Photo from St. Jude Children’s Research Hospital

Sickle cell disease (SCD) will take center stage at the 2018 ASH Annual Meeting, according to a recent press briefing.

During the briefing, ASH President Alexis A. Thompson, MD, highlighted four “abstracts to watch” that focus on SCD.

These abstracts cover a pilot study of gene therapy, long-term outcomes of haploidentical hematopoietic stem cell transplant (haplo-HSCT), mortality rates in SCD patients prescribed opioids, and outcomes with hydroxyurea (HU) among patients in sub-Saharan Africa.

“These are all quite different aspects of work being done,” said Dr. Thompson, of Ann and Robert H. Lurie Children’s Hospital of Chicago in Illinois.

Gene therapy

In the pilot study of gene therapy (abstract 1023), investigators used a microRNA-adapted short hairpin RNA lentiviral vector targeting BCL11A for autologous gene therapy in SCD patients.

Preclinical research had shown that this approach could induce fetal hemoglobin in human erythroid cells and “largely” attenuate the hematologic effects of SCD in a murine model, according to investigators.

Initial results from the pilot study suggest this approach is feasible in humans as well. In the first patient infused, investigators observed “rapid” induction of fetal hemoglobin and “marked attenuation of hemolysis in the early phase of autologous reconstitution.”

“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said.

Haplo-HSCT

In another study (abstract 162), investigators assessed long-term health-related quality of life in high-risk SCD patients who underwent familial haplo-HSCT.

The patients received myeloablative conditioning and familial haplo-HSCT using CD34 enrichment and mononuclear cell (CD3) addback.

Two years from haplo-HSCT, patients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.

Opioid use

A third study (abstract 315) indicates that opioid use is not associated with in-hospital mortality in SCD patients.

This is interesting in the context of the national opioid epidemic, Dr. Thompson said.

Investigators looked at data from the National Inpatient Sample and found no significant increase in in-hospital mortality in SCD patients from 1998 through 2013. This can be compared to the 350% increase in non-SCD opioid prescription-related deaths from 1999 through 2013.

“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”

HU in sub-Saharan Africa

Dr. Thompson said a fourth study worth watching is REACH (abstract 3), a trial of HU in 635 children in sub-Saharan Africa.

The study provides the first prospective data showing the feasibility, safety, and benefits of HU use in this population, according to investigators.

The findings are “quite encouraging,” Dr. Thompson said.

She added that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.

Photo from St. Jude Children’s Research Hospital

Sickle cell disease (SCD) will take center stage at the 2018 ASH Annual Meeting, according to a recent press briefing.

During the briefing, ASH President Alexis A. Thompson, MD, highlighted four “abstracts to watch” that focus on SCD.

These abstracts cover a pilot study of gene therapy, long-term outcomes of haploidentical hematopoietic stem cell transplant (haplo-HSCT), mortality rates in SCD patients prescribed opioids, and outcomes with hydroxyurea (HU) among patients in sub-Saharan Africa.

“These are all quite different aspects of work being done,” said Dr. Thompson, of Ann and Robert H. Lurie Children’s Hospital of Chicago in Illinois.

Gene therapy

In the pilot study of gene therapy (abstract 1023), investigators used a microRNA-adapted short hairpin RNA lentiviral vector targeting BCL11A for autologous gene therapy in SCD patients.

Preclinical research had shown that this approach could induce fetal hemoglobin in human erythroid cells and “largely” attenuate the hematologic effects of SCD in a murine model, according to investigators.

Initial results from the pilot study suggest this approach is feasible in humans as well. In the first patient infused, investigators observed “rapid” induction of fetal hemoglobin and “marked attenuation of hemolysis in the early phase of autologous reconstitution.”

“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said.

Haplo-HSCT

In another study (abstract 162), investigators assessed long-term health-related quality of life in high-risk SCD patients who underwent familial haplo-HSCT.

The patients received myeloablative conditioning and familial haplo-HSCT using CD34 enrichment and mononuclear cell (CD3) addback.

Two years from haplo-HSCT, patients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.

Opioid use

A third study (abstract 315) indicates that opioid use is not associated with in-hospital mortality in SCD patients.

This is interesting in the context of the national opioid epidemic, Dr. Thompson said.

Investigators looked at data from the National Inpatient Sample and found no significant increase in in-hospital mortality in SCD patients from 1998 through 2013. This can be compared to the 350% increase in non-SCD opioid prescription-related deaths from 1999 through 2013.

“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”

HU in sub-Saharan Africa

Dr. Thompson said a fourth study worth watching is REACH (abstract 3), a trial of HU in 635 children in sub-Saharan Africa.

The study provides the first prospective data showing the feasibility, safety, and benefits of HU use in this population, according to investigators.

The findings are “quite encouraging,” Dr. Thompson said.

She added that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.

Photo from St. Jude Children’s Research Hospital

Sickle cell disease (SCD) will take center stage at the 2018 ASH Annual Meeting, according to a recent press briefing.

During the briefing, ASH President Alexis A. Thompson, MD, highlighted four “abstracts to watch” that focus on SCD.

These abstracts cover a pilot study of gene therapy, long-term outcomes of haploidentical hematopoietic stem cell transplant (haplo-HSCT), mortality rates in SCD patients prescribed opioids, and outcomes with hydroxyurea (HU) among patients in sub-Saharan Africa.

“These are all quite different aspects of work being done,” said Dr. Thompson, of Ann and Robert H. Lurie Children’s Hospital of Chicago in Illinois.

Gene therapy

In the pilot study of gene therapy (abstract 1023), investigators used a microRNA-adapted short hairpin RNA lentiviral vector targeting BCL11A for autologous gene therapy in SCD patients.

Preclinical research had shown that this approach could induce fetal hemoglobin in human erythroid cells and “largely” attenuate the hematologic effects of SCD in a murine model, according to investigators.

Initial results from the pilot study suggest this approach is feasible in humans as well. In the first patient infused, investigators observed “rapid” induction of fetal hemoglobin and “marked attenuation of hemolysis in the early phase of autologous reconstitution.”

“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said.

Haplo-HSCT

In another study (abstract 162), investigators assessed long-term health-related quality of life in high-risk SCD patients who underwent familial haplo-HSCT.

The patients received myeloablative conditioning and familial haplo-HSCT using CD34 enrichment and mononuclear cell (CD3) addback.

Two years from haplo-HSCT, patients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.

Opioid use

A third study (abstract 315) indicates that opioid use is not associated with in-hospital mortality in SCD patients.

This is interesting in the context of the national opioid epidemic, Dr. Thompson said.

Investigators looked at data from the National Inpatient Sample and found no significant increase in in-hospital mortality in SCD patients from 1998 through 2013. This can be compared to the 350% increase in non-SCD opioid prescription-related deaths from 1999 through 2013.

“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”

HU in sub-Saharan Africa

Dr. Thompson said a fourth study worth watching is REACH (abstract 3), a trial of HU in 635 children in sub-Saharan Africa.

The study provides the first prospective data showing the feasibility, safety, and benefits of HU use in this population, according to investigators.

The findings are “quite encouraging,” Dr. Thompson said.

She added that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.

Photo from Penn Medicine

Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.

One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).

Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).

A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.

ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.

Ibrutinib

In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.

Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.

Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.

Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.

These findings are “early and preliminary but very exciting” Dr. Brodsky said.

Checkpoint inhibitors

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.

The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.

CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.

Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.

Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.

There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.

“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”

Tisagenlecleucel follow-up

One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.

The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.

The probability of relapse-free survival was 66% at 12 months and 18 months.

“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).

The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.

HSCT consolidation

Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).

Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.

Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.

There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.

Of the 23 patients who did not undergo another HSCT, eight are still in remission.

“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Photo from Penn Medicine

Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.

One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).

Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).

A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.

ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.

Ibrutinib

In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.

Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.

Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.

Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.

These findings are “early and preliminary but very exciting” Dr. Brodsky said.

Checkpoint inhibitors

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.

The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.

CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.

Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.

Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.

There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.

“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”

Tisagenlecleucel follow-up

One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.

The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.

The probability of relapse-free survival was 66% at 12 months and 18 months.

“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).

The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.

HSCT consolidation

Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).

Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.

Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.

There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.

Of the 23 patients who did not undergo another HSCT, eight are still in remission.

“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Photo from Penn Medicine

Several studies set to be presented at the 2018 ASH Annual Meeting provide new insights regarding chimeric antigen receptor (CAR) T-cell therapies.

One study suggests ibrutinib may enhance CAR T-cell therapy in patients with chronic lymphocytic leukemia (CLL), and another suggests checkpoint inhibitors can augment CAR T-cell therapy in certain patients with B-cell acute lymphoblastic leukemia (ALL).

Two additional studies indicate that responses to tisagenlecleucel are durable in both ALL and diffuse large B-cell lymphoma (DLBCL).

A fifth study suggests hematopoietic stem cell transplant (HSCT) may reduce the risk of relapse after CAR T-cell therapy.

ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland, discussed these studies during a media briefing ahead of the ASH Annual Meeting.

Ibrutinib

In the ibrutinib study (abstract 299), patients received the BTK inhibitor starting 2 weeks prior to leukapheresis and continued until 3 months after treatment with JCAR014.

Data suggest this strategy may improve responses and decrease the incidence of severe cytokine release syndrome in patients with relapsed or refractory CLL.

Responses occurred in 88% of patients who received ibrutinib and 56% of those who did not.

Grade 3-5 cytokine release syndrome occurred in 5 of 19 patients (26%) in the no-ibrutinib cohort and 0 of 17 patients in the ibrutinib cohort.

These findings are “early and preliminary but very exciting” Dr. Brodsky said.

Checkpoint inhibitors

Early results of the checkpoint inhibitor study (abstract 556) suggest that pembrolizumab or nivolumab may augment CD19-directed CAR T-cell therapy.

The 14 patients studied had early CAR T-cell loss, partial response, or no response to CAR T-cell therapy. Thirteen patients had B-cell ALL, and one had B lymphoblastic lymphoma.

CD19-directed CAR T-cell therapy consisted of tisagenlecleucel in four patients and CTL119 in 10. Thirteen patients received pembrolizumab, and one received nivolumab.

Three of six patients who had early B-cell recovery re-established B-cell aplasia with the addition of a checkpoint inhibitor. In two patients, B-cell aplasia persists with ongoing pembrolizumab.

Four patients who did not respond to or relapsed after their initial CAR T-cell therapy had a partial (n=2) or complete response (n=2) with the addition of pembrolizumab.

There were additional partial responses in the remaining four patients. However, one of these patients (with CD19-dim/negative disease) progressed.

“The idea was if you can give pembrolizumab, you can take the brakes off, and maybe you can reinitiate the immune attack,” Dr. Brodsky said.

“[This is a] very small [study with] preliminary data but very exciting that it is safe to give checkpoint inhibitors with CAR T cells, and it may be efficacious at getting the immune response back.”

Tisagenlecleucel follow-up

One of the two tisagenlecleucel updates (abstract 895) consists of data from the ELIANA trial, which includes pediatric and young adult patients with relapsed/refractory ALL.

The overall response rate was 82% (65/79). Of the 65 responders, 29 were still in response at follow-up.

The probability of relapse-free survival was 66% at 12 months and 18 months.

“These are some very fast-growing tumors, and these are refractory, resistant patients, so, as we get further and further out, it’s more encouraging to see that there are durable responses,” Dr. Brodsky said.

The other tisagenlecleucel update (abstract 1684) is from the JULIET trial, which includes adults with relapsed or refractory DLBCL (n=99).

The overall response rate was 54%. The probability of relapse-free survival was 66% at 6 months and 64% at both 12 months and 18 months.

HSCT consolidation

Dr. Brodsky also discussed long-term follow-up from a phase 1/2 trial of SCRI-CAR19v1, a CD19-specific CAR T-cell product, in patients with relapsed/refractory ALL (abstract 967).

Of the 50 evaluable patients, 17 had no history of HSCT prior to CAR T-cell therapy.

Three of the 17 patients did not proceed to HSCT after CAR T-cell therapy, and two of these patients relapsed. Of the 14 patients who did undergo HSCT after CAR T-cell therapy, two relapsed.

There were 33 patients with a prior history of HSCT, and 10 of them had another HSCT after CAR T-cell therapy. Five of them are still alive and in remission.

Of the 23 patients who did not undergo another HSCT, eight are still in remission.

“This study is very small, and it’s retrospective, but it suggests that bone marrow transplant is a good way to consolidate the remission after CAR T-cell therapy,” Dr. Brodsky said.

Researchers from Harvard and Brigham and Women’s Hospital say their study is the first to fully evaluate the link between mutations in sodium glucose co-transporter-1 (SGLT-1)—the gene responsible for absorbing glucose in the gut—and cardiometabolic disease.

The researchers used genetic data from 8,478 participants in the 25-year Atherosclerosis Risk In Communities (ARIC) study. The participants who carried the mutation (6%) had a lower risk of type 2 diabetes, were less obese, had a lower incidence of heart failure, and a lower mortality rate than did those without the mutation, regardless of dietary intake.

The researchers suggest that their findings “open the door to improved therapies” for cardiometabolic diseases.

Researchers from Harvard and Brigham and Women’s Hospital say their study is the first to fully evaluate the link between mutations in sodium glucose co-transporter-1 (SGLT-1)—the gene responsible for absorbing glucose in the gut—and cardiometabolic disease.

The researchers used genetic data from 8,478 participants in the 25-year Atherosclerosis Risk In Communities (ARIC) study. The participants who carried the mutation (6%) had a lower risk of type 2 diabetes, were less obese, had a lower incidence of heart failure, and a lower mortality rate than did those without the mutation, regardless of dietary intake.

The researchers suggest that their findings “open the door to improved therapies” for cardiometabolic diseases.

Researchers from Harvard and Brigham and Women’s Hospital say their study is the first to fully evaluate the link between mutations in sodium glucose co-transporter-1 (SGLT-1)—the gene responsible for absorbing glucose in the gut—and cardiometabolic disease.

The researchers used genetic data from 8,478 participants in the 25-year Atherosclerosis Risk In Communities (ARIC) study. The participants who carried the mutation (6%) had a lower risk of type 2 diabetes, were less obese, had a lower incidence of heart failure, and a lower mortality rate than did those without the mutation, regardless of dietary intake.

The researchers suggest that their findings “open the door to improved therapies” for cardiometabolic diseases.

This episode of the MDedge Daily News features four of the most important stories of 2018 regarding exercise and clinical practice. Physical activity is tied to lower depression risk among older adults, a task force advises behavioral intervention for obese adults, obesity didn’t just happen to society overnight, and the ADA and the EASD come together on a draft consensus statement for managing hyperglycemia in patients with type 2 diabetes.
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Apple Podcasts
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Spotify

This episode of the MDedge Daily News features four of the most important stories of 2018 regarding exercise and clinical practice. Physical activity is tied to lower depression risk among older adults, a task force advises behavioral intervention for obese adults, obesity didn’t just happen to society overnight, and the ADA and the EASD come together on a draft consensus statement for managing hyperglycemia in patients with type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

This episode of the MDedge Daily News features four of the most important stories of 2018 regarding exercise and clinical practice. Physical activity is tied to lower depression risk among older adults, a task force advises behavioral intervention for obese adults, obesity didn’t just happen to society overnight, and the ADA and the EASD come together on a draft consensus statement for managing hyperglycemia in patients with type 2 diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Micrograph showing MM

A retrospective study suggests haploidentical hematopoietic stem cell transplant (haplo-HSCT) is feasible in patients with multiply relapsed or high-risk multiple myeloma (MM).

Investigators said haplo-HSCT produced an “acceptable” rate of non-relapse mortality (NRM)—21% at 1 year—in such patients.

“Our results demonstrate that [haplo-HSCT] can be safely performed in appropriate patients with MM who lack an HLA-matched sibling or unrelated donor,” the investigators wrote in Biology of Blood and Marrow Transplantation.

The research was conducted by Firoozeh Sahebi, MD, of City of Hope Medical Center in Duarte, California, and her colleagues.

The team analyzed data from 96 MM patients who had failed at least one previous autologous transplant and underwent haplo-HSCT between 2008 and 2016.

The patients had a median age of 54.9 (range, 36.6-73.3), and 65.6% were male. At baseline, 37.5% of patients were in very good partial response or better, 31.2% were in partial response, 13.5% had stable disease, and 17.7% had relapsed disease.

The median follow-up was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, and 75% had recovery of platelets by day 60.

Grade 2-4 acute graft-vs-host-disease occurred in 39% of patients by 100 days. Chronic graft-vs-host-disease was seen in 46% of patients at 2 years.

The rate of NRM was 21% at 1 year and 26% at 2 years. The cumulative risk of relapse and progression was 50% at 1 year and 56% at 2 years.

The 2-year progression-free survival (PFS) was 17%, and the 2-year overall survival (OS) was 48%.

In a univariate analysis, bone marrow transplant was associated with significantly better OS than peripheral blood transplant (P=0.001). However, there was no significant difference in PFS between the two.

NRM was lower with bone marrow transplant (P=0.016), and there was a trend toward a higher relapse rate with bone marrow (P=0.083).

The use of cyclophosphamide after transplant was associated with significantly better OS (P=0.009) but not PFS, NRM, or relapse.

Other factors—such as disease status and conditioning regimen—had no significant impact on survival, NRM, or relapse.

The investigators said they had no conflicts of interest related to this research.

Micrograph showing MM

A retrospective study suggests haploidentical hematopoietic stem cell transplant (haplo-HSCT) is feasible in patients with multiply relapsed or high-risk multiple myeloma (MM).

Investigators said haplo-HSCT produced an “acceptable” rate of non-relapse mortality (NRM)—21% at 1 year—in such patients.

“Our results demonstrate that [haplo-HSCT] can be safely performed in appropriate patients with MM who lack an HLA-matched sibling or unrelated donor,” the investigators wrote in Biology of Blood and Marrow Transplantation.

The research was conducted by Firoozeh Sahebi, MD, of City of Hope Medical Center in Duarte, California, and her colleagues.

The team analyzed data from 96 MM patients who had failed at least one previous autologous transplant and underwent haplo-HSCT between 2008 and 2016.

The patients had a median age of 54.9 (range, 36.6-73.3), and 65.6% were male. At baseline, 37.5% of patients were in very good partial response or better, 31.2% were in partial response, 13.5% had stable disease, and 17.7% had relapsed disease.

The median follow-up was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, and 75% had recovery of platelets by day 60.

Grade 2-4 acute graft-vs-host-disease occurred in 39% of patients by 100 days. Chronic graft-vs-host-disease was seen in 46% of patients at 2 years.

The rate of NRM was 21% at 1 year and 26% at 2 years. The cumulative risk of relapse and progression was 50% at 1 year and 56% at 2 years.

The 2-year progression-free survival (PFS) was 17%, and the 2-year overall survival (OS) was 48%.

In a univariate analysis, bone marrow transplant was associated with significantly better OS than peripheral blood transplant (P=0.001). However, there was no significant difference in PFS between the two.

NRM was lower with bone marrow transplant (P=0.016), and there was a trend toward a higher relapse rate with bone marrow (P=0.083).

The use of cyclophosphamide after transplant was associated with significantly better OS (P=0.009) but not PFS, NRM, or relapse.

Other factors—such as disease status and conditioning regimen—had no significant impact on survival, NRM, or relapse.

The investigators said they had no conflicts of interest related to this research.

Micrograph showing MM

A retrospective study suggests haploidentical hematopoietic stem cell transplant (haplo-HSCT) is feasible in patients with multiply relapsed or high-risk multiple myeloma (MM).

Investigators said haplo-HSCT produced an “acceptable” rate of non-relapse mortality (NRM)—21% at 1 year—in such patients.

“Our results demonstrate that [haplo-HSCT] can be safely performed in appropriate patients with MM who lack an HLA-matched sibling or unrelated donor,” the investigators wrote in Biology of Blood and Marrow Transplantation.

The research was conducted by Firoozeh Sahebi, MD, of City of Hope Medical Center in Duarte, California, and her colleagues.

The team analyzed data from 96 MM patients who had failed at least one previous autologous transplant and underwent haplo-HSCT between 2008 and 2016.

The patients had a median age of 54.9 (range, 36.6-73.3), and 65.6% were male. At baseline, 37.5% of patients were in very good partial response or better, 31.2% were in partial response, 13.5% had stable disease, and 17.7% had relapsed disease.

The median follow-up was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, and 75% had recovery of platelets by day 60.

Grade 2-4 acute graft-vs-host-disease occurred in 39% of patients by 100 days. Chronic graft-vs-host-disease was seen in 46% of patients at 2 years.

The rate of NRM was 21% at 1 year and 26% at 2 years. The cumulative risk of relapse and progression was 50% at 1 year and 56% at 2 years.

The 2-year progression-free survival (PFS) was 17%, and the 2-year overall survival (OS) was 48%.

In a univariate analysis, bone marrow transplant was associated with significantly better OS than peripheral blood transplant (P=0.001). However, there was no significant difference in PFS between the two.

NRM was lower with bone marrow transplant (P=0.016), and there was a trend toward a higher relapse rate with bone marrow (P=0.083).

The use of cyclophosphamide after transplant was associated with significantly better OS (P=0.009) but not PFS, NRM, or relapse.

Other factors—such as disease status and conditioning regimen—had no significant impact on survival, NRM, or relapse.

The investigators said they had no conflicts of interest related to this research.

Total knee replacement risk spares after artheroscopic surgery for meniscal tear. Also today, the ADA releases guidelines for type 2 diabetes in children and youth, Nasal glucagon is a viable alternative to intramuscular administration, and draft guidelines advise HIV screening for most teens and adults.

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Total knee replacement risk spares after artheroscopic surgery for meniscal tear. Also today, the ADA releases guidelines for type 2 diabetes in children and youth, Nasal glucagon is a viable alternative to intramuscular administration, and draft guidelines advise HIV screening for most teens and adults.

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Apple Podcasts

Google Podcasts

Spotify

Total knee replacement risk spares after artheroscopic surgery for meniscal tear. Also today, the ADA releases guidelines for type 2 diabetes in children and youth, Nasal glucagon is a viable alternative to intramuscular administration, and draft guidelines advise HIV screening for most teens and adults.

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Apple Podcasts

Google Podcasts

Spotify

Clinical question: Is the combination of aspirin and clopidogrel effective in reducing stroke recurrence?

Background: The risk of recurrent stroke varies from 3% to 15% in the 3 months after a minor ischemic stroke (NIH Stroke Scale score of 3 or less) or high-risk transient ischemic attack (ABCD2 score of 4 or less). Dual-antiplatelet therapy with aspirin and clopidogrel reduces recurrent coronary syndrome; therefore, this strategy can prevent recurrent stroke.

Study design: Prospective, randomized, double-blind, multicenter, placebo-controlled trial.

Setting: 269 sites in 10 countries, mostly in the United States, from May 28, 2010, to Dec. 19, 2017.

Synopsis: The POINT (­Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled 4,881 patients older than 18 years of age randomized to a loading dose of 600 mg of clopidogrel followed by 75 mg per day or placebo, and aspirin 162 mg daily for 5 days followed by 81 mg daily. The primary outcome was the risk of major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes. Major ischemic events were observed in 5.0% receiving dual therapy and in 6.5% of those receiving aspirin alone (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95; P = .02) with most occurring within a week after the initial stroke. Major hemorrhage occurred in only 23 patients (0.9%), most of which were extracranial and nonfatal. One of the main limitations is the difficulty in objectively diagnosing TIAs, accounting for 43% of the patients in the study.

Bottom line: Dual-antiplatelet therapy with aspirin and clopidogrel is beneficial, mainly in the first week after a minor stroke or high-risk TIA with low risk of major bleeding.

Citation: Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25.

Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver.

Clinical question: Is the combination of aspirin and clopidogrel effective in reducing stroke recurrence?

Background: The risk of recurrent stroke varies from 3% to 15% in the 3 months after a minor ischemic stroke (NIH Stroke Scale score of 3 or less) or high-risk transient ischemic attack (ABCD2 score of 4 or less). Dual-antiplatelet therapy with aspirin and clopidogrel reduces recurrent coronary syndrome; therefore, this strategy can prevent recurrent stroke.

Study design: Prospective, randomized, double-blind, multicenter, placebo-controlled trial.

Setting: 269 sites in 10 countries, mostly in the United States, from May 28, 2010, to Dec. 19, 2017.

Synopsis: The POINT (­Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled 4,881 patients older than 18 years of age randomized to a loading dose of 600 mg of clopidogrel followed by 75 mg per day or placebo, and aspirin 162 mg daily for 5 days followed by 81 mg daily. The primary outcome was the risk of major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes. Major ischemic events were observed in 5.0% receiving dual therapy and in 6.5% of those receiving aspirin alone (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95; P = .02) with most occurring within a week after the initial stroke. Major hemorrhage occurred in only 23 patients (0.9%), most of which were extracranial and nonfatal. One of the main limitations is the difficulty in objectively diagnosing TIAs, accounting for 43% of the patients in the study.

Bottom line: Dual-antiplatelet therapy with aspirin and clopidogrel is beneficial, mainly in the first week after a minor stroke or high-risk TIA with low risk of major bleeding.

Citation: Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25.

Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver.

Clinical question: Is the combination of aspirin and clopidogrel effective in reducing stroke recurrence?

Background: The risk of recurrent stroke varies from 3% to 15% in the 3 months after a minor ischemic stroke (NIH Stroke Scale score of 3 or less) or high-risk transient ischemic attack (ABCD2 score of 4 or less). Dual-antiplatelet therapy with aspirin and clopidogrel reduces recurrent coronary syndrome; therefore, this strategy can prevent recurrent stroke.

Study design: Prospective, randomized, double-blind, multicenter, placebo-controlled trial.

Setting: 269 sites in 10 countries, mostly in the United States, from May 28, 2010, to Dec. 19, 2017.

Synopsis: The POINT (­Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled 4,881 patients older than 18 years of age randomized to a loading dose of 600 mg of clopidogrel followed by 75 mg per day or placebo, and aspirin 162 mg daily for 5 days followed by 81 mg daily. The primary outcome was the risk of major ischemic events, including ischemic stroke, myocardial infarction, or death from ischemic vascular causes. Major ischemic events were observed in 5.0% receiving dual therapy and in 6.5% of those receiving aspirin alone (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95; P = .02) with most occurring within a week after the initial stroke. Major hemorrhage occurred in only 23 patients (0.9%), most of which were extracranial and nonfatal. One of the main limitations is the difficulty in objectively diagnosing TIAs, accounting for 43% of the patients in the study.

Bottom line: Dual-antiplatelet therapy with aspirin and clopidogrel is beneficial, mainly in the first week after a minor stroke or high-risk TIA with low risk of major bleeding.

Citation: Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379:215-25.

Dr. Vela-Duarte is assistant professor of neurology at the University of Colorado, Denver.

Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.

Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.

In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.

Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.

However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.

“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.

Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).

Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.

In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.

That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.

As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.

Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.

Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.

Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.

Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”

The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.

The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.

Visit the AGA GI Patient Center for information that you can share with your patients about probiotics. 

SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.

Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.

Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.

In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.

Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.

However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.

“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.

Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).

Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.

In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.

That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.

As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.

Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.

Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.

Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.

Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”

The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.

The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.

Visit the AGA GI Patient Center for information that you can share with your patients about probiotics. 

SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.

Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.

Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.

In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.

Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.

However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.

“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.

Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).

Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.

In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.

That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.

As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.

Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.

Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.

Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.

Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”

The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.

The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.

Visit the AGA GI Patient Center for information that you can share with your patients about probiotics. 

SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.

Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.

Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.

In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.

Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.

However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.

“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.

Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).

Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.

In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.

That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.

As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.

Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.

Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.

Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.

Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”

The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.

The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.

SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.

Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.

Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.

In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.

Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.

However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.

“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.

Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).

Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.

In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.

That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.

As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.

Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.

Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.

Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.

Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”

The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.

The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.

SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.

Two probiotic products containing strains of Lactobacillus rhamnosus failed to prevent moderate-to-severe gastroenteritis in children, according to the results of large, randomized trials published in the New England Journal of Medicine.

Neither probiotic formulation significantly reduced duration of diarrhea or vomiting, or improved endpoints such as daycare absenteeism in the double-blind, placebo-controlled trials, which together included 1,857 infants or children with acute infectious gastroenteritis treated in the United States or Canada.

In one of the two trials, conducted at 10 U.S. pediatric emergency departments, a 5-day course of L. rhamnosus GG did not improve outcomes, versus placebo, according to investigators, led by David Schnadower, MD, of Cincinnati (Ohio) Children’s Hospital Medical Center.

Results of the trial, which comprised 971 children aged 3 months to 4 years, sharply contrast with results of previous studies and meta-analyses suggesting probiotics do improve outcomes in children with acute gastroenteritis.

However, those studies were hampered by small sample sizes, lack of probiotic quality control, and endpoints “of questionable relevance,” among other limitations, according to Dr. Schnadower and his coauthors.

“The rigor of our research design calls into question recommendations to use L. rhamnosus GG in the treatment of children with acute gastroenteritis,” the authors said in their published report.

Moderate to severe gastroenteritis within 14 days of enrollment, the trial’s primary endpoint, occurred in 11.8% of children who received the probiotic, and in 12.6% of those who received placebo (P = .83).

Diarrhea duration was similar, at 49.7 hours and 50.9 hours in the probiotic and placebo groups, respectively (P = .26). Likewise, there were no significant differences in duration of vomiting, daycare absenteeism, or rate of household transmission between the study arms, investigators reported.

In the Canadian trial, which was similar to the U.S. trial but conducted independently, a probiotic product containing L. rhamnosus R0011 and L. helveticus R0052 also showed no significant benefit over placebo in reducing incidence of moderate to severe gastroenteritis within 14 days of enrollment.

That endpoint occurred in 26.1% of children assigned to probiotics, and 24.7% assigned to placebo (P = .72). The trial comprised 886 children 3-48 months presenting to one of six pediatric emergency departments in Canada.

As in the U.S. trial, investigators said there were no significant differences in diarrhea duration, at 52.5 and 55.5 hours in the probiotic and placebo groups, respectively (P = .31). And there were no significant differences in duration of vomiting, unscheduled health care provider visits, or adverse events.

Both trials used a modified Vesikari scale symptom score of 9 or higher (range, 0-20) to define moderate to severe gastroenteritis.

Rather than focusing on a single symptom such as diarrhea, the modified Vesikari scale score shows a “constellation of symptoms” associated with gastroenteritis, according to the Canadian investigators, led by Stephen B. Freedman, MDCM, of the department of pediatrics at Alberta Children’s Hospital and Research Institute, University of Calgary.

Although the use of composite measures has been questioned, the modified Vesikari scale is externally validated and produced consistent findings for individual symptoms, according to the authors. “Analysis of all individual score elements supported the conclusions based on our primary outcome,” they wrote.

Despite the findings, the conclusions about the particular probiotic product evaluated in the trial cannot be generalized to others in the market, according to Dr. Freedman and his colleagues. Other “large, well conducted trials have aroused similar concerns regarding the effectiveness of probiotics for other conditions,” they added. “Nonetheless, there may be specific indications and populations that will benefit from alternative probiotic agents.”

The U.S. study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, among other sources. Dr. Schnadower reported that he received grants from the NICHD and nonfinancial support from iHealth.

The Canadian study was supported by the Canadian Institutes of Health Research, among other sources. Dr. Freedman reported that he received nonfinancial support from Calgary Laboratory Services, Copan Italia, Lallemand Health Solutions, Luminex, and ProvLab Alberta, along with grants from the Canadian Institutes of Health Research and Alberta Children’s Hospital Foundation.

SOURCES: Schnadower D et al. N Engl J Med. 2018 Nov 22;379(21):2002-14; Freedman SB et al. N Engl J Med. 2018 Nov 22;379(21);2015-26.

The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.

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The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.

[email protected]

The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.

[email protected]