survival was 63%, and 2-year overall survival was 47%. The rates were lower for second-line and beyond; 37% and 18%, respectively.

For IC2/3 patients, 1-year overall survival was 45%, compared with 37% for those with low to no PD-L1 expression (IC0/1).

Only 11% of patients experienced treatment-related grade 3 or greater adverse events, and side effects led to treatment discontinuation in 3% of patients.

A key message was that the duration of response had a median of 21 months, and that is significant in this disease setting, explained Dr. Schmid. Another important point was that “overall survival was significantly longer that what we see with chemotherapy.”

Genentech funded the study. Dr Schmid’s spouse is a consultant to Roche/Genentech.

ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.

Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.

The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.

All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.

“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”

The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.

Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.

The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.

At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.

At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.

Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.

Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.

Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.

The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.

Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.

[email protected]

On Twitter @Alz_gal

ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.

Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.

The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.

All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.

“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”

The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.

Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.

The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.

At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.

At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.

Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.

Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.

Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.

The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.

Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.

[email protected]

On Twitter @Alz_gal

ORLANDO – About 80% of children with growth disorders will attain their expected normal adult height if adequately treated with growth hormone, a large observational study has determined.

Somatropin recombinant human growth hormone seemed most effective for patients with growth hormone deficiency, idiopathic short stature, and for those who were born small for gestational age. Patients who had Turner syndrome or a homeobox-deficiency gene didn’t do quite as well, although most did still improve their final height.

The Genetics and Neuroendocrinology of Short Stature International Study (GENESIS) followed more than 22,000 children who were treated in 30 countries from 1999 to 2015.

All of the patients were treated with somatropin recombinant human growth hormone (Humatrope). Eli Lilly, which makes the medication, sponsored the study and presented the results during a poster session at the annual meeting of the Endocrine Society. Representatives at the poster declined to discuss results with the media during the open session.

“The results speak for themselves,” said Cheri Deal, MD, PhD, of the University of Montreal, Quebec, one of the presenting authors. “It’s an incredible story.”

The GENESIS cohort comprised more than 22,000 children who were treated for a variety of growth disorders at 827 international sites.

Subanalyses have been published, but this is the first release of the data on 5,076 patients with full follow-up. Most of the patients (61%) received the medication for growth hormone deficiency. Other indications were Turner syndrome (14%), idiopathic short stature (11%), short-stature homeobox-containing gene deficiency (3%), small for gestational age (5%), and chronic renal insufficiency (0.3%). Other diagnoses, plus unknown causes, made up the remainder of the diagnoses.

The investigators, led by Christopher J. Child, PhD, an Eli Lilly scientist, split the cohort into diagnostic groups and treatment subgroups: those who attained normal adult height, those who attained normal adult height with at least 4 years of treatment, and those who gained normal adult height who started treatment at younger than 10 years of age.

At baseline, those with growth hormone deficiency were a mean of 11 years old; their height was a mean of 2.4 standard deviations (SDS) below normal. They received a mean of 6 years of treatment; 86% achieved a normal adult height, with an overall gain of 1.39 SDS. Those who started somatropin before age 10 years made bigger gains. The final height gain was 1.78 SDS after a mean of 9.5 years of treatment.

At baseline, those with idiopathic short stature were a mean of 12 years old; their mean height was 2.3 SDS below normal. They received a mean of 4.7 years of treatment; 82% achieved normal height, with a gain of 1.1 SDS. Starting somatropin at a younger age (mean 8 years) improved outcomes slightly, with a final height gain of 1.6 SDS after 8 years of treatment.

Patients with Turner syndrome were a mean of 10 years when they started treatment; their mean height was 2.65 SDS below normal. They received a mean of 6.4 years of treatment; 66% achieved normal adult height, with a mean height gain of 0.95 SDS. Early treatment didn’t alter outcomes much in this group. After a mean of 8.5 years of treatment, 65% achieved normal height, with a height gain of 0.84 SDS.

Patients with a short-stature homeobox-containing gene deficiency were a mean of 11 years when they started treatment. At that time, their height was a mean of 2.36 SDS below normal. They were treated for a mean of 4.7 years; 76% achieved a normal adult height, with a mean gain of 0.86 SDS. Early treatment did improve outcomes a bit. After a mean treatment time of 7 years, 78% gained normal adult height, with a height gain of 0.84 SDS.

Children who were small for gestational age started treatment when they were a mean of 10.5 years. At that time, their mean height was 2.57 SDS below normal. They were treated for a mean of 5.4 years; 78% attained a normal adult height, with a mean gain of 1.1 SDS. Early treatment improved outcomes. After a mean treatment time of 7.8 years, 81% achieved normal adult height, with a mean gain of 1.41 SDS.

The less-robust gains seen in the children with genetically influenced growth disorders “wasn’t unexpected” and is in line with what has been observed in a number of clinical trials, the investigators said.

Eli Lilly manufactures the somatropin product used in the study, and it sponsored the study. Dr. Child is an employee of the company. Dr. Deal did not have any financial disclosures.

[email protected]

On Twitter @Alz_gal

SAN DIEGO – Incorporating pharmacists into primary care offices has the potential to significantly impact patient care and save health care costs, according to Hae Mi Choe, PharmD.

Drug-related morbidity in the United States costs an estimated $290 billion annually, or about 13% of total health care expenditures, said Dr. Choe, associate dean at the University of Michigan College of Pharmacy and director of pharmacy innovations and partnerships at the University of Michigan Medical Group, Ann Arbor.

[email protected]

SAN DIEGO – Incorporating pharmacists into primary care offices has the potential to significantly impact patient care and save health care costs, according to Hae Mi Choe, PharmD.

Drug-related morbidity in the United States costs an estimated $290 billion annually, or about 13% of total health care expenditures, said Dr. Choe, associate dean at the University of Michigan College of Pharmacy and director of pharmacy innovations and partnerships at the University of Michigan Medical Group, Ann Arbor.

[email protected]

SAN DIEGO – Incorporating pharmacists into primary care offices has the potential to significantly impact patient care and save health care costs, according to Hae Mi Choe, PharmD.

Drug-related morbidity in the United States costs an estimated $290 billion annually, or about 13% of total health care expenditures, said Dr. Choe, associate dean at the University of Michigan College of Pharmacy and director of pharmacy innovations and partnerships at the University of Michigan Medical Group, Ann Arbor.

[email protected]

NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

[email protected]

On Twitter @mitchelzoler

NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

[email protected]

On Twitter @mitchelzoler

NEW YORK – The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

[email protected]

On Twitter @mitchelzoler