Caleb Rans

Long-term genetically low levels of LDL cholesterol, by means of functional variants in the PCSK9 gene, were associated with a reduced risk of CV mortality, but not all-cause mortality, in a large cohort of individuals.

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“We tested the hypothesis that genetically low LDL cholesterol due to PCSK9 [proprotein convertase subtilisin/kexin type 9] variation is causally associated with low cardiovascular and all-cause mortality in a general population of Northern European ancestry,” wrote Marianne Benn, MD, DMSc, and colleagues. The findings were published in the Journal of the American College of Cardiology.

The researchers conducted a large-scale genetic analysis of 109,566 persons from the Copenhagen City Heart Study and Copenhagen General Population Study. In addition, the team included a validation cohort of 431,043 individuals from the UK Biobank.

The median duration of follow-up was 10 years (0-42 years), and the median age at study entry was 57 years.

Study participants were genotyped for several PCSK9 variants and a weighted allele score based the effects of LDL cholesterol, individual allele frequency, and number of variant alleles was calculated for each subject.

Weighted scores were categorized into five stepwise noncontinuous score ranges, with lower levels of LDL cholesterol linked to higher allele scores.

After analysis, the researchers found that a growing number of PCSK9 alleles were associated with lower levels of LDL cholesterol up to 0.61 mmol/L (P for trend less than .001) and reduced CV mortality (P = .001), but not with reduced all-cause mortality (P = .11).

“Our genetic data did not show a reduction in risk of all-cause mortality, and only showed a reduction in risk of all-cause mortality in statin trials and not in the PCSK9-inhibitor trials meta-analyzed,” the researchers wrote. “This may be explained by the low frequency of cardiovascular disease in the 2 populations studied,” they explained.

One key limitation was the homogeneous makeup of the study population. Dr. Benn and colleagues acknowledged this could limit the generalizability of the results.

“Long-term LDL cholesterol treatment (e.g., with PCSK9 inhibitors), may translate into reductions in cardiovascular mortality,” they concluded.

The study was supported by the Danish Council for Independent Research, Medical Sciences, Johan Boserup, and the Lise Boserup’s Fund. The authors reported no conflicts of interest.

SOURCE: Benn M et al. JACC. 2019 Jun 17. doi: 10.1016/j.jacc.2019.03.517

Long-term genetically low levels of LDL cholesterol, by means of functional variants in the PCSK9 gene, were associated with a reduced risk of CV mortality, but not all-cause mortality, in a large cohort of individuals.

ktsimage/Thinkstock

“We tested the hypothesis that genetically low LDL cholesterol due to PCSK9 [proprotein convertase subtilisin/kexin type 9] variation is causally associated with low cardiovascular and all-cause mortality in a general population of Northern European ancestry,” wrote Marianne Benn, MD, DMSc, and colleagues. The findings were published in the Journal of the American College of Cardiology.

The researchers conducted a large-scale genetic analysis of 109,566 persons from the Copenhagen City Heart Study and Copenhagen General Population Study. In addition, the team included a validation cohort of 431,043 individuals from the UK Biobank.

The median duration of follow-up was 10 years (0-42 years), and the median age at study entry was 57 years.

Study participants were genotyped for several PCSK9 variants and a weighted allele score based the effects of LDL cholesterol, individual allele frequency, and number of variant alleles was calculated for each subject.

Weighted scores were categorized into five stepwise noncontinuous score ranges, with lower levels of LDL cholesterol linked to higher allele scores.

After analysis, the researchers found that a growing number of PCSK9 alleles were associated with lower levels of LDL cholesterol up to 0.61 mmol/L (P for trend less than .001) and reduced CV mortality (P = .001), but not with reduced all-cause mortality (P = .11).

“Our genetic data did not show a reduction in risk of all-cause mortality, and only showed a reduction in risk of all-cause mortality in statin trials and not in the PCSK9-inhibitor trials meta-analyzed,” the researchers wrote. “This may be explained by the low frequency of cardiovascular disease in the 2 populations studied,” they explained.

One key limitation was the homogeneous makeup of the study population. Dr. Benn and colleagues acknowledged this could limit the generalizability of the results.

“Long-term LDL cholesterol treatment (e.g., with PCSK9 inhibitors), may translate into reductions in cardiovascular mortality,” they concluded.

The study was supported by the Danish Council for Independent Research, Medical Sciences, Johan Boserup, and the Lise Boserup’s Fund. The authors reported no conflicts of interest.

SOURCE: Benn M et al. JACC. 2019 Jun 17. doi: 10.1016/j.jacc.2019.03.517

Long-term genetically low levels of LDL cholesterol, by means of functional variants in the PCSK9 gene, were associated with a reduced risk of CV mortality, but not all-cause mortality, in a large cohort of individuals.

ktsimage/Thinkstock

“We tested the hypothesis that genetically low LDL cholesterol due to PCSK9 [proprotein convertase subtilisin/kexin type 9] variation is causally associated with low cardiovascular and all-cause mortality in a general population of Northern European ancestry,” wrote Marianne Benn, MD, DMSc, and colleagues. The findings were published in the Journal of the American College of Cardiology.

The researchers conducted a large-scale genetic analysis of 109,566 persons from the Copenhagen City Heart Study and Copenhagen General Population Study. In addition, the team included a validation cohort of 431,043 individuals from the UK Biobank.

The median duration of follow-up was 10 years (0-42 years), and the median age at study entry was 57 years.

Study participants were genotyped for several PCSK9 variants and a weighted allele score based the effects of LDL cholesterol, individual allele frequency, and number of variant alleles was calculated for each subject.

Weighted scores were categorized into five stepwise noncontinuous score ranges, with lower levels of LDL cholesterol linked to higher allele scores.

After analysis, the researchers found that a growing number of PCSK9 alleles were associated with lower levels of LDL cholesterol up to 0.61 mmol/L (P for trend less than .001) and reduced CV mortality (P = .001), but not with reduced all-cause mortality (P = .11).

“Our genetic data did not show a reduction in risk of all-cause mortality, and only showed a reduction in risk of all-cause mortality in statin trials and not in the PCSK9-inhibitor trials meta-analyzed,” the researchers wrote. “This may be explained by the low frequency of cardiovascular disease in the 2 populations studied,” they explained.

One key limitation was the homogeneous makeup of the study population. Dr. Benn and colleagues acknowledged this could limit the generalizability of the results.

“Long-term LDL cholesterol treatment (e.g., with PCSK9 inhibitors), may translate into reductions in cardiovascular mortality,” they concluded.

The study was supported by the Danish Council for Independent Research, Medical Sciences, Johan Boserup, and the Lise Boserup’s Fund. The authors reported no conflicts of interest.

SOURCE: Benn M et al. JACC. 2019 Jun 17. doi: 10.1016/j.jacc.2019.03.517

Only a limited number of patients with von Willebrand disease (VWD) are likely to require treatment with von Willebrand factor (VWF) concentrates, according to results from a retrospective analysis.

The retrospective, single-center study sought to describe the need for VWF concentrates in a “real-life setting,” wrote Ana Boban, MD, PhD, of the University of Zagreb (Croatia) and colleagues in a letter to the editor published in Haemophilia. The study was conducted at the Saint‐Luc University Hospital in Brussels and included all the VWD patients listed in the hospital registry from 2000 to 2015.

The researchers evaluated the necessity for VWF concentrate therapy based on VWD severity (mild, moderate, severe) and type (1, 2A, 2B, 2M, 2N, or 3), in addition to therapeutic indication. Bleeding scores were not included in the analysis.

A total of 174 patients with VWD were included in the study, which consisted of 116 females and 61 males aged 3-81 years. The majority of study participants had type 1 VWD (n = 118, 67%).

Data collected included patient demographic information, disease type and severity, responses to specific tests, and type of treatment received.

The researchers found that just 18% (n = 32) of patients within the cohort required therapy with VWF concentrates over the study period. Additionally, the team reported that a large number of patients did not require any therapy (n = 79; 45%) or were or managed with DDAVP (desmopressin) (n = 61; 64%).

“When assessing the results according to disease severity, it clearly occurred that most patients with severe disease required VWF concentrates [100%, 75%, and 100% for type 1, type 2, and type 3 VWD, respectively],” the authors wrote.

With respect to therapeutic indication, apart from prophylaxis, contraindications to DDAVP (n = 5) and unresponsiveness to DDAVP (n = 7) were absolute indications for the use of VWF concentrates among patients within the cohort.

“Our study has confirmed that the absolute indications for using VWF concentrates in VWD patients are prophylaxis, major surgeries, and nonresponsiveness/contraindications to DDAVP,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Boban A et al. Haemophilia. 2019 May 20. doi: 10.1111/hae.13779.

Only a limited number of patients with von Willebrand disease (VWD) are likely to require treatment with von Willebrand factor (VWF) concentrates, according to results from a retrospective analysis.

The retrospective, single-center study sought to describe the need for VWF concentrates in a “real-life setting,” wrote Ana Boban, MD, PhD, of the University of Zagreb (Croatia) and colleagues in a letter to the editor published in Haemophilia. The study was conducted at the Saint‐Luc University Hospital in Brussels and included all the VWD patients listed in the hospital registry from 2000 to 2015.

The researchers evaluated the necessity for VWF concentrate therapy based on VWD severity (mild, moderate, severe) and type (1, 2A, 2B, 2M, 2N, or 3), in addition to therapeutic indication. Bleeding scores were not included in the analysis.

A total of 174 patients with VWD were included in the study, which consisted of 116 females and 61 males aged 3-81 years. The majority of study participants had type 1 VWD (n = 118, 67%).

Data collected included patient demographic information, disease type and severity, responses to specific tests, and type of treatment received.

The researchers found that just 18% (n = 32) of patients within the cohort required therapy with VWF concentrates over the study period. Additionally, the team reported that a large number of patients did not require any therapy (n = 79; 45%) or were or managed with DDAVP (desmopressin) (n = 61; 64%).

“When assessing the results according to disease severity, it clearly occurred that most patients with severe disease required VWF concentrates [100%, 75%, and 100% for type 1, type 2, and type 3 VWD, respectively],” the authors wrote.

With respect to therapeutic indication, apart from prophylaxis, contraindications to DDAVP (n = 5) and unresponsiveness to DDAVP (n = 7) were absolute indications for the use of VWF concentrates among patients within the cohort.

“Our study has confirmed that the absolute indications for using VWF concentrates in VWD patients are prophylaxis, major surgeries, and nonresponsiveness/contraindications to DDAVP,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Boban A et al. Haemophilia. 2019 May 20. doi: 10.1111/hae.13779.

Only a limited number of patients with von Willebrand disease (VWD) are likely to require treatment with von Willebrand factor (VWF) concentrates, according to results from a retrospective analysis.

The retrospective, single-center study sought to describe the need for VWF concentrates in a “real-life setting,” wrote Ana Boban, MD, PhD, of the University of Zagreb (Croatia) and colleagues in a letter to the editor published in Haemophilia. The study was conducted at the Saint‐Luc University Hospital in Brussels and included all the VWD patients listed in the hospital registry from 2000 to 2015.

The researchers evaluated the necessity for VWF concentrate therapy based on VWD severity (mild, moderate, severe) and type (1, 2A, 2B, 2M, 2N, or 3), in addition to therapeutic indication. Bleeding scores were not included in the analysis.

A total of 174 patients with VWD were included in the study, which consisted of 116 females and 61 males aged 3-81 years. The majority of study participants had type 1 VWD (n = 118, 67%).

Data collected included patient demographic information, disease type and severity, responses to specific tests, and type of treatment received.

The researchers found that just 18% (n = 32) of patients within the cohort required therapy with VWF concentrates over the study period. Additionally, the team reported that a large number of patients did not require any therapy (n = 79; 45%) or were or managed with DDAVP (desmopressin) (n = 61; 64%).

“When assessing the results according to disease severity, it clearly occurred that most patients with severe disease required VWF concentrates [100%, 75%, and 100% for type 1, type 2, and type 3 VWD, respectively],” the authors wrote.

With respect to therapeutic indication, apart from prophylaxis, contraindications to DDAVP (n = 5) and unresponsiveness to DDAVP (n = 7) were absolute indications for the use of VWF concentrates among patients within the cohort.

“Our study has confirmed that the absolute indications for using VWF concentrates in VWD patients are prophylaxis, major surgeries, and nonresponsiveness/contraindications to DDAVP,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Boban A et al. Haemophilia. 2019 May 20. doi: 10.1111/hae.13779.

Undergoing hepatectomy for the treatment of hepatocellular carcinoma in patients with von Willebrand disease or hemophilia A was found to be safe through the use of appropriate von Willebrand factor concentrate or recombinant factor VIII therapy, according to findings from a small study.

“The aim of the present study was to evaluate the safety of hepatectomy in patients with inherited blood coagulation disorders through appropriate coagulation factor replacement,” wrote Kosuke Kobayashi, MD, PhD, of the University of Tokyo and colleagues. The findings were published in Haemophilia.

The researchers retrospectively studied seven patients with hemophilia A and three patients with von Willebrand disease who underwent hepatectomy for the treatment of hepatocellular carcinoma. Specific regimens of von Willebrand factor concentrate or recombinant factor VIII therapy were administered perioperatively in these patients.

Study participants were matched in a 2:1 ratio to 20 patients without a bleeding disorder who also underwent hepatectomy. Various intraoperative and postoperative outcomes were compared between the two groups.

The researchers found no significant differences in estimated blood loss (P = .748), operative time (P = .359), or red blood cell transfusion rate (P = .605) between the bleeding disorder and nonbleeding disorder groups.

Additionally, there were no significant differences seen for mortality rate (P greater than .999) or major complication rate (P = .605).

“Even repeated hepatectomy can be safely performed in these patients, similar to patients without coagulation disorders,” the authors wrote.

Dr. Kobayashi and colleagues acknowledged two key limitations of the study were the small sample size and retrospective design.

“The administration protocol reported in the present study would certainly help surgeons when planning hepatectomy in patients with coagulation disorders,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Kobayashi K et al. Haemophilia. 2019 May 29. doi: 10.1111/hae.13759.

Undergoing hepatectomy for the treatment of hepatocellular carcinoma in patients with von Willebrand disease or hemophilia A was found to be safe through the use of appropriate von Willebrand factor concentrate or recombinant factor VIII therapy, according to findings from a small study.

“The aim of the present study was to evaluate the safety of hepatectomy in patients with inherited blood coagulation disorders through appropriate coagulation factor replacement,” wrote Kosuke Kobayashi, MD, PhD, of the University of Tokyo and colleagues. The findings were published in Haemophilia.

The researchers retrospectively studied seven patients with hemophilia A and three patients with von Willebrand disease who underwent hepatectomy for the treatment of hepatocellular carcinoma. Specific regimens of von Willebrand factor concentrate or recombinant factor VIII therapy were administered perioperatively in these patients.

Study participants were matched in a 2:1 ratio to 20 patients without a bleeding disorder who also underwent hepatectomy. Various intraoperative and postoperative outcomes were compared between the two groups.

The researchers found no significant differences in estimated blood loss (P = .748), operative time (P = .359), or red blood cell transfusion rate (P = .605) between the bleeding disorder and nonbleeding disorder groups.

Additionally, there were no significant differences seen for mortality rate (P greater than .999) or major complication rate (P = .605).

“Even repeated hepatectomy can be safely performed in these patients, similar to patients without coagulation disorders,” the authors wrote.

Dr. Kobayashi and colleagues acknowledged two key limitations of the study were the small sample size and retrospective design.

“The administration protocol reported in the present study would certainly help surgeons when planning hepatectomy in patients with coagulation disorders,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Kobayashi K et al. Haemophilia. 2019 May 29. doi: 10.1111/hae.13759.

Undergoing hepatectomy for the treatment of hepatocellular carcinoma in patients with von Willebrand disease or hemophilia A was found to be safe through the use of appropriate von Willebrand factor concentrate or recombinant factor VIII therapy, according to findings from a small study.

“The aim of the present study was to evaluate the safety of hepatectomy in patients with inherited blood coagulation disorders through appropriate coagulation factor replacement,” wrote Kosuke Kobayashi, MD, PhD, of the University of Tokyo and colleagues. The findings were published in Haemophilia.

The researchers retrospectively studied seven patients with hemophilia A and three patients with von Willebrand disease who underwent hepatectomy for the treatment of hepatocellular carcinoma. Specific regimens of von Willebrand factor concentrate or recombinant factor VIII therapy were administered perioperatively in these patients.

Study participants were matched in a 2:1 ratio to 20 patients without a bleeding disorder who also underwent hepatectomy. Various intraoperative and postoperative outcomes were compared between the two groups.

The researchers found no significant differences in estimated blood loss (P = .748), operative time (P = .359), or red blood cell transfusion rate (P = .605) between the bleeding disorder and nonbleeding disorder groups.

Additionally, there were no significant differences seen for mortality rate (P greater than .999) or major complication rate (P = .605).

“Even repeated hepatectomy can be safely performed in these patients, similar to patients without coagulation disorders,” the authors wrote.

Dr. Kobayashi and colleagues acknowledged two key limitations of the study were the small sample size and retrospective design.

“The administration protocol reported in the present study would certainly help surgeons when planning hepatectomy in patients with coagulation disorders,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Kobayashi K et al. Haemophilia. 2019 May 29. doi: 10.1111/hae.13759.

Results from a prospective study appear to confirm the utility of the Haemophilia Early Arthropathy Detection by UltraSound (HEAD‐US) scoring system to evaluate joint bleeding rates in patients with hemophilia A who are treated exclusively with secondary or tertiary prophylaxis.

HEAD-US showed a strong correlation with the joint bleeding rate over a 3 year period for ankles and knees, but not for elbows.

“Primary prophylaxis is considered the most effective regimen in preventing arthropathy formation. However, due to social and economic reasons, a considerable number of children and young adults with haemophilia worldwide are currently treated by secondary or tertiary prophylaxis,” Atanas Banchev, MD, of University Hospital Tsaritsa Giovanna – ISUL, Bulgaria, and colleagues, wrote in a letter to the editor in Haemophilia. “Due to its wide availability and low cost, the sonographic score Haemophilia Early Arthropathy Detection by UltraSound (HEAD‐US) has recently become an attractive tool for assessment of joint status.”

The researchers conducted a prospective study of 42 patients with moderate to severe hemophilia A. The patients were treated with secondary or tertiary prophylaxis for a minimum of 5 years and had no history of inhibitors or factor VIII inhibitor antibodies.

The team collected data on patient demographics, disease characteristics, and prophylactic therapy. Patients were assessed at regular intervals at various treatment facilities throughout Bulgaria.

The scoring was based on three markers: synovitis (score 0‐2), cartilage (score 0‐4) and subchondral bone (score of 0‐2) with a maximum score of eight points per joint, according to the researchers.

A total of 250 joints were evaluated via the HEAD‐US scoring system. Dr. Banchev and colleagues reported that articular damage was present in 34% (n = 85) of joints evaluated with the tool. No defects were detected in the remaining joints (n = 165).

Mean HEAD‐US scores for each specific joint were 2.2 (range 0‐8) for ankles, 0.96 (range 0‐8) for knees, and 0.73 (range 0‐6) for elbows.

The researchers reported a strong correlation between the assessed joint bleeding rates for 3 years and the corresponding HEAD-US scores in ankles and knees. For ankles, the Spearman’s correlation coefficient was 0.545 (P less than .001) and for knees it was 0.692 (P less than .001).

They found no statistically significant correlation between the HEAD-US score and the assessed joint bleeding rates for 3 years in elbows (coefficient 0.161, P = .143).

One key limitation of the study was the nonconsideration of therapeutic compliance in the outcome assessment.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Banchev A et al. Haemophilia. 2019 May 27. doi: 10.1111/hae.13771.

Results from a prospective study appear to confirm the utility of the Haemophilia Early Arthropathy Detection by UltraSound (HEAD‐US) scoring system to evaluate joint bleeding rates in patients with hemophilia A who are treated exclusively with secondary or tertiary prophylaxis.

HEAD-US showed a strong correlation with the joint bleeding rate over a 3 year period for ankles and knees, but not for elbows.

“Primary prophylaxis is considered the most effective regimen in preventing arthropathy formation. However, due to social and economic reasons, a considerable number of children and young adults with haemophilia worldwide are currently treated by secondary or tertiary prophylaxis,” Atanas Banchev, MD, of University Hospital Tsaritsa Giovanna – ISUL, Bulgaria, and colleagues, wrote in a letter to the editor in Haemophilia. “Due to its wide availability and low cost, the sonographic score Haemophilia Early Arthropathy Detection by UltraSound (HEAD‐US) has recently become an attractive tool for assessment of joint status.”

The researchers conducted a prospective study of 42 patients with moderate to severe hemophilia A. The patients were treated with secondary or tertiary prophylaxis for a minimum of 5 years and had no history of inhibitors or factor VIII inhibitor antibodies.

The team collected data on patient demographics, disease characteristics, and prophylactic therapy. Patients were assessed at regular intervals at various treatment facilities throughout Bulgaria.

The scoring was based on three markers: synovitis (score 0‐2), cartilage (score 0‐4) and subchondral bone (score of 0‐2) with a maximum score of eight points per joint, according to the researchers.

A total of 250 joints were evaluated via the HEAD‐US scoring system. Dr. Banchev and colleagues reported that articular damage was present in 34% (n = 85) of joints evaluated with the tool. No defects were detected in the remaining joints (n = 165).

Mean HEAD‐US scores for each specific joint were 2.2 (range 0‐8) for ankles, 0.96 (range 0‐8) for knees, and 0.73 (range 0‐6) for elbows.

The researchers reported a strong correlation between the assessed joint bleeding rates for 3 years and the corresponding HEAD-US scores in ankles and knees. For ankles, the Spearman’s correlation coefficient was 0.545 (P less than .001) and for knees it was 0.692 (P less than .001).

They found no statistically significant correlation between the HEAD-US score and the assessed joint bleeding rates for 3 years in elbows (coefficient 0.161, P = .143).

One key limitation of the study was the nonconsideration of therapeutic compliance in the outcome assessment.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Banchev A et al. Haemophilia. 2019 May 27. doi: 10.1111/hae.13771.

Results from a prospective study appear to confirm the utility of the Haemophilia Early Arthropathy Detection by UltraSound (HEAD‐US) scoring system to evaluate joint bleeding rates in patients with hemophilia A who are treated exclusively with secondary or tertiary prophylaxis.

HEAD-US showed a strong correlation with the joint bleeding rate over a 3 year period for ankles and knees, but not for elbows.

“Primary prophylaxis is considered the most effective regimen in preventing arthropathy formation. However, due to social and economic reasons, a considerable number of children and young adults with haemophilia worldwide are currently treated by secondary or tertiary prophylaxis,” Atanas Banchev, MD, of University Hospital Tsaritsa Giovanna – ISUL, Bulgaria, and colleagues, wrote in a letter to the editor in Haemophilia. “Due to its wide availability and low cost, the sonographic score Haemophilia Early Arthropathy Detection by UltraSound (HEAD‐US) has recently become an attractive tool for assessment of joint status.”

The researchers conducted a prospective study of 42 patients with moderate to severe hemophilia A. The patients were treated with secondary or tertiary prophylaxis for a minimum of 5 years and had no history of inhibitors or factor VIII inhibitor antibodies.

The team collected data on patient demographics, disease characteristics, and prophylactic therapy. Patients were assessed at regular intervals at various treatment facilities throughout Bulgaria.

The scoring was based on three markers: synovitis (score 0‐2), cartilage (score 0‐4) and subchondral bone (score of 0‐2) with a maximum score of eight points per joint, according to the researchers.

A total of 250 joints were evaluated via the HEAD‐US scoring system. Dr. Banchev and colleagues reported that articular damage was present in 34% (n = 85) of joints evaluated with the tool. No defects were detected in the remaining joints (n = 165).

Mean HEAD‐US scores for each specific joint were 2.2 (range 0‐8) for ankles, 0.96 (range 0‐8) for knees, and 0.73 (range 0‐6) for elbows.

The researchers reported a strong correlation between the assessed joint bleeding rates for 3 years and the corresponding HEAD-US scores in ankles and knees. For ankles, the Spearman’s correlation coefficient was 0.545 (P less than .001) and for knees it was 0.692 (P less than .001).

They found no statistically significant correlation between the HEAD-US score and the assessed joint bleeding rates for 3 years in elbows (coefficient 0.161, P = .143).

One key limitation of the study was the nonconsideration of therapeutic compliance in the outcome assessment.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Banchev A et al. Haemophilia. 2019 May 27. doi: 10.1111/hae.13771.

Combined aerobic and resistance exercise training was found to be the most effective training technique to reduce proinflammatory markers in overweight patients with moderate hemophilia A.

“Combined training has been established as the most effective type of exercise in terms of modification of cardiovascular disease risk factors,” wrote Behrouz Parhampour, of Iran University of Medical Sciences in Tehran, and colleagues. The findings of the study were published in Haemophilia.

The researchers conducted a randomized clinical study of 48 patients with moderate hemophilia A. Study patients had a body mass index of 25-30 kg/m² and were aged 35-55 years.

Study participants were randomly allocated to aerobic training (n = 12), resistance training (n = 12), combined training (n = 12), and control (n = 12) arms. The training regimens consisted of 45‐minute sessions three times per week for a total of 6 weeks.

Interleukin‐10, adiponectin, tumor necrosis factor–alpha, IL‐6, and high-sensitive C‐reactive protein were measured before and after training. Weight-related measures, including waist‐to‐hip ratio and waist circumference, were also evaluated.

The researchers found there was a significant reduction in weight, waist‐to‐hip ratio, waist circumference, and body mass index in the combined, resistance, and aerobic training arms, compared with the control arm.

Additionally, they reported a significant reduction in high-sensitive C‐reactive protein, IL‐6, and tumor necrosis factor–alpha levels in the combined training group versus the control group (P equal to or less than .02 for all three).

There were no episodes of bleeding among patients in any of the intervention groups.

“The possible mechanism for the effect of exercise training on weight loss is to increase metabolic consumption which may subsequently reduce the low‐grade inflammation commonly noted among overweight patients,” the researchers wrote.

The authors acknowledged that two key limitations of the study were the short duration of training and small sample size.

“Combined training can be used as an effective nonpharmacological strategy to improve joint function and prevent disorders associated with sedentary lifestyle like cardiovascular complications in [hemophilia patients],” they concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Parhampour B et al. Haemophilia. 2019 May 26. doi: 10.1111/hae.13764.

Combined aerobic and resistance exercise training was found to be the most effective training technique to reduce proinflammatory markers in overweight patients with moderate hemophilia A.

“Combined training has been established as the most effective type of exercise in terms of modification of cardiovascular disease risk factors,” wrote Behrouz Parhampour, of Iran University of Medical Sciences in Tehran, and colleagues. The findings of the study were published in Haemophilia.

The researchers conducted a randomized clinical study of 48 patients with moderate hemophilia A. Study patients had a body mass index of 25-30 kg/m² and were aged 35-55 years.

Study participants were randomly allocated to aerobic training (n = 12), resistance training (n = 12), combined training (n = 12), and control (n = 12) arms. The training regimens consisted of 45‐minute sessions three times per week for a total of 6 weeks.

Interleukin‐10, adiponectin, tumor necrosis factor–alpha, IL‐6, and high-sensitive C‐reactive protein were measured before and after training. Weight-related measures, including waist‐to‐hip ratio and waist circumference, were also evaluated.

The researchers found there was a significant reduction in weight, waist‐to‐hip ratio, waist circumference, and body mass index in the combined, resistance, and aerobic training arms, compared with the control arm.

Additionally, they reported a significant reduction in high-sensitive C‐reactive protein, IL‐6, and tumor necrosis factor–alpha levels in the combined training group versus the control group (P equal to or less than .02 for all three).

There were no episodes of bleeding among patients in any of the intervention groups.

“The possible mechanism for the effect of exercise training on weight loss is to increase metabolic consumption which may subsequently reduce the low‐grade inflammation commonly noted among overweight patients,” the researchers wrote.

The authors acknowledged that two key limitations of the study were the short duration of training and small sample size.

“Combined training can be used as an effective nonpharmacological strategy to improve joint function and prevent disorders associated with sedentary lifestyle like cardiovascular complications in [hemophilia patients],” they concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Parhampour B et al. Haemophilia. 2019 May 26. doi: 10.1111/hae.13764.

Combined aerobic and resistance exercise training was found to be the most effective training technique to reduce proinflammatory markers in overweight patients with moderate hemophilia A.

“Combined training has been established as the most effective type of exercise in terms of modification of cardiovascular disease risk factors,” wrote Behrouz Parhampour, of Iran University of Medical Sciences in Tehran, and colleagues. The findings of the study were published in Haemophilia.

The researchers conducted a randomized clinical study of 48 patients with moderate hemophilia A. Study patients had a body mass index of 25-30 kg/m² and were aged 35-55 years.

Study participants were randomly allocated to aerobic training (n = 12), resistance training (n = 12), combined training (n = 12), and control (n = 12) arms. The training regimens consisted of 45‐minute sessions three times per week for a total of 6 weeks.

Interleukin‐10, adiponectin, tumor necrosis factor–alpha, IL‐6, and high-sensitive C‐reactive protein were measured before and after training. Weight-related measures, including waist‐to‐hip ratio and waist circumference, were also evaluated.

The researchers found there was a significant reduction in weight, waist‐to‐hip ratio, waist circumference, and body mass index in the combined, resistance, and aerobic training arms, compared with the control arm.

Additionally, they reported a significant reduction in high-sensitive C‐reactive protein, IL‐6, and tumor necrosis factor–alpha levels in the combined training group versus the control group (P equal to or less than .02 for all three).

There were no episodes of bleeding among patients in any of the intervention groups.

“The possible mechanism for the effect of exercise training on weight loss is to increase metabolic consumption which may subsequently reduce the low‐grade inflammation commonly noted among overweight patients,” the researchers wrote.

The authors acknowledged that two key limitations of the study were the short duration of training and small sample size.

“Combined training can be used as an effective nonpharmacological strategy to improve joint function and prevent disorders associated with sedentary lifestyle like cardiovascular complications in [hemophilia patients],” they concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Parhampour B et al. Haemophilia. 2019 May 26. doi: 10.1111/hae.13764.

Red blood cell (RBC) transfusions from either previously pregnant, sex-discordant, or female donors were not significantly associated with higher mortality among transfusion recipients, according to a retrospective analysis of more than 1 million donors.

“This study used data from 3 large cohorts in the United States and Scandinavia to investigate whether blood donor sex and pregnancy history were associated with mortality of transfusion recipients,” wrote Gustaf Edgren, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues. The findings were published in JAMA.

The researchers analyzed data from three separate cohorts that included a combined 1,047,382 red blood cell transfusion recipients. Data collected included donor-related information, such as sex and pregnancy history, as well as survival data of transfusion recipients. The primary outcome measured was in-hospital mortality, and the secondary outcome was long-term mortality. Data were collected until Dec. 31, 2016.

The researchers found no statistically significant associations between either sex-discordant donors (male donor to female recipient or female donor to male recipient), female donors, or previously pregnant donors and in-hospital mortality of transfusion recipients.

The hazard ratio estimates for each unit transfused from a previously pregnant donor ranged from 1.00-1.01 in the three cohorts. Similarly, the HR estimates ranged from 0.99-1.00 for female donors in the three cohorts and 0.99-1.02 for sex discordant donors.

The only significant association found was observed in the smallest cohort of 34,662 recipients. Researchers found an increased risk of death in patients who received one to two sex discordant transfusions (HR, 1.08; 95% confidence interval, 1.03-1.14) or five to six transfusions (HR, 1.14; 95%CI, 1.01-1.29), compared with recipients who received no sex-discordant transfusions.

“The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know,” Simone Glynn, MD, chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute, as well as a study author, said in a statement.

The study was funded by the National Heart, Lung, and Blood Institute. The authors reported financial disclosures related to the National Institutes of Health, RTI International, Cerus, AABB, Creative Testing Solutions, and the Nordic Cancer Union.

SOURCE: Edgren G et al. JAMA. 2019 Jun 11. doi: 10.1001/jama.2019.7084.

Red blood cell (RBC) transfusions from either previously pregnant, sex-discordant, or female donors were not significantly associated with higher mortality among transfusion recipients, according to a retrospective analysis of more than 1 million donors.

“This study used data from 3 large cohorts in the United States and Scandinavia to investigate whether blood donor sex and pregnancy history were associated with mortality of transfusion recipients,” wrote Gustaf Edgren, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues. The findings were published in JAMA.

The researchers analyzed data from three separate cohorts that included a combined 1,047,382 red blood cell transfusion recipients. Data collected included donor-related information, such as sex and pregnancy history, as well as survival data of transfusion recipients. The primary outcome measured was in-hospital mortality, and the secondary outcome was long-term mortality. Data were collected until Dec. 31, 2016.

The researchers found no statistically significant associations between either sex-discordant donors (male donor to female recipient or female donor to male recipient), female donors, or previously pregnant donors and in-hospital mortality of transfusion recipients.

The hazard ratio estimates for each unit transfused from a previously pregnant donor ranged from 1.00-1.01 in the three cohorts. Similarly, the HR estimates ranged from 0.99-1.00 for female donors in the three cohorts and 0.99-1.02 for sex discordant donors.

The only significant association found was observed in the smallest cohort of 34,662 recipients. Researchers found an increased risk of death in patients who received one to two sex discordant transfusions (HR, 1.08; 95% confidence interval, 1.03-1.14) or five to six transfusions (HR, 1.14; 95%CI, 1.01-1.29), compared with recipients who received no sex-discordant transfusions.

“The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know,” Simone Glynn, MD, chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute, as well as a study author, said in a statement.

The study was funded by the National Heart, Lung, and Blood Institute. The authors reported financial disclosures related to the National Institutes of Health, RTI International, Cerus, AABB, Creative Testing Solutions, and the Nordic Cancer Union.

SOURCE: Edgren G et al. JAMA. 2019 Jun 11. doi: 10.1001/jama.2019.7084.

Red blood cell (RBC) transfusions from either previously pregnant, sex-discordant, or female donors were not significantly associated with higher mortality among transfusion recipients, according to a retrospective analysis of more than 1 million donors.

“This study used data from 3 large cohorts in the United States and Scandinavia to investigate whether blood donor sex and pregnancy history were associated with mortality of transfusion recipients,” wrote Gustaf Edgren, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues. The findings were published in JAMA.

The researchers analyzed data from three separate cohorts that included a combined 1,047,382 red blood cell transfusion recipients. Data collected included donor-related information, such as sex and pregnancy history, as well as survival data of transfusion recipients. The primary outcome measured was in-hospital mortality, and the secondary outcome was long-term mortality. Data were collected until Dec. 31, 2016.

The researchers found no statistically significant associations between either sex-discordant donors (male donor to female recipient or female donor to male recipient), female donors, or previously pregnant donors and in-hospital mortality of transfusion recipients.

The hazard ratio estimates for each unit transfused from a previously pregnant donor ranged from 1.00-1.01 in the three cohorts. Similarly, the HR estimates ranged from 0.99-1.00 for female donors in the three cohorts and 0.99-1.02 for sex discordant donors.

The only significant association found was observed in the smallest cohort of 34,662 recipients. Researchers found an increased risk of death in patients who received one to two sex discordant transfusions (HR, 1.08; 95% confidence interval, 1.03-1.14) or five to six transfusions (HR, 1.14; 95%CI, 1.01-1.29), compared with recipients who received no sex-discordant transfusions.

“The results are reassuring in that the survival of patients who got transfused with red blood cells does not appear to be associated with whether the blood they received was donated by a man, by a woman who had been pregnant — or by one who had not. That’s important to know,” Simone Glynn, MD, chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute, as well as a study author, said in a statement.

The study was funded by the National Heart, Lung, and Blood Institute. The authors reported financial disclosures related to the National Institutes of Health, RTI International, Cerus, AABB, Creative Testing Solutions, and the Nordic Cancer Union.

SOURCE: Edgren G et al. JAMA. 2019 Jun 11. doi: 10.1001/jama.2019.7084.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

In women with hormone receptor–positive, axillary node–negative breast cancer with Oncotype DX recurrence scores of less than 26, there is minimal to no benefit from chemotherapy, particularly for those greater than age 50 years, according to a clinical practice guideline update by the American Society of Clinical Oncology.

Furthermore, endocrine therapy alone may be offered for patients greater than age 50 years whose tumors have recurrence scores of less than 26, wrote Fabrice Andre, MD, PhD, of Paris Sud University and associates on the expert panel in the Journal of Clinical Oncology.

The panel members reviewed recently published findings from the Trial Assigning Individualized Options for Treatment (TAILORx), which evaluated the clinical utility of the Oncotype DX assay in women with early-stage invasive breast cancer.

“This focused update reviews and analyzes new data regarding these recommendations while applying the same criteria of clinical utility as described in the 2016 guideline,” they wrote.

The expert panel provided recommendations on how to integrate the results of the TAILORx study into clinical practice.

“For patients age 50 years or younger with Oncotype DX recurrence scores of 16-25, clinicians may offer chemoendocrine therapy” the panel wrote. “Patients with Oncotype DX recurrence scores of greater than 30 should be considered candidates for chemoendocrine therapy.”

In addition, on the basis of consensus they recommended that chemoendocrine therapy could be offered to patients with recurrence scores of 26-30.

The panel acknowledged that relevant literature on the use of Oncotype DX in this population will be reviewed over the upcoming months to address anticipated practice deviation related to biomarker testing.

More information on the guidelines is available on the ASCO website.

The study was funded by ASCO. The authors reported financial affiliations with AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Roche, and several others.

SOURCE: Andre F et al. J Clin Oncol. 2019 May 31. doi: 10.1200/JCO.19.00945.

The National Comprehensive Cancer Network (NCCN) has issued new clinical practice guidelines for the treatment of pediatric acute lymphoblastic leukemia (ALL).

“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.

“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.

The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.

The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).

While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.

The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.

“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.

Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.

The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.

Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.

Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.

“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
 

The National Comprehensive Cancer Network (NCCN) has issued new clinical practice guidelines for the treatment of pediatric acute lymphoblastic leukemia (ALL).

“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.

“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.

The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.

The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).

While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.

The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.

“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.

Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.

The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.

Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.

Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.

“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
 

The National Comprehensive Cancer Network (NCCN) has issued new clinical practice guidelines for the treatment of pediatric acute lymphoblastic leukemia (ALL).

“The cure rate for pediatric ALL in the U.S. has risen from 0% in the 1960s to nearly 90% today. This is among the most profound medical success stories in history,” Patrick Brown, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said in a statement announcing the guidelines. Dr. Brown chairs the NCCN Clinical Practice Guidelines for adult and pediatric ALL.

“Pediatric ALL survivors live a long time; we have to consider long-term effects as well,” Hiroto Inaba, MD, PhD, of St. Jude Children’s Research Hospital, Memphis, and vice chair of the guidelines committee, said in the statement.

The new recommendations highlight the importance of supportive care interventions in an effort to reduce the chances of patients experiencing severe adverse effects.

The pediatric ALL guidelines provide evidence-based recommendations about optimal treatment strategies for ALL to prolong survival in children affected, with a focus on treatment outside of clinical trials (Pediatric Acute Lymphoblastic Leukemia. NCCN.org, Version 1.2019, published May 30, 2019).

While treatment for ALL often includes long-term chemotherapy regimens that involve multiple stages, several novel treatment strategies are summarized in the guidelines, including various types of immunotherapy and targeted therapy.

The guidelines are intended to accompany the NCCN Guidelines for Adult ALL and integrate treatment recommendations for patients in overlapping age categories. The recommendations are organized based on risk level, which may also be associated with age.

“The highest risk [is] associated with those diagnosed within the first 12 months of life or between the ages 10 and 21 years old,” the guideline authors wrote.

Another unique aspect of the guidelines is the recognition of vulnerable populations, such as young infants or children with Down syndrome, who face distinct treatment challenges. The authors provide guidance on the best supportive care measures for these patients.

The NCCN is currently expanding the collection of clinical practice guidelines for additional pediatric malignancies. At present, they are planning to undertake a minimum of 90% of all incident pediatric cancers.

Upcoming guidelines include treatment recommendations for pediatric Burkitt lymphoma, and are scheduled for release later in 2019.

Future efforts include modifying the guidelines for use in low- and middle-income countries, with the goal of providing direction in resource-limited environments.

“We know that many, many children can be cured with inexpensive and widely-available therapies,” Dr. Brown said. “With the increasing global reach of the NCCN Guidelines, we can really pave the way for increasing the cure rates throughout the world.”
 

Cediranib was found to confer sensitivity to olaparib through downregulation of the homology-directed DNA repair (HDR) pathway in tumor cells, investigators report.

“The objective of this study was to define the effects of cediranib on the HDR pathway of DNA repair,” wrote Alanna R. Kaplan, MD, of Yale University, New Haven, Conn., and colleagues. The report is in Science Translational Medicine.

The researchers explored the effects of combination cediranib and olaparib therapy at the molecular level using various in vitro and in vivo experiments. Tumor growth studies were conducted in a mouse model with sample sizes selected based on prior experience.

“In vitro experiments were performed in biological triplicate unless otherwise stated,” the researchers wrote. “For in vivo experiments, mice were randomly assigned to treatment groups,” they added.

After analysis, the researchers found that cediranib provides sensitivity to olaparib through suppression of the HDR pathway in malignant cells. The downregulation was explained in part by the inducement of hypoxia, which inhibited gene expression of certain factors in the pathway.

“We noted a decrease in the expression of HDR factors BRCA1, BRCA2, and RAD51 in the cediranib-treated groups compared to controls,” the researchers explained.

In addition, the team reported that cediranib alone exhibits direct effects on the HDR pathway outside of mechanisms related to tumor hypoxia.

“This downregulation was seen in mouse tumor xenografts but not in mouse bone marrow, providing a therapeutic window for combining cediranib and olaparib in cancer therapy,” the team wrote.

The researchers acknowledged that a key limitation of the study was the lack of inquiry into the effects of other mutations on the HDR pathway, which could possibly influence the effects of cediranib in tumor cells.

“These findings identify a pathway by which cediranib can alter the DNA repair capacity of cancer cells that has implications for the design of cancer therapies,” the authors concluded.

The study was supported by grant funding from the National Institutes of Health. One of the researchers reported financial affiliations with Trucode Gene Repair, Cybrexa Therapeutics, and Patrys.

SOURCE: Kaplan AR et al. Sci Transl Med. 2019 May 15. doi: 10.1126/scitranslmed.aav4508.

Cediranib was found to confer sensitivity to olaparib through downregulation of the homology-directed DNA repair (HDR) pathway in tumor cells, investigators report.

“The objective of this study was to define the effects of cediranib on the HDR pathway of DNA repair,” wrote Alanna R. Kaplan, MD, of Yale University, New Haven, Conn., and colleagues. The report is in Science Translational Medicine.

The researchers explored the effects of combination cediranib and olaparib therapy at the molecular level using various in vitro and in vivo experiments. Tumor growth studies were conducted in a mouse model with sample sizes selected based on prior experience.

“In vitro experiments were performed in biological triplicate unless otherwise stated,” the researchers wrote. “For in vivo experiments, mice were randomly assigned to treatment groups,” they added.

After analysis, the researchers found that cediranib provides sensitivity to olaparib through suppression of the HDR pathway in malignant cells. The downregulation was explained in part by the inducement of hypoxia, which inhibited gene expression of certain factors in the pathway.

“We noted a decrease in the expression of HDR factors BRCA1, BRCA2, and RAD51 in the cediranib-treated groups compared to controls,” the researchers explained.

In addition, the team reported that cediranib alone exhibits direct effects on the HDR pathway outside of mechanisms related to tumor hypoxia.

“This downregulation was seen in mouse tumor xenografts but not in mouse bone marrow, providing a therapeutic window for combining cediranib and olaparib in cancer therapy,” the team wrote.

The researchers acknowledged that a key limitation of the study was the lack of inquiry into the effects of other mutations on the HDR pathway, which could possibly influence the effects of cediranib in tumor cells.

“These findings identify a pathway by which cediranib can alter the DNA repair capacity of cancer cells that has implications for the design of cancer therapies,” the authors concluded.

The study was supported by grant funding from the National Institutes of Health. One of the researchers reported financial affiliations with Trucode Gene Repair, Cybrexa Therapeutics, and Patrys.

SOURCE: Kaplan AR et al. Sci Transl Med. 2019 May 15. doi: 10.1126/scitranslmed.aav4508.

Cediranib was found to confer sensitivity to olaparib through downregulation of the homology-directed DNA repair (HDR) pathway in tumor cells, investigators report.

“The objective of this study was to define the effects of cediranib on the HDR pathway of DNA repair,” wrote Alanna R. Kaplan, MD, of Yale University, New Haven, Conn., and colleagues. The report is in Science Translational Medicine.

The researchers explored the effects of combination cediranib and olaparib therapy at the molecular level using various in vitro and in vivo experiments. Tumor growth studies were conducted in a mouse model with sample sizes selected based on prior experience.

“In vitro experiments were performed in biological triplicate unless otherwise stated,” the researchers wrote. “For in vivo experiments, mice were randomly assigned to treatment groups,” they added.

After analysis, the researchers found that cediranib provides sensitivity to olaparib through suppression of the HDR pathway in malignant cells. The downregulation was explained in part by the inducement of hypoxia, which inhibited gene expression of certain factors in the pathway.

“We noted a decrease in the expression of HDR factors BRCA1, BRCA2, and RAD51 in the cediranib-treated groups compared to controls,” the researchers explained.

In addition, the team reported that cediranib alone exhibits direct effects on the HDR pathway outside of mechanisms related to tumor hypoxia.

“This downregulation was seen in mouse tumor xenografts but not in mouse bone marrow, providing a therapeutic window for combining cediranib and olaparib in cancer therapy,” the team wrote.

The researchers acknowledged that a key limitation of the study was the lack of inquiry into the effects of other mutations on the HDR pathway, which could possibly influence the effects of cediranib in tumor cells.

“These findings identify a pathway by which cediranib can alter the DNA repair capacity of cancer cells that has implications for the design of cancer therapies,” the authors concluded.

The study was supported by grant funding from the National Institutes of Health. One of the researchers reported financial affiliations with Trucode Gene Repair, Cybrexa Therapeutics, and Patrys.

SOURCE: Kaplan AR et al. Sci Transl Med. 2019 May 15. doi: 10.1126/scitranslmed.aav4508.

The novel anti–programmed cell death antibody PF-06801591 had tolerable safety and efficacy outcomes when given subcutaneously to patients with advanced solid tumors, based on results from an ongoing phase 1 trial.

“We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death [PD-1] receptor,” Melissa L. Johnson, MD, of the Sarah Cannon Research Institute, Nashville, Tenn., and colleagues wrote in JAMA Oncology. “Subcutaneous administration of an anti-PD-1 antibody in patients with advanced solid tumors appears to be feasible.”

The researchers evaluated the efficacy, safety, and pharmacokinetics of the novel anti-PD-1 therapy in a group of 40 patients with locally advanced or metastatic solid tumors. The antibody was administered in both subcutaneous and intravenous forms.

Study participants were administered the subcutaneous form of the antibody at 300 mg every 4 weeks or the intravenous form at 0.5, 1, 3, or 10 mg/kg every 3 weeks.

“Dose escalation occurred after two to four patients were enrolled per dose level, with additional patients enrolled in each cohort for further assessment,” the researchers wrote.

The primary endpoints were safety and dose-limiting adverse effects. Efficacy, immunogenicity, pharmacokinetics, and PD-1 receptor occupancy were secondary endpoints.

After analysis, Dr. Johnson and colleagues reported that the overall response rate was 18.4%. In addition, no dose-limiting toxicities were detected in both intravenous and subcutaneous groups, but grade 3 or greater adverse events were reported in 6.7% and 16% of patients treated with subcutaneous and intravenous dosage forms, respectively.

“No dose–adverse event associations were observed during intravenous dose escalation, and no serious skin toxic effects occurred with subcutaneous delivery,” they reported.

Based on the findings, the team selected the subcutaneous form (300 mg) of the therapy for additional assessment in the second half of this ongoing trial.

The study was funded by Pfizer. The authors reported financial affiliations with BerGenBio, EMD Serono, Janssen, Mirati Therapeutics, Pfizer, and several others.

SOURCE: Johnson ML et al. JAMA Oncol. 2019 May 30. doi: 10.1001/jamaoncol.2019.0836.

The novel anti–programmed cell death antibody PF-06801591 had tolerable safety and efficacy outcomes when given subcutaneously to patients with advanced solid tumors, based on results from an ongoing phase 1 trial.

“We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death [PD-1] receptor,” Melissa L. Johnson, MD, of the Sarah Cannon Research Institute, Nashville, Tenn., and colleagues wrote in JAMA Oncology. “Subcutaneous administration of an anti-PD-1 antibody in patients with advanced solid tumors appears to be feasible.”

The researchers evaluated the efficacy, safety, and pharmacokinetics of the novel anti-PD-1 therapy in a group of 40 patients with locally advanced or metastatic solid tumors. The antibody was administered in both subcutaneous and intravenous forms.

Study participants were administered the subcutaneous form of the antibody at 300 mg every 4 weeks or the intravenous form at 0.5, 1, 3, or 10 mg/kg every 3 weeks.

“Dose escalation occurred after two to four patients were enrolled per dose level, with additional patients enrolled in each cohort for further assessment,” the researchers wrote.

The primary endpoints were safety and dose-limiting adverse effects. Efficacy, immunogenicity, pharmacokinetics, and PD-1 receptor occupancy were secondary endpoints.

After analysis, Dr. Johnson and colleagues reported that the overall response rate was 18.4%. In addition, no dose-limiting toxicities were detected in both intravenous and subcutaneous groups, but grade 3 or greater adverse events were reported in 6.7% and 16% of patients treated with subcutaneous and intravenous dosage forms, respectively.

“No dose–adverse event associations were observed during intravenous dose escalation, and no serious skin toxic effects occurred with subcutaneous delivery,” they reported.

Based on the findings, the team selected the subcutaneous form (300 mg) of the therapy for additional assessment in the second half of this ongoing trial.

The study was funded by Pfizer. The authors reported financial affiliations with BerGenBio, EMD Serono, Janssen, Mirati Therapeutics, Pfizer, and several others.

SOURCE: Johnson ML et al. JAMA Oncol. 2019 May 30. doi: 10.1001/jamaoncol.2019.0836.

The novel anti–programmed cell death antibody PF-06801591 had tolerable safety and efficacy outcomes when given subcutaneously to patients with advanced solid tumors, based on results from an ongoing phase 1 trial.

“We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death [PD-1] receptor,” Melissa L. Johnson, MD, of the Sarah Cannon Research Institute, Nashville, Tenn., and colleagues wrote in JAMA Oncology. “Subcutaneous administration of an anti-PD-1 antibody in patients with advanced solid tumors appears to be feasible.”

The researchers evaluated the efficacy, safety, and pharmacokinetics of the novel anti-PD-1 therapy in a group of 40 patients with locally advanced or metastatic solid tumors. The antibody was administered in both subcutaneous and intravenous forms.

Study participants were administered the subcutaneous form of the antibody at 300 mg every 4 weeks or the intravenous form at 0.5, 1, 3, or 10 mg/kg every 3 weeks.

“Dose escalation occurred after two to four patients were enrolled per dose level, with additional patients enrolled in each cohort for further assessment,” the researchers wrote.

The primary endpoints were safety and dose-limiting adverse effects. Efficacy, immunogenicity, pharmacokinetics, and PD-1 receptor occupancy were secondary endpoints.

After analysis, Dr. Johnson and colleagues reported that the overall response rate was 18.4%. In addition, no dose-limiting toxicities were detected in both intravenous and subcutaneous groups, but grade 3 or greater adverse events were reported in 6.7% and 16% of patients treated with subcutaneous and intravenous dosage forms, respectively.

“No dose–adverse event associations were observed during intravenous dose escalation, and no serious skin toxic effects occurred with subcutaneous delivery,” they reported.

Based on the findings, the team selected the subcutaneous form (300 mg) of the therapy for additional assessment in the second half of this ongoing trial.

The study was funded by Pfizer. The authors reported financial affiliations with BerGenBio, EMD Serono, Janssen, Mirati Therapeutics, Pfizer, and several others.

SOURCE: Johnson ML et al. JAMA Oncol. 2019 May 30. doi: 10.1001/jamaoncol.2019.0836.