Hematology Times

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

US cancer centers have substantially increased spending for consumer-directed advertising in recent years, according to researchers.

The team looked at consumer advertising for 890 cancer centers and found that total advertising spending for these centers increased from $54,229,849 in 2005 to $173,510,900 in 2014.

The researchers reported these findings in a letter to JAMA Internal Medicine.

The team analyzed data from an agency that tracks the content and number of advertisements and calculates expenditures. An advertiser was considered a cancer center if its name contained certain key words.

Advertising expenditure data covered 6 media outlets: television, magazines, radio, newspapers, billboards, and the Internet.

According to these data, from 2005 to 2014, 890 cancer centers advertised to the public. In general, inflation-adjusted spending increased for all of the types of advertising the researchers analyzed.

The team said the greatest relative growth in spending was for Internet display advertisements, which increased from less than 1% of total advertising spending in 2005 ($302,030/$54,229,849) to 5% in 2014 ($8,633,000/$173,510,900).

The researchers also found that, in 2014, 20 cancer centers accounted for 86% of the roughly $174 million total advertising spending.

Cancer Treatment Centers of America spent the most (at $101.7 million), followed by MD Anderson Cancer Center (at $13.9 million) and Memorial Sloan Kettering Cancer Center (at $9.1 million).

Among the 20 centers, 5 were for-profit, 17 were Commission on Cancer-accredited, and 9 were National Cancer Institute-designated.

The researchers said their findings likely underestimate advertising spending because the available data didn’t include all types of advertising, such as ads in cancer-specific magazines.

The team also said the effect of cancer-center advertising on the quality and costs of cancer care should be investigated.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

US cancer centers have substantially increased spending for consumer-directed advertising in recent years, according to researchers.

The team looked at consumer advertising for 890 cancer centers and found that total advertising spending for these centers increased from $54,229,849 in 2005 to $173,510,900 in 2014.

The researchers reported these findings in a letter to JAMA Internal Medicine.

The team analyzed data from an agency that tracks the content and number of advertisements and calculates expenditures. An advertiser was considered a cancer center if its name contained certain key words.

Advertising expenditure data covered 6 media outlets: television, magazines, radio, newspapers, billboards, and the Internet.

According to these data, from 2005 to 2014, 890 cancer centers advertised to the public. In general, inflation-adjusted spending increased for all of the types of advertising the researchers analyzed.

The team said the greatest relative growth in spending was for Internet display advertisements, which increased from less than 1% of total advertising spending in 2005 ($302,030/$54,229,849) to 5% in 2014 ($8,633,000/$173,510,900).

The researchers also found that, in 2014, 20 cancer centers accounted for 86% of the roughly $174 million total advertising spending.

Cancer Treatment Centers of America spent the most (at $101.7 million), followed by MD Anderson Cancer Center (at $13.9 million) and Memorial Sloan Kettering Cancer Center (at $9.1 million).

Among the 20 centers, 5 were for-profit, 17 were Commission on Cancer-accredited, and 9 were National Cancer Institute-designated.

The researchers said their findings likely underestimate advertising spending because the available data didn’t include all types of advertising, such as ads in cancer-specific magazines.

The team also said the effect of cancer-center advertising on the quality and costs of cancer care should be investigated.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

US cancer centers have substantially increased spending for consumer-directed advertising in recent years, according to researchers.

The team looked at consumer advertising for 890 cancer centers and found that total advertising spending for these centers increased from $54,229,849 in 2005 to $173,510,900 in 2014.

The researchers reported these findings in a letter to JAMA Internal Medicine.

The team analyzed data from an agency that tracks the content and number of advertisements and calculates expenditures. An advertiser was considered a cancer center if its name contained certain key words.

Advertising expenditure data covered 6 media outlets: television, magazines, radio, newspapers, billboards, and the Internet.

According to these data, from 2005 to 2014, 890 cancer centers advertised to the public. In general, inflation-adjusted spending increased for all of the types of advertising the researchers analyzed.

The team said the greatest relative growth in spending was for Internet display advertisements, which increased from less than 1% of total advertising spending in 2005 ($302,030/$54,229,849) to 5% in 2014 ($8,633,000/$173,510,900).

The researchers also found that, in 2014, 20 cancer centers accounted for 86% of the roughly $174 million total advertising spending.

Cancer Treatment Centers of America spent the most (at $101.7 million), followed by MD Anderson Cancer Center (at $13.9 million) and Memorial Sloan Kettering Cancer Center (at $9.1 million).

Among the 20 centers, 5 were for-profit, 17 were Commission on Cancer-accredited, and 9 were National Cancer Institute-designated.

The researchers said their findings likely underestimate advertising spending because the available data didn’t include all types of advertising, such as ads in cancer-specific magazines.

The team also said the effect of cancer-center advertising on the quality and costs of cancer care should be investigated.

Researcher in the lab

Photo by Daniel Sone

Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).

This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.

“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.

“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”

With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.

The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).

BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.

It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.

The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.

The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.

“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.

“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”

Researcher in the lab

Photo by Daniel Sone

Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).

This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.

“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.

“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”

With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.

The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).

BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.

It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.

The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.

The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.

“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.

“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”

Researcher in the lab

Photo by Daniel Sone

Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).

This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.

“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.

“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”

With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.

The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).

BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.

It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.

The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.

The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.

“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.

“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”

Blood for transfusion
Photo by Elise Amendola

A large study has revealed an unexpected association between blood donor characteristics and transfusion recipients’ outcomes.

It is the first study to suggest that red blood cell (RBC) transfusions from younger donors or female donors may increase the risk of death in recipients.

“We need further research to confirm these findings and to look at possible biological mechanisms,” said Michaël Chassé, MD, PhD, of Université Laval in Quebec, Canada.

“One possibility is that components in the blood of younger donors or female donors may affect the immune system of the transfusion recipient.”

For this study, Dr Chassé and his colleagues linked 30,503 patients who received a transfusion at The Ottawa Hospital between October 2006 and December 2013 with their respective blood donors (80,755 donors in total).

The average age of the recipients was 66.2 years. They were followed for an average of 2.3 years, with a maximum follow-up time of 7.2 years.

The researchers found that recipients of RBCs from female donors had an 8% increased risk of death from any cause per unit transfused, when compared with recipients of RBCs from male donors. The adjusted hazard ratio (aHR) was 1.08 (95% CI, 1.06-1.09; P<0.001).

A similar increased risk of death was observed for recipients of RBCs from younger donors. When compared to recipients of RBCs from donors ages 40 to 49.9, the risk of death was higher for recipients of RBCs from donors ages 17 to 19.9 (aHR=1.08; 95% CI, 1.06-1.10; P<0.001) and recipients of RBCs from donors ages 20 to 29.9 (aHR=1.06; 95% CI, 1.04-1.09; P<0.001).

“Though our research suggests that we should investigate what’s behind the associations that we found, there is no definitive evidence yet that proves that one type of blood is better or worse for patients,” said Jason Acker, PhD, of Canadian Blood Services in Edmonton, Alberta.

“This study opens up new areas of investigation where we can really dig into the biological explanations and understand true cause and effect.”

The study was published in JAMA Internal Medicine.

Blood for transfusion
Photo by Elise Amendola

A large study has revealed an unexpected association between blood donor characteristics and transfusion recipients’ outcomes.

It is the first study to suggest that red blood cell (RBC) transfusions from younger donors or female donors may increase the risk of death in recipients.

“We need further research to confirm these findings and to look at possible biological mechanisms,” said Michaël Chassé, MD, PhD, of Université Laval in Quebec, Canada.

“One possibility is that components in the blood of younger donors or female donors may affect the immune system of the transfusion recipient.”

For this study, Dr Chassé and his colleagues linked 30,503 patients who received a transfusion at The Ottawa Hospital between October 2006 and December 2013 with their respective blood donors (80,755 donors in total).

The average age of the recipients was 66.2 years. They were followed for an average of 2.3 years, with a maximum follow-up time of 7.2 years.

The researchers found that recipients of RBCs from female donors had an 8% increased risk of death from any cause per unit transfused, when compared with recipients of RBCs from male donors. The adjusted hazard ratio (aHR) was 1.08 (95% CI, 1.06-1.09; P<0.001).

A similar increased risk of death was observed for recipients of RBCs from younger donors. When compared to recipients of RBCs from donors ages 40 to 49.9, the risk of death was higher for recipients of RBCs from donors ages 17 to 19.9 (aHR=1.08; 95% CI, 1.06-1.10; P<0.001) and recipients of RBCs from donors ages 20 to 29.9 (aHR=1.06; 95% CI, 1.04-1.09; P<0.001).

“Though our research suggests that we should investigate what’s behind the associations that we found, there is no definitive evidence yet that proves that one type of blood is better or worse for patients,” said Jason Acker, PhD, of Canadian Blood Services in Edmonton, Alberta.

“This study opens up new areas of investigation where we can really dig into the biological explanations and understand true cause and effect.”

The study was published in JAMA Internal Medicine.

Blood for transfusion
Photo by Elise Amendola

A large study has revealed an unexpected association between blood donor characteristics and transfusion recipients’ outcomes.

It is the first study to suggest that red blood cell (RBC) transfusions from younger donors or female donors may increase the risk of death in recipients.

“We need further research to confirm these findings and to look at possible biological mechanisms,” said Michaël Chassé, MD, PhD, of Université Laval in Quebec, Canada.

“One possibility is that components in the blood of younger donors or female donors may affect the immune system of the transfusion recipient.”

For this study, Dr Chassé and his colleagues linked 30,503 patients who received a transfusion at The Ottawa Hospital between October 2006 and December 2013 with their respective blood donors (80,755 donors in total).

The average age of the recipients was 66.2 years. They were followed for an average of 2.3 years, with a maximum follow-up time of 7.2 years.

The researchers found that recipients of RBCs from female donors had an 8% increased risk of death from any cause per unit transfused, when compared with recipients of RBCs from male donors. The adjusted hazard ratio (aHR) was 1.08 (95% CI, 1.06-1.09; P<0.001).

A similar increased risk of death was observed for recipients of RBCs from younger donors. When compared to recipients of RBCs from donors ages 40 to 49.9, the risk of death was higher for recipients of RBCs from donors ages 17 to 19.9 (aHR=1.08; 95% CI, 1.06-1.10; P<0.001) and recipients of RBCs from donors ages 20 to 29.9 (aHR=1.06; 95% CI, 1.04-1.09; P<0.001).

“Though our research suggests that we should investigate what’s behind the associations that we found, there is no definitive evidence yet that proves that one type of blood is better or worse for patients,” said Jason Acker, PhD, of Canadian Blood Services in Edmonton, Alberta.

“This study opens up new areas of investigation where we can really dig into the biological explanations and understand true cause and effect.”

The study was published in JAMA Internal Medicine.

Antihemophilic factor

The European Medicines Agency (EMA) has started a review of medicines containing factor VIII (FVIII) to assess the risk of inhibitor development among patients starting treatment for hemophilia A.

The agency is conducting this review because results of the SIPPET study suggested that patients are more likely to develop inhibitors if they receive FVIII products made by DNA recombinant technology rather than FVIII products derived from blood.

The EMA is evaluating data from the SIPPET study as well as all other relevant data on blood-derived and recombinant FVIII products.

The agency said it will consider the implications of these data for previously untreated patients with hemophilia A and whether there is a need for risk minimization measures or other changes to the marketing authorizations of these products.

The review will cover all medicines containing FVIII that are authorized for use within the European Union. For details on the products to be reviewed, including the different product names used in each country, visit the EMA website (Factor VIII Article-31 referral - Annex I).

The EMA’s review has been initiated at the request of the Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee, the committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

Those recommendations will then be sent to the Committee for Medicinal Products for Human Use, which is responsible for questions concerning medicines for human use and will adopt the EMA’s opinion.

Finally, the European Commission will adopt a legally binding decision applicable in all member states of the European Union.

Antihemophilic factor

The European Medicines Agency (EMA) has started a review of medicines containing factor VIII (FVIII) to assess the risk of inhibitor development among patients starting treatment for hemophilia A.

The agency is conducting this review because results of the SIPPET study suggested that patients are more likely to develop inhibitors if they receive FVIII products made by DNA recombinant technology rather than FVIII products derived from blood.

The EMA is evaluating data from the SIPPET study as well as all other relevant data on blood-derived and recombinant FVIII products.

The agency said it will consider the implications of these data for previously untreated patients with hemophilia A and whether there is a need for risk minimization measures or other changes to the marketing authorizations of these products.

The review will cover all medicines containing FVIII that are authorized for use within the European Union. For details on the products to be reviewed, including the different product names used in each country, visit the EMA website (Factor VIII Article-31 referral - Annex I).

The EMA’s review has been initiated at the request of the Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee, the committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

Those recommendations will then be sent to the Committee for Medicinal Products for Human Use, which is responsible for questions concerning medicines for human use and will adopt the EMA’s opinion.

Finally, the European Commission will adopt a legally binding decision applicable in all member states of the European Union.

Antihemophilic factor

The European Medicines Agency (EMA) has started a review of medicines containing factor VIII (FVIII) to assess the risk of inhibitor development among patients starting treatment for hemophilia A.

The agency is conducting this review because results of the SIPPET study suggested that patients are more likely to develop inhibitors if they receive FVIII products made by DNA recombinant technology rather than FVIII products derived from blood.

The EMA is evaluating data from the SIPPET study as well as all other relevant data on blood-derived and recombinant FVIII products.

The agency said it will consider the implications of these data for previously untreated patients with hemophilia A and whether there is a need for risk minimization measures or other changes to the marketing authorizations of these products.

The review will cover all medicines containing FVIII that are authorized for use within the European Union. For details on the products to be reviewed, including the different product names used in each country, visit the EMA website (Factor VIII Article-31 referral - Annex I).

The EMA’s review has been initiated at the request of the Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee, the committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations.

Those recommendations will then be sent to the Committee for Medicinal Products for Human Use, which is responsible for questions concerning medicines for human use and will adopt the EMA’s opinion.

Finally, the European Commission will adopt a legally binding decision applicable in all member states of the European Union.

Mouse embryo

Photo by Matthias Zepper

Researchers may have identified the cells responsible for MLL-AF4+ infant B-cell acute lymphoblastic leukemia, according to a paper published in Cell Reports.

The team analyzed mouse embryos and discovered a “window of opportunity” during which a pre-leukemic state can take hold.

They also found evidence to suggest this pre-leukemic state is driven by lymphoid-primed multipotent progenitor cells.

“One of the most common and aggressive types of infant blood cancer is associated with the MLL-AF4 fusion gene, which arises during pregnancy,” said study author Katrin Ottersbach, PhD, of the University of Edinburgh in the UK.

“One of the main impediments to improving the survival rates in infants is the lack of knowledge on where and when during development this mutation arises and how it affects the developing blood system of the baby.”

To gain some insight, Dr Ottersbach and her colleagues bred mice where one parent carries an inactive form of the MLL-AF4 fusion gene and the other parent expresses a gene for an enzyme that activates the fusion gene.

The embryos from this pairing entered a pre-leukemic state between days 12 and 14. The researchers found that MLL-AF4 imparted enhanced B lymphoid potential and increased repopulation and self-renewal capacity during this time.

Further investigation suggested that lymphoid-primed multipotent progenitor cells were the major contributors to the enhanced B lymphoid output and may therefore be the cells of origin.

The researchers noted that the mice did not actually develop infant leukemia, so more research is needed to identify the events required for progression to MLL-AF4+ infant B-cell acute lymphoblastic leukemia.

“Our findings reveal the first changes that take place in blood development caused by the MLL-AF4 mutation during a pre-cancerous state,” Dr Ottersbach said. “This has increased our knowledge on how this aggressive disease develops and will help identify early signs of disease and points for therapeutic intervention.”

Mouse embryo

Photo by Matthias Zepper

Researchers may have identified the cells responsible for MLL-AF4+ infant B-cell acute lymphoblastic leukemia, according to a paper published in Cell Reports.

The team analyzed mouse embryos and discovered a “window of opportunity” during which a pre-leukemic state can take hold.

They also found evidence to suggest this pre-leukemic state is driven by lymphoid-primed multipotent progenitor cells.

“One of the most common and aggressive types of infant blood cancer is associated with the MLL-AF4 fusion gene, which arises during pregnancy,” said study author Katrin Ottersbach, PhD, of the University of Edinburgh in the UK.

“One of the main impediments to improving the survival rates in infants is the lack of knowledge on where and when during development this mutation arises and how it affects the developing blood system of the baby.”

To gain some insight, Dr Ottersbach and her colleagues bred mice where one parent carries an inactive form of the MLL-AF4 fusion gene and the other parent expresses a gene for an enzyme that activates the fusion gene.

The embryos from this pairing entered a pre-leukemic state between days 12 and 14. The researchers found that MLL-AF4 imparted enhanced B lymphoid potential and increased repopulation and self-renewal capacity during this time.

Further investigation suggested that lymphoid-primed multipotent progenitor cells were the major contributors to the enhanced B lymphoid output and may therefore be the cells of origin.

The researchers noted that the mice did not actually develop infant leukemia, so more research is needed to identify the events required for progression to MLL-AF4+ infant B-cell acute lymphoblastic leukemia.

“Our findings reveal the first changes that take place in blood development caused by the MLL-AF4 mutation during a pre-cancerous state,” Dr Ottersbach said. “This has increased our knowledge on how this aggressive disease develops and will help identify early signs of disease and points for therapeutic intervention.”

Mouse embryo

Photo by Matthias Zepper

Researchers may have identified the cells responsible for MLL-AF4+ infant B-cell acute lymphoblastic leukemia, according to a paper published in Cell Reports.

The team analyzed mouse embryos and discovered a “window of opportunity” during which a pre-leukemic state can take hold.

They also found evidence to suggest this pre-leukemic state is driven by lymphoid-primed multipotent progenitor cells.

“One of the most common and aggressive types of infant blood cancer is associated with the MLL-AF4 fusion gene, which arises during pregnancy,” said study author Katrin Ottersbach, PhD, of the University of Edinburgh in the UK.

“One of the main impediments to improving the survival rates in infants is the lack of knowledge on where and when during development this mutation arises and how it affects the developing blood system of the baby.”

To gain some insight, Dr Ottersbach and her colleagues bred mice where one parent carries an inactive form of the MLL-AF4 fusion gene and the other parent expresses a gene for an enzyme that activates the fusion gene.

The embryos from this pairing entered a pre-leukemic state between days 12 and 14. The researchers found that MLL-AF4 imparted enhanced B lymphoid potential and increased repopulation and self-renewal capacity during this time.

Further investigation suggested that lymphoid-primed multipotent progenitor cells were the major contributors to the enhanced B lymphoid output and may therefore be the cells of origin.

The researchers noted that the mice did not actually develop infant leukemia, so more research is needed to identify the events required for progression to MLL-AF4+ infant B-cell acute lymphoblastic leukemia.

“Our findings reveal the first changes that take place in blood development caused by the MLL-AF4 mutation during a pre-cancerous state,” Dr Ottersbach said. “This has increased our knowledge on how this aggressive disease develops and will help identify early signs of disease and points for therapeutic intervention.”

 

 

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences, Inc.

 

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed its review of the PI3Kδ inhibitor idelalisib (Zyedelig) and concluded that the drug’s benefits outweigh its risks in the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma.

However, the PRAC also confirmed that the drug increases the risk of serious infections, including Pneumocystis jirovecii pneumonia.

And the committee updated its previous recommendations to manage this risk.

The PRAC’s recommendations will now be sent to the Committee for Medicinal Products for Human Use, which will adopt the EMA’s final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all member states of the European Union (EU).

About idelalisib

In the EU, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients unsuitable for chemo-immunotherapy.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

About the review

The PRAC’s review of idelalisib began after a higher rate of serious adverse events, including deaths, was seen in 3 clinical trials evaluating the addition of idelalisib to standard therapy in first-line CLL and relapsed indolent non-Hodgkin lymphoma (NHL).

Most of the deaths were related to infections such as Pneumocystis jirovecii pneumonia and cytomegalovirus infection. Other excess deaths were related mainly to respiratory events.

The NHL studies (NCT01732926 and NCT01732913) included patients with disease characteristics different from those covered by the currently approved indications for idelalisib and investigated combinations of drugs that are not currently approved in the EU—idelalisib plus rituximab for NHL and idelalisib plus bendamustine and rituximab for NHL.

The CLL trial (NCT01980888) involved patients who had not received previous treatment, some of whom had the 17p deletion or TP53 mutation. However, the trial also investigated a combination of drugs not currently approved in the EU—idelalisib plus bendamustine and rituximab.

PRAC’s recommendations

The PRAC noted that, although the aforementioned trials did not all use idelalisib as currently authorized, the risk of serious infection is considered relevant to the authorized use.

Therefore, the PRAC recommends that all patients treated with idelalisib receive antibiotics to prevent Pneumocystis jirovecii pneumonia during treatment and for up to 2 to 6 months after treatment has stopped.

Patients should also be monitored for infection and have regular blood tests for white cell counts because low counts can increase their risk of infection.

Furthermore, idelalisib should not be started in patients with a generalized infection.

At the beginning of its review, the PRAC had said idelalisib should not be started in patients with previously untreated CLL and 17p deletion or TP53 mutation.

Now, the PRAC has concluded that idelalisib can be initiated in these patients, provided they cannot take any alternative treatment and that the recommended measures to prevent infection are followed.

 

 

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences, Inc.

 

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed its review of the PI3Kδ inhibitor idelalisib (Zyedelig) and concluded that the drug’s benefits outweigh its risks in the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma.

However, the PRAC also confirmed that the drug increases the risk of serious infections, including Pneumocystis jirovecii pneumonia.

And the committee updated its previous recommendations to manage this risk.

The PRAC’s recommendations will now be sent to the Committee for Medicinal Products for Human Use, which will adopt the EMA’s final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all member states of the European Union (EU).

About idelalisib

In the EU, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients unsuitable for chemo-immunotherapy.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

About the review

The PRAC’s review of idelalisib began after a higher rate of serious adverse events, including deaths, was seen in 3 clinical trials evaluating the addition of idelalisib to standard therapy in first-line CLL and relapsed indolent non-Hodgkin lymphoma (NHL).

Most of the deaths were related to infections such as Pneumocystis jirovecii pneumonia and cytomegalovirus infection. Other excess deaths were related mainly to respiratory events.

The NHL studies (NCT01732926 and NCT01732913) included patients with disease characteristics different from those covered by the currently approved indications for idelalisib and investigated combinations of drugs that are not currently approved in the EU—idelalisib plus rituximab for NHL and idelalisib plus bendamustine and rituximab for NHL.

The CLL trial (NCT01980888) involved patients who had not received previous treatment, some of whom had the 17p deletion or TP53 mutation. However, the trial also investigated a combination of drugs not currently approved in the EU—idelalisib plus bendamustine and rituximab.

PRAC’s recommendations

The PRAC noted that, although the aforementioned trials did not all use idelalisib as currently authorized, the risk of serious infection is considered relevant to the authorized use.

Therefore, the PRAC recommends that all patients treated with idelalisib receive antibiotics to prevent Pneumocystis jirovecii pneumonia during treatment and for up to 2 to 6 months after treatment has stopped.

Patients should also be monitored for infection and have regular blood tests for white cell counts because low counts can increase their risk of infection.

Furthermore, idelalisib should not be started in patients with a generalized infection.

At the beginning of its review, the PRAC had said idelalisib should not be started in patients with previously untreated CLL and 17p deletion or TP53 mutation.

Now, the PRAC has concluded that idelalisib can be initiated in these patients, provided they cannot take any alternative treatment and that the recommended measures to prevent infection are followed.

 

 

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences, Inc.

 

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed its review of the PI3Kδ inhibitor idelalisib (Zyedelig) and concluded that the drug’s benefits outweigh its risks in the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma.

However, the PRAC also confirmed that the drug increases the risk of serious infections, including Pneumocystis jirovecii pneumonia.

And the committee updated its previous recommendations to manage this risk.

The PRAC’s recommendations will now be sent to the Committee for Medicinal Products for Human Use, which will adopt the EMA’s final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all member states of the European Union (EU).

About idelalisib

In the EU, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients unsuitable for chemo-immunotherapy.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

About the review

The PRAC’s review of idelalisib began after a higher rate of serious adverse events, including deaths, was seen in 3 clinical trials evaluating the addition of idelalisib to standard therapy in first-line CLL and relapsed indolent non-Hodgkin lymphoma (NHL).

Most of the deaths were related to infections such as Pneumocystis jirovecii pneumonia and cytomegalovirus infection. Other excess deaths were related mainly to respiratory events.

The NHL studies (NCT01732926 and NCT01732913) included patients with disease characteristics different from those covered by the currently approved indications for idelalisib and investigated combinations of drugs that are not currently approved in the EU—idelalisib plus rituximab for NHL and idelalisib plus bendamustine and rituximab for NHL.

The CLL trial (NCT01980888) involved patients who had not received previous treatment, some of whom had the 17p deletion or TP53 mutation. However, the trial also investigated a combination of drugs not currently approved in the EU—idelalisib plus bendamustine and rituximab.

PRAC’s recommendations

The PRAC noted that, although the aforementioned trials did not all use idelalisib as currently authorized, the risk of serious infection is considered relevant to the authorized use.

Therefore, the PRAC recommends that all patients treated with idelalisib receive antibiotics to prevent Pneumocystis jirovecii pneumonia during treatment and for up to 2 to 6 months after treatment has stopped.

Patients should also be monitored for infection and have regular blood tests for white cell counts because low counts can increase their risk of infection.

Furthermore, idelalisib should not be started in patients with a generalized infection.

At the beginning of its review, the PRAC had said idelalisib should not be started in patients with previously untreated CLL and 17p deletion or TP53 mutation.

Now, the PRAC has concluded that idelalisib can be initiated in these patients, provided they cannot take any alternative treatment and that the recommended measures to prevent infection are followed.

T cells
Image from UNSW

Update: The hold on this trial has been lifted. Click here for additional details.

A trial of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 has been placed on clinical hold following 3 patient deaths.

The trial, known as ROCKET, is a phase 2 study of adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The US Food and Drug Administration (FDA) placed a hold on the trial after 3 patients died of cerebral edema.

All 3 patients had received conditioning with fludarabine, and Juno Therapeutics, the company developing JCAR015, believes this may have caused the patients’ deaths.

Patients enrolled on the ROCKET trial previously received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy.

The addition of fludarabine to conditioning had been shown to increase the efficacy of 2 of Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials. 

“However, since adding fludarabine to the preconditioning on the ROCKET trial, we have seen an increase in the incidence of severe neurotoxicity, which has, unfortunately, included 2 patient deaths that occurred last week from cerebral edema that appeared to be treatment-related,” Hans Bishop, Juno’s president and chief executive officer, said in a conference call.

“After the first of these 2 deaths, we immediately paused the trial for an internal review and review with our Data Safety Monitoring Board [DSMB] and the FDA. There was also 1 previous death from cerebral edema on the trial in May. After a review of that event, we, along with the FDA and our DSMB, concluded there were confounding factors, and a change in our plans at the time was not warranted.”

After the more recent deaths, Juno investigated several factors that could have contributed, including the conditioning regimen, patient characteristics, toxicity management, product characteristics, and cell dose.

“Although more than 1 factor may have contributed, based on our review of the data available . . . , we believe the addition of fludarabine, when combined with JCAR015, is the most likely and the most appropriately modifiable factor,” Bishop said.

“Indeed, with cy[clophosphamide] alone, which we have used in the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths, and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan-Kettering experience [phase 1 trial of JCAR015].”

Therefore, Juno has proposed continuing the ROCKET trial using conditioning with cyclophosphamide alone.

In response to this request, the FDA has requested that Juno submit:

• A revised patient informed consent form
• A revised investigator brochure
• A revised trial protocol
• A copy of a presentation the company made to the FDA.

The FDA said it will expedite the review of these documents and expects to complete the review within 30 days of receiving them.

If the clinical hold on the ROCKET trial is lifted, Juno plans to continue the trial. However, the hold will likely impact the company’s goal of gaining FDA approval for JCAR015 in 2017.

Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates are not affected by the clinical hold placed on ROCKET.

ROCKET is not the first trial of JCAR015 to be placed on hold. The phase 1 trial of the therapy was placed on clinical hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

T cells
Image from UNSW

Update: The hold on this trial has been lifted. Click here for additional details.

A trial of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 has been placed on clinical hold following 3 patient deaths.

The trial, known as ROCKET, is a phase 2 study of adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The US Food and Drug Administration (FDA) placed a hold on the trial after 3 patients died of cerebral edema.

All 3 patients had received conditioning with fludarabine, and Juno Therapeutics, the company developing JCAR015, believes this may have caused the patients’ deaths.

Patients enrolled on the ROCKET trial previously received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy.

The addition of fludarabine to conditioning had been shown to increase the efficacy of 2 of Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials. 

“However, since adding fludarabine to the preconditioning on the ROCKET trial, we have seen an increase in the incidence of severe neurotoxicity, which has, unfortunately, included 2 patient deaths that occurred last week from cerebral edema that appeared to be treatment-related,” Hans Bishop, Juno’s president and chief executive officer, said in a conference call.

“After the first of these 2 deaths, we immediately paused the trial for an internal review and review with our Data Safety Monitoring Board [DSMB] and the FDA. There was also 1 previous death from cerebral edema on the trial in May. After a review of that event, we, along with the FDA and our DSMB, concluded there were confounding factors, and a change in our plans at the time was not warranted.”

After the more recent deaths, Juno investigated several factors that could have contributed, including the conditioning regimen, patient characteristics, toxicity management, product characteristics, and cell dose.

“Although more than 1 factor may have contributed, based on our review of the data available . . . , we believe the addition of fludarabine, when combined with JCAR015, is the most likely and the most appropriately modifiable factor,” Bishop said.

“Indeed, with cy[clophosphamide] alone, which we have used in the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths, and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan-Kettering experience [phase 1 trial of JCAR015].”

Therefore, Juno has proposed continuing the ROCKET trial using conditioning with cyclophosphamide alone.

In response to this request, the FDA has requested that Juno submit:

• A revised patient informed consent form
• A revised investigator brochure
• A revised trial protocol
• A copy of a presentation the company made to the FDA.

The FDA said it will expedite the review of these documents and expects to complete the review within 30 days of receiving them.

If the clinical hold on the ROCKET trial is lifted, Juno plans to continue the trial. However, the hold will likely impact the company’s goal of gaining FDA approval for JCAR015 in 2017.

Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates are not affected by the clinical hold placed on ROCKET.

ROCKET is not the first trial of JCAR015 to be placed on hold. The phase 1 trial of the therapy was placed on clinical hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

T cells
Image from UNSW

Update: The hold on this trial has been lifted. Click here for additional details.

A trial of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 has been placed on clinical hold following 3 patient deaths.

The trial, known as ROCKET, is a phase 2 study of adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The US Food and Drug Administration (FDA) placed a hold on the trial after 3 patients died of cerebral edema.

All 3 patients had received conditioning with fludarabine, and Juno Therapeutics, the company developing JCAR015, believes this may have caused the patients’ deaths.

Patients enrolled on the ROCKET trial previously received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy.

The addition of fludarabine to conditioning had been shown to increase the efficacy of 2 of Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials. 

“However, since adding fludarabine to the preconditioning on the ROCKET trial, we have seen an increase in the incidence of severe neurotoxicity, which has, unfortunately, included 2 patient deaths that occurred last week from cerebral edema that appeared to be treatment-related,” Hans Bishop, Juno’s president and chief executive officer, said in a conference call.

“After the first of these 2 deaths, we immediately paused the trial for an internal review and review with our Data Safety Monitoring Board [DSMB] and the FDA. There was also 1 previous death from cerebral edema on the trial in May. After a review of that event, we, along with the FDA and our DSMB, concluded there were confounding factors, and a change in our plans at the time was not warranted.”

After the more recent deaths, Juno investigated several factors that could have contributed, including the conditioning regimen, patient characteristics, toxicity management, product characteristics, and cell dose.

“Although more than 1 factor may have contributed, based on our review of the data available . . . , we believe the addition of fludarabine, when combined with JCAR015, is the most likely and the most appropriately modifiable factor,” Bishop said.

“Indeed, with cy[clophosphamide] alone, which we have used in the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths, and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan-Kettering experience [phase 1 trial of JCAR015].”

Therefore, Juno has proposed continuing the ROCKET trial using conditioning with cyclophosphamide alone.

In response to this request, the FDA has requested that Juno submit:

• A revised patient informed consent form
• A revised investigator brochure
• A revised trial protocol
• A copy of a presentation the company made to the FDA.

The FDA said it will expedite the review of these documents and expects to complete the review within 30 days of receiving them.

If the clinical hold on the ROCKET trial is lifted, Juno plans to continue the trial. However, the hold will likely impact the company’s goal of gaining FDA approval for JCAR015 in 2017.

Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates are not affected by the clinical hold placed on ROCKET.

ROCKET is not the first trial of JCAR015 to be placed on hold. The phase 1 trial of the therapy was placed on clinical hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

Drug release in a cancer cell

Image from PNAS

A study published in Cell has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors and could therefore be used to learn how cancers are likely to respond to new drugs.

Researchers believe this discovery could help advance personalized cancer medicine by leading to results that help doctors predict the best available drugs or the most suitable clinical trials for each individual patient.

“We need better ways to figure out which groups of patients are more likely to respond to a new drug before we run complex and expensive clinical trials,” said study author Ultan McDermott, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“Our research shows that cancer cell lines do capture the molecular alterations found in tumors and so can be predictive of how a tumor will respond to a drug. This means the cell lines could tell us much more about how a tumor is likely to respond to a new drug before we try to test it in patients. We hope this information will ultimately help in the design of clinical trials that target those patients with the greatest likelihood of benefiting from treatment.”

The researchers said this is the first systematic, large-scale study to combine molecular data from patients, cancer cell lines, and drug sensitivity.

For the study, the team looked at genetic mutations known to cause cancer in more than 11,000 patient samples of 29 different cancer types, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, and multiple myeloma.

The researchers built a catalogue of the genetic changes that cause cancer in patients and mapped these alterations onto 1000 cancer cell lines. Next, they tested the cell lines for sensitivity to 265 different cancer drugs to understand which of these changes affect sensitivity.

This revealed that the majority of molecular abnormalities found in patients’ cancers are also found in cancer cells in the laboratory.

The work also showed that many of the molecular abnormalities detected in the thousands of patient samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.

The results suggest cancer cell lines could be better exploited to learn which drugs offer the most effective treatment to which patients.

“If a cell line has the same genetic features as a patient’s tumor, and that cell line responded to a specific drug, we can focus new research on this finding,” said study author Francesco Iorio, PhD, of the European Bioinformatics Institute in Cambridge, UK.

“This could ultimately help assign cancer patients into more precise groups based on how likely they are to respond to therapy. This resource can really help cancer research. Most importantly, it can be used to create tools for doctors to select a clinical trial which is most promising for their cancer patient. That is still a way off, but we are heading in the right direction.”

Drug release in a cancer cell

Image from PNAS

A study published in Cell has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors and could therefore be used to learn how cancers are likely to respond to new drugs.

Researchers believe this discovery could help advance personalized cancer medicine by leading to results that help doctors predict the best available drugs or the most suitable clinical trials for each individual patient.

“We need better ways to figure out which groups of patients are more likely to respond to a new drug before we run complex and expensive clinical trials,” said study author Ultan McDermott, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“Our research shows that cancer cell lines do capture the molecular alterations found in tumors and so can be predictive of how a tumor will respond to a drug. This means the cell lines could tell us much more about how a tumor is likely to respond to a new drug before we try to test it in patients. We hope this information will ultimately help in the design of clinical trials that target those patients with the greatest likelihood of benefiting from treatment.”

The researchers said this is the first systematic, large-scale study to combine molecular data from patients, cancer cell lines, and drug sensitivity.

For the study, the team looked at genetic mutations known to cause cancer in more than 11,000 patient samples of 29 different cancer types, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, and multiple myeloma.

The researchers built a catalogue of the genetic changes that cause cancer in patients and mapped these alterations onto 1000 cancer cell lines. Next, they tested the cell lines for sensitivity to 265 different cancer drugs to understand which of these changes affect sensitivity.

This revealed that the majority of molecular abnormalities found in patients’ cancers are also found in cancer cells in the laboratory.

The work also showed that many of the molecular abnormalities detected in the thousands of patient samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.

The results suggest cancer cell lines could be better exploited to learn which drugs offer the most effective treatment to which patients.

“If a cell line has the same genetic features as a patient’s tumor, and that cell line responded to a specific drug, we can focus new research on this finding,” said study author Francesco Iorio, PhD, of the European Bioinformatics Institute in Cambridge, UK.

“This could ultimately help assign cancer patients into more precise groups based on how likely they are to respond to therapy. This resource can really help cancer research. Most importantly, it can be used to create tools for doctors to select a clinical trial which is most promising for their cancer patient. That is still a way off, but we are heading in the right direction.”

Drug release in a cancer cell

Image from PNAS

A study published in Cell has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors and could therefore be used to learn how cancers are likely to respond to new drugs.

Researchers believe this discovery could help advance personalized cancer medicine by leading to results that help doctors predict the best available drugs or the most suitable clinical trials for each individual patient.

“We need better ways to figure out which groups of patients are more likely to respond to a new drug before we run complex and expensive clinical trials,” said study author Ultan McDermott, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“Our research shows that cancer cell lines do capture the molecular alterations found in tumors and so can be predictive of how a tumor will respond to a drug. This means the cell lines could tell us much more about how a tumor is likely to respond to a new drug before we try to test it in patients. We hope this information will ultimately help in the design of clinical trials that target those patients with the greatest likelihood of benefiting from treatment.”

The researchers said this is the first systematic, large-scale study to combine molecular data from patients, cancer cell lines, and drug sensitivity.

For the study, the team looked at genetic mutations known to cause cancer in more than 11,000 patient samples of 29 different cancer types, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, and multiple myeloma.

The researchers built a catalogue of the genetic changes that cause cancer in patients and mapped these alterations onto 1000 cancer cell lines. Next, they tested the cell lines for sensitivity to 265 different cancer drugs to understand which of these changes affect sensitivity.

This revealed that the majority of molecular abnormalities found in patients’ cancers are also found in cancer cells in the laboratory.

The work also showed that many of the molecular abnormalities detected in the thousands of patient samples can, both individually and in combination, have a strong effect on whether a particular drug affects a cancer cell’s survival.

The results suggest cancer cell lines could be better exploited to learn which drugs offer the most effective treatment to which patients.

“If a cell line has the same genetic features as a patient’s tumor, and that cell line responded to a specific drug, we can focus new research on this finding,” said study author Francesco Iorio, PhD, of the European Bioinformatics Institute in Cambridge, UK.

“This could ultimately help assign cancer patients into more precise groups based on how likely they are to respond to therapy. This resource can really help cancer research. Most importantly, it can be used to create tools for doctors to select a clinical trial which is most promising for their cancer patient. That is still a way off, but we are heading in the right direction.”

AML cells

Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).

Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.

The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.

This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.

The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.

So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.

“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.

“If the gene is defective, cancer cells get more energy to use for proliferation.”

Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.

And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.

“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.

“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”

AML cells

Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).

Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.

The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.

This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.

The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.

So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.

“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.

“If the gene is defective, cancer cells get more energy to use for proliferation.”

Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.

And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.

“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.

“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”

AML cells

Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).

Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.

The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.

This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.

The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.

So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.

“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.

“If the gene is defective, cancer cells get more energy to use for proliferation.”

Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.

And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.

Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.

“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.

“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”

Thrombus

Image by Kevin MacKenzie

Researchers say they have developed a thrombolytic material that can be condensed on a blood clot by means of a magnetic field.

Experiments suggest the material can dissolve clots up to 4000 times more efficiently than thrombolytic agents currently in use.

Vladimir Vinogradov, PhD, of ITMO University in St Petersburg, Russia, and his colleagues described the material in Scientific Reports.

“We prepared a thrombolytic colloid and tested its effects on an artificial blood clot obtained from plasma and blood of humans and thrombus extracted from patients,” Dr Vinogradov said.

“The results may soon allow us to try out the new thrombolytic system on mammals. Now, we are preparing for preclinical studies.”

Specifically, Dr Vinogradov and his colleagues produced a composite material that can deliver thrombolytic enzymes in a targeted manner. The material is composed of a porous magnetite framework and molecules of urokinase, an enzyme frequently used as a thrombolytic agent.

The composite can be used to create thrombolytic coating for artificial blood vessels and stable injectable solutions made of nanoparticles that can be localized near the clot by means of an external magnetic field.

The magnetite framework also protects enzymes from various inhibitors that are present in the blood and can deactivate thrombolytic medications.

“Usually, in order to achieve a prolonged effect for such drugs, the enzyme is placed inside a polymeric matrix,” said study author Andrey Drozdov, of ITMO University.

“The enzyme is then gradually released from the matrix and eventually loses all activity. We, on the other hand, experimentally demonstrated that enzymes protected using our approach do not lose therapeutic properties over extended periods of time and even after repeated use. The rate at which the new drug can dissolve the clot outperforms unprotected enzymes by about 4000 times.”

The researchers also believe the material is safe for humans because it is made of components that are already approved for intravenous injection.

Thrombus

Image by Kevin MacKenzie

Researchers say they have developed a thrombolytic material that can be condensed on a blood clot by means of a magnetic field.

Experiments suggest the material can dissolve clots up to 4000 times more efficiently than thrombolytic agents currently in use.

Vladimir Vinogradov, PhD, of ITMO University in St Petersburg, Russia, and his colleagues described the material in Scientific Reports.

“We prepared a thrombolytic colloid and tested its effects on an artificial blood clot obtained from plasma and blood of humans and thrombus extracted from patients,” Dr Vinogradov said.

“The results may soon allow us to try out the new thrombolytic system on mammals. Now, we are preparing for preclinical studies.”

Specifically, Dr Vinogradov and his colleagues produced a composite material that can deliver thrombolytic enzymes in a targeted manner. The material is composed of a porous magnetite framework and molecules of urokinase, an enzyme frequently used as a thrombolytic agent.

The composite can be used to create thrombolytic coating for artificial blood vessels and stable injectable solutions made of nanoparticles that can be localized near the clot by means of an external magnetic field.

The magnetite framework also protects enzymes from various inhibitors that are present in the blood and can deactivate thrombolytic medications.

“Usually, in order to achieve a prolonged effect for such drugs, the enzyme is placed inside a polymeric matrix,” said study author Andrey Drozdov, of ITMO University.

“The enzyme is then gradually released from the matrix and eventually loses all activity. We, on the other hand, experimentally demonstrated that enzymes protected using our approach do not lose therapeutic properties over extended periods of time and even after repeated use. The rate at which the new drug can dissolve the clot outperforms unprotected enzymes by about 4000 times.”

The researchers also believe the material is safe for humans because it is made of components that are already approved for intravenous injection.

Thrombus

Image by Kevin MacKenzie

Researchers say they have developed a thrombolytic material that can be condensed on a blood clot by means of a magnetic field.

Experiments suggest the material can dissolve clots up to 4000 times more efficiently than thrombolytic agents currently in use.

Vladimir Vinogradov, PhD, of ITMO University in St Petersburg, Russia, and his colleagues described the material in Scientific Reports.

“We prepared a thrombolytic colloid and tested its effects on an artificial blood clot obtained from plasma and blood of humans and thrombus extracted from patients,” Dr Vinogradov said.

“The results may soon allow us to try out the new thrombolytic system on mammals. Now, we are preparing for preclinical studies.”

Specifically, Dr Vinogradov and his colleagues produced a composite material that can deliver thrombolytic enzymes in a targeted manner. The material is composed of a porous magnetite framework and molecules of urokinase, an enzyme frequently used as a thrombolytic agent.

The composite can be used to create thrombolytic coating for artificial blood vessels and stable injectable solutions made of nanoparticles that can be localized near the clot by means of an external magnetic field.

The magnetite framework also protects enzymes from various inhibitors that are present in the blood and can deactivate thrombolytic medications.

“Usually, in order to achieve a prolonged effect for such drugs, the enzyme is placed inside a polymeric matrix,” said study author Andrey Drozdov, of ITMO University.

“The enzyme is then gradually released from the matrix and eventually loses all activity. We, on the other hand, experimentally demonstrated that enzymes protected using our approach do not lose therapeutic properties over extended periods of time and even after repeated use. The rate at which the new drug can dissolve the clot outperforms unprotected enzymes by about 4000 times.”

The researchers also believe the material is safe for humans because it is made of components that are already approved for intravenous injection.