Anemia

 

The Food and Drug Administration no longer requires certification of doctors and hospitals to prescribe epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp) for chemotherapy anemia.

A Risk Evaluation and Mitigation Strategy (REMS) program was put in place in 2011 to make sure that the benefits of erythropoiesis-stimulating agents (ESAs) outweighed the risks when prescribed. Under the program, providers were required to become certified in the ESA REMS and to demonstrate that each patient had received counseling on the benefits and risks of the therapies prior to use.

The FDA has determined the REMS is no longer necessary, based on survey data submitted by Amgen, marketer of Epogen and Aranesp, and on additional FDA analyses to understand the impact that various regulatory and other actions have had on the use of ESAs.

Amgen’s prescriber surveys demonstrated “acceptable knowledge” of the need to counsel patients about the risks. Utilization data indicated “appropriate prescribing” as an alternative to transfusion.

In addition, in an evaluation of the impact of multiple regulatory actions, the FDA determined that full implementation of the ESA REMS in 2011 had minimal impact on trends in ESA utilization metrics, the FDA wrote.

The FDA concluded that regulatory actions and label changes – and the cut in payments for nonrenal indications from the Center for Medicare & Medicaid Services – were enough to reduce overuse in chemotherapy.

However, while the REMS is no longer necessary, the FDA says serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with these drugs remain and health care providers should continue to discuss the risks and benefits of using ESAs with each patient before initiating use.
 

[email protected]

 

The Food and Drug Administration no longer requires certification of doctors and hospitals to prescribe epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp) for chemotherapy anemia.

A Risk Evaluation and Mitigation Strategy (REMS) program was put in place in 2011 to make sure that the benefits of erythropoiesis-stimulating agents (ESAs) outweighed the risks when prescribed. Under the program, providers were required to become certified in the ESA REMS and to demonstrate that each patient had received counseling on the benefits and risks of the therapies prior to use.

The FDA has determined the REMS is no longer necessary, based on survey data submitted by Amgen, marketer of Epogen and Aranesp, and on additional FDA analyses to understand the impact that various regulatory and other actions have had on the use of ESAs.

Amgen’s prescriber surveys demonstrated “acceptable knowledge” of the need to counsel patients about the risks. Utilization data indicated “appropriate prescribing” as an alternative to transfusion.

In addition, in an evaluation of the impact of multiple regulatory actions, the FDA determined that full implementation of the ESA REMS in 2011 had minimal impact on trends in ESA utilization metrics, the FDA wrote.

The FDA concluded that regulatory actions and label changes – and the cut in payments for nonrenal indications from the Center for Medicare & Medicaid Services – were enough to reduce overuse in chemotherapy.

However, while the REMS is no longer necessary, the FDA says serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with these drugs remain and health care providers should continue to discuss the risks and benefits of using ESAs with each patient before initiating use.
 

[email protected]

 

The Food and Drug Administration no longer requires certification of doctors and hospitals to prescribe epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp) for chemotherapy anemia.

A Risk Evaluation and Mitigation Strategy (REMS) program was put in place in 2011 to make sure that the benefits of erythropoiesis-stimulating agents (ESAs) outweighed the risks when prescribed. Under the program, providers were required to become certified in the ESA REMS and to demonstrate that each patient had received counseling on the benefits and risks of the therapies prior to use.

The FDA has determined the REMS is no longer necessary, based on survey data submitted by Amgen, marketer of Epogen and Aranesp, and on additional FDA analyses to understand the impact that various regulatory and other actions have had on the use of ESAs.

Amgen’s prescriber surveys demonstrated “acceptable knowledge” of the need to counsel patients about the risks. Utilization data indicated “appropriate prescribing” as an alternative to transfusion.

In addition, in an evaluation of the impact of multiple regulatory actions, the FDA determined that full implementation of the ESA REMS in 2011 had minimal impact on trends in ESA utilization metrics, the FDA wrote.

The FDA concluded that regulatory actions and label changes – and the cut in payments for nonrenal indications from the Center for Medicare & Medicaid Services – were enough to reduce overuse in chemotherapy.

However, while the REMS is no longer necessary, the FDA says serious risks of shortened overall survival and/or increased risk of tumor progression or recurrence associated with these drugs remain and health care providers should continue to discuss the risks and benefits of using ESAs with each patient before initiating use.
 

[email protected]

Red blood cells

The US Food and Drug Administration (FDA) has determined that the risk evaluation and mitigation strategy (REMS) for erythropoiesis-stimulating agents (ESAs) is no longer necessary.

The REMS was limited to the use of epoetin alfa (marketed as Epogen and Procrit) and darbepoetin alfa (marketed as Aranesp) to treat patients with anemia due to myelosuppressive chemotherapy.

The FDA said the REMS is no longer necessary to ensure that the benefits of Epogen/Procrit and Aranesp outweigh the risks these drugs pose, which include shortened overall survival and an increased risk of tumor progression or recurrence in patients with cancer.

The FDA has released the REMS requirements for these ESAs and said the risks the drugs pose can be communicated by the current product prescribing information.

The FDA decided the REMS is no longer needed based on its own analyses and an evaluation of the REMS assessment submitted by Amgen, Inc., the company that markets Epogen/Procrit and Aranesp.

Details on the analyses and evaluation are available from the following page on the FDA website: Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp).

Red blood cells

The US Food and Drug Administration (FDA) has determined that the risk evaluation and mitigation strategy (REMS) for erythropoiesis-stimulating agents (ESAs) is no longer necessary.

The REMS was limited to the use of epoetin alfa (marketed as Epogen and Procrit) and darbepoetin alfa (marketed as Aranesp) to treat patients with anemia due to myelosuppressive chemotherapy.

The FDA said the REMS is no longer necessary to ensure that the benefits of Epogen/Procrit and Aranesp outweigh the risks these drugs pose, which include shortened overall survival and an increased risk of tumor progression or recurrence in patients with cancer.

The FDA has released the REMS requirements for these ESAs and said the risks the drugs pose can be communicated by the current product prescribing information.

The FDA decided the REMS is no longer needed based on its own analyses and an evaluation of the REMS assessment submitted by Amgen, Inc., the company that markets Epogen/Procrit and Aranesp.

Details on the analyses and evaluation are available from the following page on the FDA website: Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp).

Red blood cells

The US Food and Drug Administration (FDA) has determined that the risk evaluation and mitigation strategy (REMS) for erythropoiesis-stimulating agents (ESAs) is no longer necessary.

The REMS was limited to the use of epoetin alfa (marketed as Epogen and Procrit) and darbepoetin alfa (marketed as Aranesp) to treat patients with anemia due to myelosuppressive chemotherapy.

The FDA said the REMS is no longer necessary to ensure that the benefits of Epogen/Procrit and Aranesp outweigh the risks these drugs pose, which include shortened overall survival and an increased risk of tumor progression or recurrence in patients with cancer.

The FDA has released the REMS requirements for these ESAs and said the risks the drugs pose can be communicated by the current product prescribing information.

The FDA decided the REMS is no longer needed based on its own analyses and an evaluation of the REMS assessment submitted by Amgen, Inc., the company that markets Epogen/Procrit and Aranesp.

Details on the analyses and evaluation are available from the following page on the FDA website: Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp).

Vials and a syringe

A new study suggests that having sickle cell disease (SCD) should not prevent patients from receiving tissue plasminogen activator (tPA) to treat ischemic stroke if they otherwise qualify for the treatment.

Researchers compared outcomes of tPA treatment in stroke patients with and without SCD and found no significant differences between the groups with regard to serious complications, length of hospital stay, or in-hospital mortality.

“Having sickle cell disease did not adversely affect any of the indicators we measured,” said Robert J. Adams, MD, of the Medical University of South Carolina in Charleston.

The SCD patients did have a higher rate of intracranial hemorrhage (ICH) than patients without SCD, although the rate was not significantly higher. Still, the researchers said further study is needed to look more closely at this outcome.

Dr Adams and his colleagues reported their findings in the journal Stroke.

The team noted that use of tPA has never been contraindicated in SCD, but guidelines recommend acute exchange transfusion for stroke in SCD, rather than tPA.

To gain more insight into the effects of tPA in patients with SCD, the researchers analyzed in-hospital data compiled by the quality improvement program Get With The Guidelines – Stroke.

The data included 2,016,652 stroke patients seen at 1952 participating US hospitals between January 2008 and March 2015. From these patients, the researchers identified 832 with SCD and 3328 age-, sex-, and race-matched controls.

There was no significant difference between the 2 cohorts in the rate of tPA use—8.2% for SCD patients and 9.4% for controls (P=0.3024).

Likewise, there was no significant difference in the timeliness of tPA administration. The median door-to-needle time was 73 minutes for SCD patients and 79 minutes for controls (P=0.3891).

Among patients who received tPA, there was no significant difference in the overall rate of serious complications, which occurred in 6.6% of the SCD patients and 6.0% of controls (P=0.7732).

Serious complications included symptomatic ICH, which occurred in 4.9% of the SCD patients and 3.2% of controls who received tPA (P= 0.4502).

Although this difference was not significant, the researchers said additional studies are needed to track the ICH rate in SCD patients receiving tPA.

The researchers also calculated the odds ratios (ORs) for various outcomes in tPA-treated SCD patients compared to controls.

In an analysis adjusted for multiple covariates, the OR for in-hospital mortality was 1.21 for SCD patients (P=0.4150), the OR for being discharged home was 0.90 (P=0.2686), and the OR for having a hospital stay lasting beyond 4 days was 1.15 (P=0.1151).

“People with sickle cell disease and an acute stroke who would otherwise qualify for tPA did not have worse outcomes than stroke patients who did not have sickle cell disease,” Dr Adams noted.

He and his colleagues said these findings suggest tPA is safe for patients with SCD and could potentially be used as a complementary therapy to red blood cell exchange, the current guideline-recommended frontline therapy for ischemic stroke in patients with SCD.

“These findings suggest that a future randomized trial that compares using red blood cell exchange alone versus combination therapy with tPA and red blood cell exchange should be undertaken to evaluate the outcomes of [ischemic stroke] in patients with sickle cell disease,” said study author Julie Kanter, MD, of the Medical University of South Carolina in Charleston.

Vials and a syringe

A new study suggests that having sickle cell disease (SCD) should not prevent patients from receiving tissue plasminogen activator (tPA) to treat ischemic stroke if they otherwise qualify for the treatment.

Researchers compared outcomes of tPA treatment in stroke patients with and without SCD and found no significant differences between the groups with regard to serious complications, length of hospital stay, or in-hospital mortality.

“Having sickle cell disease did not adversely affect any of the indicators we measured,” said Robert J. Adams, MD, of the Medical University of South Carolina in Charleston.

The SCD patients did have a higher rate of intracranial hemorrhage (ICH) than patients without SCD, although the rate was not significantly higher. Still, the researchers said further study is needed to look more closely at this outcome.

Dr Adams and his colleagues reported their findings in the journal Stroke.

The team noted that use of tPA has never been contraindicated in SCD, but guidelines recommend acute exchange transfusion for stroke in SCD, rather than tPA.

To gain more insight into the effects of tPA in patients with SCD, the researchers analyzed in-hospital data compiled by the quality improvement program Get With The Guidelines – Stroke.

The data included 2,016,652 stroke patients seen at 1952 participating US hospitals between January 2008 and March 2015. From these patients, the researchers identified 832 with SCD and 3328 age-, sex-, and race-matched controls.

There was no significant difference between the 2 cohorts in the rate of tPA use—8.2% for SCD patients and 9.4% for controls (P=0.3024).

Likewise, there was no significant difference in the timeliness of tPA administration. The median door-to-needle time was 73 minutes for SCD patients and 79 minutes for controls (P=0.3891).

Among patients who received tPA, there was no significant difference in the overall rate of serious complications, which occurred in 6.6% of the SCD patients and 6.0% of controls (P=0.7732).

Serious complications included symptomatic ICH, which occurred in 4.9% of the SCD patients and 3.2% of controls who received tPA (P= 0.4502).

Although this difference was not significant, the researchers said additional studies are needed to track the ICH rate in SCD patients receiving tPA.

The researchers also calculated the odds ratios (ORs) for various outcomes in tPA-treated SCD patients compared to controls.

In an analysis adjusted for multiple covariates, the OR for in-hospital mortality was 1.21 for SCD patients (P=0.4150), the OR for being discharged home was 0.90 (P=0.2686), and the OR for having a hospital stay lasting beyond 4 days was 1.15 (P=0.1151).

“People with sickle cell disease and an acute stroke who would otherwise qualify for tPA did not have worse outcomes than stroke patients who did not have sickle cell disease,” Dr Adams noted.

He and his colleagues said these findings suggest tPA is safe for patients with SCD and could potentially be used as a complementary therapy to red blood cell exchange, the current guideline-recommended frontline therapy for ischemic stroke in patients with SCD.

“These findings suggest that a future randomized trial that compares using red blood cell exchange alone versus combination therapy with tPA and red blood cell exchange should be undertaken to evaluate the outcomes of [ischemic stroke] in patients with sickle cell disease,” said study author Julie Kanter, MD, of the Medical University of South Carolina in Charleston.

Vials and a syringe

A new study suggests that having sickle cell disease (SCD) should not prevent patients from receiving tissue plasminogen activator (tPA) to treat ischemic stroke if they otherwise qualify for the treatment.

Researchers compared outcomes of tPA treatment in stroke patients with and without SCD and found no significant differences between the groups with regard to serious complications, length of hospital stay, or in-hospital mortality.

“Having sickle cell disease did not adversely affect any of the indicators we measured,” said Robert J. Adams, MD, of the Medical University of South Carolina in Charleston.

The SCD patients did have a higher rate of intracranial hemorrhage (ICH) than patients without SCD, although the rate was not significantly higher. Still, the researchers said further study is needed to look more closely at this outcome.

Dr Adams and his colleagues reported their findings in the journal Stroke.

The team noted that use of tPA has never been contraindicated in SCD, but guidelines recommend acute exchange transfusion for stroke in SCD, rather than tPA.

To gain more insight into the effects of tPA in patients with SCD, the researchers analyzed in-hospital data compiled by the quality improvement program Get With The Guidelines – Stroke.

The data included 2,016,652 stroke patients seen at 1952 participating US hospitals between January 2008 and March 2015. From these patients, the researchers identified 832 with SCD and 3328 age-, sex-, and race-matched controls.

There was no significant difference between the 2 cohorts in the rate of tPA use—8.2% for SCD patients and 9.4% for controls (P=0.3024).

Likewise, there was no significant difference in the timeliness of tPA administration. The median door-to-needle time was 73 minutes for SCD patients and 79 minutes for controls (P=0.3891).

Among patients who received tPA, there was no significant difference in the overall rate of serious complications, which occurred in 6.6% of the SCD patients and 6.0% of controls (P=0.7732).

Serious complications included symptomatic ICH, which occurred in 4.9% of the SCD patients and 3.2% of controls who received tPA (P= 0.4502).

Although this difference was not significant, the researchers said additional studies are needed to track the ICH rate in SCD patients receiving tPA.

The researchers also calculated the odds ratios (ORs) for various outcomes in tPA-treated SCD patients compared to controls.

In an analysis adjusted for multiple covariates, the OR for in-hospital mortality was 1.21 for SCD patients (P=0.4150), the OR for being discharged home was 0.90 (P=0.2686), and the OR for having a hospital stay lasting beyond 4 days was 1.15 (P=0.1151).

“People with sickle cell disease and an acute stroke who would otherwise qualify for tPA did not have worse outcomes than stroke patients who did not have sickle cell disease,” Dr Adams noted.

He and his colleagues said these findings suggest tPA is safe for patients with SCD and could potentially be used as a complementary therapy to red blood cell exchange, the current guideline-recommended frontline therapy for ischemic stroke in patients with SCD.

“These findings suggest that a future randomized trial that compares using red blood cell exchange alone versus combination therapy with tPA and red blood cell exchange should be undertaken to evaluate the outcomes of [ischemic stroke] in patients with sickle cell disease,” said study author Julie Kanter, MD, of the Medical University of South Carolina in Charleston.

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has authorized marketing of 23andMe Personal Genome Service (PGS) Genetic Health Risk (GHR) tests for 10 medical conditions.

These are the first direct-to-consumer tests authorized by the FDA that provide information on an individual’s genetic predisposition to certain conditions, including factor XI deficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary hemochromatosis, hereditary thrombophilia, and other conditions.

The GHR tests work by isolating DNA from a saliva sample, which is then tested for more than 500,000 genetic variants.

Consumers receive reports of the results, which tell them if they have an increased risk of developing any of the following 10 conditions.

Factor XI deficiency

The 23andMe PGS Genetic Health Risk Report for Factor XI Deficiency is indicated for reporting of the F283L, E117X, and IVS14+1G>A variants in the F11 gene.

This report describes if a person has a variant associated with factor XI deficiency and the potential for a higher risk of excessive bleeding following trauma or surgery, but it does not describe a person’s overall risk for excessive bleeding. This report is most relevant for people of Ashkenazi Jewish descent.

G6PD deficiency

The 23andMe PGS Genetic Health Risk Report for Glucose-6-Phosphate-Dehydrogenase Deficiency is indicated for reporting of the Val68Met variant in the G6PD gene.

This report describes if a person has a variant associated with G6PD deficiency and a higher risk for episodes of anemia, but it does not describe a person’s overall risk of developing anemia. This report is most relevant for people of African descent.

Hereditary hemochromatosis

The 23andMe PGS Genetic Health Risk Report for Hereditary Hemochromatosis is indicated for reporting of the C282Y and H63D variants in the HFE gene.

This report describes if a person has variants associated with hereditary hemochromatosis and a higher risk for iron overload, but it does not describe a person’s overall risk of developing iron overload. This report is most relevant for people of European descent.

Hereditary thrombophilia

The 23andMe PGS Genetic Health Risk Report for Hereditary Thrombophilia is indicated for reporting of the factor V Leiden variant in the F5 gene, as well as the prothrombin G20210A variant in the F2 gene.

This report describes if a person has variants associated with a higher risk of thrombosis, but it does not describe a person’s overall risk of developing thrombosis. This report is most relevant for people of European descent.

Alpha-1 antitrypsin deficiency (AATD)

The 23andMe PGS Genetic Health Risk Report for Alpha-I Antitrypsin Deficiency is indicated for reporting of the PI*Z and PI*S variants in the SERPINA1 gene.

This report describes if a person has variants associated with AATD and a higher risk for lung or liver disease, but it does not describe a person’s overall risk of developing lung or liver disease. This report is most relevant for people of European descent.

Celiac disease

The 23andMe PGS Genetic Health Risk Report for Celiac Disease is indicated for reporting of a variant in the HLA-DQ2.5 haplotype.

The report describes if a person has a haplotype associated with an increased risk of developing celiac disease, but it does not describe a person’s overall risk for developing celiac disease. This report is most relevant for people of European descent.

Early onset primary dystonia (DYT1/TOR1A-related)

The 23andMe PGS Genetic Health Risk Report for Early-Onset Primary Dystonia (DYT1/TOR1A-Related) is indicated for reporting of the deltaE302/303 variant in the DYT1 gene.

This report describes if a person has variants associated with a higher risk for early-onset primary dystonia, but it does not describe a person’s overall risk of developing dystonia. This report is most relevant for people of Ashkenazi Jewish descent.

 

Gaucher disease

The 23andMe PGS Genetic Health Risk Report for Gaucher Disease Type 1 is indicated for reporting of the N370S, 84GG, and V394L variants in the GBA gene.

This report describes if a person has variants associated with an increased risk for developing carrier status for Gaucher disease type 1 in adults. This report also describes if a result is associated with personal risk for developing symptoms of Gaucher disease type 1, but it does not describe a person’s overall risk of developing Gaucher disease type 1.

This test is most relevant for people of Ashkenazi Jewish descent.

Late-onset Alzheimer’s disease

The 23andMe PGS Genetic Health Risk Report for Late-onset Alzheimer’s Disease is indicated for reporting of the ε4 variant in the APOE gene.

The report describes if a person’s genetic result is associated with an increased risk of developing late-onset Alzheimer’s disease, but it does not describe a person’s overall risk of developing Alzheimer’s disease.

The ε4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent.

Parkinson’s disease

The 23andMe PGS Genetic Health Risk Report for Parkinson’s Disease is indicated for reporting of the G2019S variant in the LRRK2 gene and the N370S variant in the GBA gene.

The report describes if a person’s genetic result is associated with an increased risk of developing Parkinson’s disease, but it does not describe a person’s overall risk of developing Parkinson’s disease. The test is most relevant for people of European, Ashkenazi Jewish, and North African Berber descent.

Access to testing

23andMe, Inc. said it will release its first set of GHR tests—for hereditary thrombophilia, late-onset Alzheimer’s disease, Parkinson’s disease, alpha-1 antitrypsin deficiency, and Gaucher disease—this month. The remaining tests will follow.

New 23andMe Health + Ancestry Service customers in the US will have access to these tests. Current 23andMe customers will be notified directly regarding their eligibility.

About the marketing authorization

The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.

Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability, and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests.

The FDA intends to exempt additional 23andMe GHR tests from premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible after a one-time FDA review.

Excluded from the current marketing authorization and any future, related exemption are GHR tests that function as diagnostic tests.

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has authorized marketing of 23andMe Personal Genome Service (PGS) Genetic Health Risk (GHR) tests for 10 medical conditions.

These are the first direct-to-consumer tests authorized by the FDA that provide information on an individual’s genetic predisposition to certain conditions, including factor XI deficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary hemochromatosis, hereditary thrombophilia, and other conditions.

The GHR tests work by isolating DNA from a saliva sample, which is then tested for more than 500,000 genetic variants.

Consumers receive reports of the results, which tell them if they have an increased risk of developing any of the following 10 conditions.

Factor XI deficiency

The 23andMe PGS Genetic Health Risk Report for Factor XI Deficiency is indicated for reporting of the F283L, E117X, and IVS14+1G>A variants in the F11 gene.

This report describes if a person has a variant associated with factor XI deficiency and the potential for a higher risk of excessive bleeding following trauma or surgery, but it does not describe a person’s overall risk for excessive bleeding. This report is most relevant for people of Ashkenazi Jewish descent.

G6PD deficiency

The 23andMe PGS Genetic Health Risk Report for Glucose-6-Phosphate-Dehydrogenase Deficiency is indicated for reporting of the Val68Met variant in the G6PD gene.

This report describes if a person has a variant associated with G6PD deficiency and a higher risk for episodes of anemia, but it does not describe a person’s overall risk of developing anemia. This report is most relevant for people of African descent.

Hereditary hemochromatosis

The 23andMe PGS Genetic Health Risk Report for Hereditary Hemochromatosis is indicated for reporting of the C282Y and H63D variants in the HFE gene.

This report describes if a person has variants associated with hereditary hemochromatosis and a higher risk for iron overload, but it does not describe a person’s overall risk of developing iron overload. This report is most relevant for people of European descent.

Hereditary thrombophilia

The 23andMe PGS Genetic Health Risk Report for Hereditary Thrombophilia is indicated for reporting of the factor V Leiden variant in the F5 gene, as well as the prothrombin G20210A variant in the F2 gene.

This report describes if a person has variants associated with a higher risk of thrombosis, but it does not describe a person’s overall risk of developing thrombosis. This report is most relevant for people of European descent.

Alpha-1 antitrypsin deficiency (AATD)

The 23andMe PGS Genetic Health Risk Report for Alpha-I Antitrypsin Deficiency is indicated for reporting of the PI*Z and PI*S variants in the SERPINA1 gene.

This report describes if a person has variants associated with AATD and a higher risk for lung or liver disease, but it does not describe a person’s overall risk of developing lung or liver disease. This report is most relevant for people of European descent.

Celiac disease

The 23andMe PGS Genetic Health Risk Report for Celiac Disease is indicated for reporting of a variant in the HLA-DQ2.5 haplotype.

The report describes if a person has a haplotype associated with an increased risk of developing celiac disease, but it does not describe a person’s overall risk for developing celiac disease. This report is most relevant for people of European descent.

Early onset primary dystonia (DYT1/TOR1A-related)

The 23andMe PGS Genetic Health Risk Report for Early-Onset Primary Dystonia (DYT1/TOR1A-Related) is indicated for reporting of the deltaE302/303 variant in the DYT1 gene.

This report describes if a person has variants associated with a higher risk for early-onset primary dystonia, but it does not describe a person’s overall risk of developing dystonia. This report is most relevant for people of Ashkenazi Jewish descent.

 

Gaucher disease

The 23andMe PGS Genetic Health Risk Report for Gaucher Disease Type 1 is indicated for reporting of the N370S, 84GG, and V394L variants in the GBA gene.

This report describes if a person has variants associated with an increased risk for developing carrier status for Gaucher disease type 1 in adults. This report also describes if a result is associated with personal risk for developing symptoms of Gaucher disease type 1, but it does not describe a person’s overall risk of developing Gaucher disease type 1.

This test is most relevant for people of Ashkenazi Jewish descent.

Late-onset Alzheimer’s disease

The 23andMe PGS Genetic Health Risk Report for Late-onset Alzheimer’s Disease is indicated for reporting of the ε4 variant in the APOE gene.

The report describes if a person’s genetic result is associated with an increased risk of developing late-onset Alzheimer’s disease, but it does not describe a person’s overall risk of developing Alzheimer’s disease.

The ε4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent.

Parkinson’s disease

The 23andMe PGS Genetic Health Risk Report for Parkinson’s Disease is indicated for reporting of the G2019S variant in the LRRK2 gene and the N370S variant in the GBA gene.

The report describes if a person’s genetic result is associated with an increased risk of developing Parkinson’s disease, but it does not describe a person’s overall risk of developing Parkinson’s disease. The test is most relevant for people of European, Ashkenazi Jewish, and North African Berber descent.

Access to testing

23andMe, Inc. said it will release its first set of GHR tests—for hereditary thrombophilia, late-onset Alzheimer’s disease, Parkinson’s disease, alpha-1 antitrypsin deficiency, and Gaucher disease—this month. The remaining tests will follow.

New 23andMe Health + Ancestry Service customers in the US will have access to these tests. Current 23andMe customers will be notified directly regarding their eligibility.

About the marketing authorization

The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.

Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability, and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests.

The FDA intends to exempt additional 23andMe GHR tests from premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible after a one-time FDA review.

Excluded from the current marketing authorization and any future, related exemption are GHR tests that function as diagnostic tests.

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has authorized marketing of 23andMe Personal Genome Service (PGS) Genetic Health Risk (GHR) tests for 10 medical conditions.

These are the first direct-to-consumer tests authorized by the FDA that provide information on an individual’s genetic predisposition to certain conditions, including factor XI deficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary hemochromatosis, hereditary thrombophilia, and other conditions.

The GHR tests work by isolating DNA from a saliva sample, which is then tested for more than 500,000 genetic variants.

Consumers receive reports of the results, which tell them if they have an increased risk of developing any of the following 10 conditions.

Factor XI deficiency

The 23andMe PGS Genetic Health Risk Report for Factor XI Deficiency is indicated for reporting of the F283L, E117X, and IVS14+1G>A variants in the F11 gene.

This report describes if a person has a variant associated with factor XI deficiency and the potential for a higher risk of excessive bleeding following trauma or surgery, but it does not describe a person’s overall risk for excessive bleeding. This report is most relevant for people of Ashkenazi Jewish descent.

G6PD deficiency

The 23andMe PGS Genetic Health Risk Report for Glucose-6-Phosphate-Dehydrogenase Deficiency is indicated for reporting of the Val68Met variant in the G6PD gene.

This report describes if a person has a variant associated with G6PD deficiency and a higher risk for episodes of anemia, but it does not describe a person’s overall risk of developing anemia. This report is most relevant for people of African descent.

Hereditary hemochromatosis

The 23andMe PGS Genetic Health Risk Report for Hereditary Hemochromatosis is indicated for reporting of the C282Y and H63D variants in the HFE gene.

This report describes if a person has variants associated with hereditary hemochromatosis and a higher risk for iron overload, but it does not describe a person’s overall risk of developing iron overload. This report is most relevant for people of European descent.

Hereditary thrombophilia

The 23andMe PGS Genetic Health Risk Report for Hereditary Thrombophilia is indicated for reporting of the factor V Leiden variant in the F5 gene, as well as the prothrombin G20210A variant in the F2 gene.

This report describes if a person has variants associated with a higher risk of thrombosis, but it does not describe a person’s overall risk of developing thrombosis. This report is most relevant for people of European descent.

Alpha-1 antitrypsin deficiency (AATD)

The 23andMe PGS Genetic Health Risk Report for Alpha-I Antitrypsin Deficiency is indicated for reporting of the PI*Z and PI*S variants in the SERPINA1 gene.

This report describes if a person has variants associated with AATD and a higher risk for lung or liver disease, but it does not describe a person’s overall risk of developing lung or liver disease. This report is most relevant for people of European descent.

Celiac disease

The 23andMe PGS Genetic Health Risk Report for Celiac Disease is indicated for reporting of a variant in the HLA-DQ2.5 haplotype.

The report describes if a person has a haplotype associated with an increased risk of developing celiac disease, but it does not describe a person’s overall risk for developing celiac disease. This report is most relevant for people of European descent.

Early onset primary dystonia (DYT1/TOR1A-related)

The 23andMe PGS Genetic Health Risk Report for Early-Onset Primary Dystonia (DYT1/TOR1A-Related) is indicated for reporting of the deltaE302/303 variant in the DYT1 gene.

This report describes if a person has variants associated with a higher risk for early-onset primary dystonia, but it does not describe a person’s overall risk of developing dystonia. This report is most relevant for people of Ashkenazi Jewish descent.

 

Gaucher disease

The 23andMe PGS Genetic Health Risk Report for Gaucher Disease Type 1 is indicated for reporting of the N370S, 84GG, and V394L variants in the GBA gene.

This report describes if a person has variants associated with an increased risk for developing carrier status for Gaucher disease type 1 in adults. This report also describes if a result is associated with personal risk for developing symptoms of Gaucher disease type 1, but it does not describe a person’s overall risk of developing Gaucher disease type 1.

This test is most relevant for people of Ashkenazi Jewish descent.

Late-onset Alzheimer’s disease

The 23andMe PGS Genetic Health Risk Report for Late-onset Alzheimer’s Disease is indicated for reporting of the ε4 variant in the APOE gene.

The report describes if a person’s genetic result is associated with an increased risk of developing late-onset Alzheimer’s disease, but it does not describe a person’s overall risk of developing Alzheimer’s disease.

The ε4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent.

Parkinson’s disease

The 23andMe PGS Genetic Health Risk Report for Parkinson’s Disease is indicated for reporting of the G2019S variant in the LRRK2 gene and the N370S variant in the GBA gene.

The report describes if a person’s genetic result is associated with an increased risk of developing Parkinson’s disease, but it does not describe a person’s overall risk of developing Parkinson’s disease. The test is most relevant for people of European, Ashkenazi Jewish, and North African Berber descent.

Access to testing

23andMe, Inc. said it will release its first set of GHR tests—for hereditary thrombophilia, late-onset Alzheimer’s disease, Parkinson’s disease, alpha-1 antitrypsin deficiency, and Gaucher disease—this month. The remaining tests will follow.

New 23andMe Health + Ancestry Service customers in the US will have access to these tests. Current 23andMe customers will be notified directly regarding their eligibility.

About the marketing authorization

The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.

Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability, and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests.

The FDA intends to exempt additional 23andMe GHR tests from premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible after a one-time FDA review.

Excluded from the current marketing authorization and any future, related exemption are GHR tests that function as diagnostic tests.

Red blood cells

The US Food and Drug Administration (FDA) has granted fast track designation to Coversin™ for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms conferring eculizumab resistance.

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9, and also independently inhibits LTB4 activity.

Coversin is being developed by Akari Therapeutics.

Akari is evaluating Coversin in a pair of phase 2 trials.

In the first trial, researchers are evaluating Coversin in patients with PNH who have never received a complement-blocking therapy. Interim results from this ongoing trial are scheduled to be presented at Akari’s Research and Development Day on April 24 in New York, New York.

In the second phase 2 trial, researchers are evaluating Coversin in patients with PNH who have C5 polymorphisms that confer resistance to eculizumab.

One patient has been enrolled in this trial and has received Coversin for over a year. The treatment has resulted in significant lactate dehydrogenase reduction and complete complement blockade.

About fast track designation

The FDA created the fast track program to facilitate the development and expedite the review of drugs that show promise for treating serious or life-threatening diseases and address unmet medical needs.

Companies developing drugs that receive fast track designation benefit from more frequent communications and meetings with the FDA to review their drug’s development plan, including the design of proposed clinical trials, use of biomarkers, and the extent of data needed for approval.

Drugs with fast track designation may qualify for priority review as well, if relevant criteria are met. Priority review shortens the FDA review process from 10 months to 6 months.

Fast track designation also allows for a rolling review process, whereby completed sections of the investigational new drug application can be submitted for FDA review as they become available, instead of waiting for all sections to be completed.

Red blood cells

The US Food and Drug Administration (FDA) has granted fast track designation to Coversin™ for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms conferring eculizumab resistance.

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9, and also independently inhibits LTB4 activity.

Coversin is being developed by Akari Therapeutics.

Akari is evaluating Coversin in a pair of phase 2 trials.

In the first trial, researchers are evaluating Coversin in patients with PNH who have never received a complement-blocking therapy. Interim results from this ongoing trial are scheduled to be presented at Akari’s Research and Development Day on April 24 in New York, New York.

In the second phase 2 trial, researchers are evaluating Coversin in patients with PNH who have C5 polymorphisms that confer resistance to eculizumab.

One patient has been enrolled in this trial and has received Coversin for over a year. The treatment has resulted in significant lactate dehydrogenase reduction and complete complement blockade.

About fast track designation

The FDA created the fast track program to facilitate the development and expedite the review of drugs that show promise for treating serious or life-threatening diseases and address unmet medical needs.

Companies developing drugs that receive fast track designation benefit from more frequent communications and meetings with the FDA to review their drug’s development plan, including the design of proposed clinical trials, use of biomarkers, and the extent of data needed for approval.

Drugs with fast track designation may qualify for priority review as well, if relevant criteria are met. Priority review shortens the FDA review process from 10 months to 6 months.

Fast track designation also allows for a rolling review process, whereby completed sections of the investigational new drug application can be submitted for FDA review as they become available, instead of waiting for all sections to be completed.

Red blood cells

The US Food and Drug Administration (FDA) has granted fast track designation to Coversin™ for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients who have polymorphisms conferring eculizumab resistance.

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9, and also independently inhibits LTB4 activity.

Coversin is being developed by Akari Therapeutics.

Akari is evaluating Coversin in a pair of phase 2 trials.

In the first trial, researchers are evaluating Coversin in patients with PNH who have never received a complement-blocking therapy. Interim results from this ongoing trial are scheduled to be presented at Akari’s Research and Development Day on April 24 in New York, New York.

In the second phase 2 trial, researchers are evaluating Coversin in patients with PNH who have C5 polymorphisms that confer resistance to eculizumab.

One patient has been enrolled in this trial and has received Coversin for over a year. The treatment has resulted in significant lactate dehydrogenase reduction and complete complement blockade.

About fast track designation

The FDA created the fast track program to facilitate the development and expedite the review of drugs that show promise for treating serious or life-threatening diseases and address unmet medical needs.

Companies developing drugs that receive fast track designation benefit from more frequent communications and meetings with the FDA to review their drug’s development plan, including the design of proposed clinical trials, use of biomarkers, and the extent of data needed for approval.

Drugs with fast track designation may qualify for priority review as well, if relevant criteria are met. Priority review shortens the FDA review process from 10 months to 6 months.

Fast track designation also allows for a rolling review process, whereby completed sections of the investigational new drug application can be submitted for FDA review as they become available, instead of waiting for all sections to be completed.

Photo by Chad McNeeley

MARSEILLE—An investigational drug has successfully treated a severe case of transplant-associated thrombotic microangiopathy (TA-TMA), according to a presentation at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation.

The drug is OMS721, a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.

The patient received OMS721, which is being developed by Omeros Corporation, under a compassionate-use protocol.

Marco Zecca, MD, of the Fondazione IRCCS Policlinico San Matteo in Italy, and his colleagues provided details on this patient in a poster presented at the meeting (Physician Poster Abstracts-Day 1, abstract A437).

The female patient had undergone a hematopoietic stem cell transplant to treat Diamond‐Blackfan anemia. At age 14, she received a transplant from an HLA-compatible, unrelated donor.

Seven months later, she was diagnosed with TA-TMA. The patient was initially treated with eculizumab but had to stop taking the drug after she developed acute pulmonary edema.

She was then treated with plasma exchange but experienced a TA-TMA relapse at 11 months. The patient was again treated with eculizumab and again had to discontinue the drug after developing acute pulmonary edema.

The patient’s condition continued to worsen, and she soon required hemodialysis 3 times a week as well as daily platelet transfusions.

Dr Zecca requested OMS721 as compassionate-use treatment for the patient, and Omeros complied.

Two months after starting OMS721, the patient was able to discontinue hemodialysis and decrease her platelet transfusion requirements. She did not experience any adverse events related to OMS721.

Recently, the patient’s dose was tapered, but she developed a viral infection that reactivated her TA-TMA.

A return to the original dose of OMS721 was successful. Now, the patient no longer requires dialysis or transfusions.

“This patient had severe TMA that I believe would have caused her death,” Dr Zecca said. “Her positive response to OMS721 treatment, both initially and following her virus-induced relapse during tapering, was impressive.”

“The results of OMS721 treatment in this challenge-rechallenge scenario underscore the important effects of the drug. Since the poster was produced, her TMA has remained in remission, and we have been able to discontinue her platelet transfusions. Her rapid response has been heartening, and we all are grateful for this remarkable outcome.”

Photo by Chad McNeeley

MARSEILLE—An investigational drug has successfully treated a severe case of transplant-associated thrombotic microangiopathy (TA-TMA), according to a presentation at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation.

The drug is OMS721, a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.

The patient received OMS721, which is being developed by Omeros Corporation, under a compassionate-use protocol.

Marco Zecca, MD, of the Fondazione IRCCS Policlinico San Matteo in Italy, and his colleagues provided details on this patient in a poster presented at the meeting (Physician Poster Abstracts-Day 1, abstract A437).

The female patient had undergone a hematopoietic stem cell transplant to treat Diamond‐Blackfan anemia. At age 14, she received a transplant from an HLA-compatible, unrelated donor.

Seven months later, she was diagnosed with TA-TMA. The patient was initially treated with eculizumab but had to stop taking the drug after she developed acute pulmonary edema.

She was then treated with plasma exchange but experienced a TA-TMA relapse at 11 months. The patient was again treated with eculizumab and again had to discontinue the drug after developing acute pulmonary edema.

The patient’s condition continued to worsen, and she soon required hemodialysis 3 times a week as well as daily platelet transfusions.

Dr Zecca requested OMS721 as compassionate-use treatment for the patient, and Omeros complied.

Two months after starting OMS721, the patient was able to discontinue hemodialysis and decrease her platelet transfusion requirements. She did not experience any adverse events related to OMS721.

Recently, the patient’s dose was tapered, but she developed a viral infection that reactivated her TA-TMA.

A return to the original dose of OMS721 was successful. Now, the patient no longer requires dialysis or transfusions.

“This patient had severe TMA that I believe would have caused her death,” Dr Zecca said. “Her positive response to OMS721 treatment, both initially and following her virus-induced relapse during tapering, was impressive.”

“The results of OMS721 treatment in this challenge-rechallenge scenario underscore the important effects of the drug. Since the poster was produced, her TMA has remained in remission, and we have been able to discontinue her platelet transfusions. Her rapid response has been heartening, and we all are grateful for this remarkable outcome.”

Photo by Chad McNeeley

MARSEILLE—An investigational drug has successfully treated a severe case of transplant-associated thrombotic microangiopathy (TA-TMA), according to a presentation at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation.

The drug is OMS721, a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.

The patient received OMS721, which is being developed by Omeros Corporation, under a compassionate-use protocol.

Marco Zecca, MD, of the Fondazione IRCCS Policlinico San Matteo in Italy, and his colleagues provided details on this patient in a poster presented at the meeting (Physician Poster Abstracts-Day 1, abstract A437).

The female patient had undergone a hematopoietic stem cell transplant to treat Diamond‐Blackfan anemia. At age 14, she received a transplant from an HLA-compatible, unrelated donor.

Seven months later, she was diagnosed with TA-TMA. The patient was initially treated with eculizumab but had to stop taking the drug after she developed acute pulmonary edema.

She was then treated with plasma exchange but experienced a TA-TMA relapse at 11 months. The patient was again treated with eculizumab and again had to discontinue the drug after developing acute pulmonary edema.

The patient’s condition continued to worsen, and she soon required hemodialysis 3 times a week as well as daily platelet transfusions.

Dr Zecca requested OMS721 as compassionate-use treatment for the patient, and Omeros complied.

Two months after starting OMS721, the patient was able to discontinue hemodialysis and decrease her platelet transfusion requirements. She did not experience any adverse events related to OMS721.

Recently, the patient’s dose was tapered, but she developed a viral infection that reactivated her TA-TMA.

A return to the original dose of OMS721 was successful. Now, the patient no longer requires dialysis or transfusions.

“This patient had severe TMA that I believe would have caused her death,” Dr Zecca said. “Her positive response to OMS721 treatment, both initially and following her virus-induced relapse during tapering, was impressive.”

“The results of OMS721 treatment in this challenge-rechallenge scenario underscore the important effects of the drug. Since the poster was produced, her TMA has remained in remission, and we have been able to discontinue her platelet transfusions. Her rapid response has been heartening, and we all are grateful for this remarkable outcome.”

Micrograph showing MDS

The protein p300 may prevent the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), according to research published in Leukemia.

Researchers found that loss of p300 “markedly” increased leukemogenesis in a mouse model of MDS.

“The loss of p300 allows these defective [MDS] cells to grow and become leukemic,” said study author Stephen Nimer, MD, of Sylvester Comprehensive Cancer Center in Miami, Florida.

“This work offers us a window into AML, which we are now going to try to exploit.”

Previous research suggested that p300 and CBP (both histone lysine acetyltransferases) may be tumor suppressors. The current study indicates that, in the context of MDS, that is only true for p300.

The researchers evaluated the effects of deleting both p300 and CBP in Nup98-HoxD13 (NHD13) transgenic mice, a model of human MDS.

The team found that p300 deletion, but not CBP deletion, accelerated leukemogenesis in the mice.

“When we eliminated p300, 100% of the mice developed leukemia,” Dr Nimer said. “It indicated that, under this specific circumstance, p300 is a tumor suppressor, offering great insight into how MDS converts to leukemia. It was quite surprising that CBP plays no role at all.”

The researchers also found that deleting p300 restored the ability of NHD13-expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew, and p300 deletion decreased apoptosis.

“While investigating how p300 functions in MDS cells, we found that MDS cells do not grow well in the lab,” Dr Nimer said. “However, when you eliminate p300, suddenly, the cells continue to grow.”

On the other hand, deletion of p300 did not have a significant effect on wild-type hematopoiesis.

Finally, the researchers found that p300 deletion enhanced cytokine signaling in NHD13-expressing HSPCs. They observed enhanced activation of the MAPK and JAK/STAT pathways in HSPCs isolated from NHD13 transgenic mice.

The team said more research is needed to understand exactly how p300 controls MDS cells, but these findings could ultimately help MDS patients avoid AML.

“Other than chemotherapy, right now, there’s no way to prevent MDS from developing into myeloid leukemia,” Dr Nimer said. “However, drugs are being developed that can promote p300 function and possibly prevent MDS patients from developing leukemia.”

Micrograph showing MDS

The protein p300 may prevent the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), according to research published in Leukemia.

Researchers found that loss of p300 “markedly” increased leukemogenesis in a mouse model of MDS.

“The loss of p300 allows these defective [MDS] cells to grow and become leukemic,” said study author Stephen Nimer, MD, of Sylvester Comprehensive Cancer Center in Miami, Florida.

“This work offers us a window into AML, which we are now going to try to exploit.”

Previous research suggested that p300 and CBP (both histone lysine acetyltransferases) may be tumor suppressors. The current study indicates that, in the context of MDS, that is only true for p300.

The researchers evaluated the effects of deleting both p300 and CBP in Nup98-HoxD13 (NHD13) transgenic mice, a model of human MDS.

The team found that p300 deletion, but not CBP deletion, accelerated leukemogenesis in the mice.

“When we eliminated p300, 100% of the mice developed leukemia,” Dr Nimer said. “It indicated that, under this specific circumstance, p300 is a tumor suppressor, offering great insight into how MDS converts to leukemia. It was quite surprising that CBP plays no role at all.”

The researchers also found that deleting p300 restored the ability of NHD13-expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew, and p300 deletion decreased apoptosis.

“While investigating how p300 functions in MDS cells, we found that MDS cells do not grow well in the lab,” Dr Nimer said. “However, when you eliminate p300, suddenly, the cells continue to grow.”

On the other hand, deletion of p300 did not have a significant effect on wild-type hematopoiesis.

Finally, the researchers found that p300 deletion enhanced cytokine signaling in NHD13-expressing HSPCs. They observed enhanced activation of the MAPK and JAK/STAT pathways in HSPCs isolated from NHD13 transgenic mice.

The team said more research is needed to understand exactly how p300 controls MDS cells, but these findings could ultimately help MDS patients avoid AML.

“Other than chemotherapy, right now, there’s no way to prevent MDS from developing into myeloid leukemia,” Dr Nimer said. “However, drugs are being developed that can promote p300 function and possibly prevent MDS patients from developing leukemia.”

Micrograph showing MDS

The protein p300 may prevent the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), according to research published in Leukemia.

Researchers found that loss of p300 “markedly” increased leukemogenesis in a mouse model of MDS.

“The loss of p300 allows these defective [MDS] cells to grow and become leukemic,” said study author Stephen Nimer, MD, of Sylvester Comprehensive Cancer Center in Miami, Florida.

“This work offers us a window into AML, which we are now going to try to exploit.”

Previous research suggested that p300 and CBP (both histone lysine acetyltransferases) may be tumor suppressors. The current study indicates that, in the context of MDS, that is only true for p300.

The researchers evaluated the effects of deleting both p300 and CBP in Nup98-HoxD13 (NHD13) transgenic mice, a model of human MDS.

The team found that p300 deletion, but not CBP deletion, accelerated leukemogenesis in the mice.

“When we eliminated p300, 100% of the mice developed leukemia,” Dr Nimer said. “It indicated that, under this specific circumstance, p300 is a tumor suppressor, offering great insight into how MDS converts to leukemia. It was quite surprising that CBP plays no role at all.”

The researchers also found that deleting p300 restored the ability of NHD13-expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew, and p300 deletion decreased apoptosis.

“While investigating how p300 functions in MDS cells, we found that MDS cells do not grow well in the lab,” Dr Nimer said. “However, when you eliminate p300, suddenly, the cells continue to grow.”

On the other hand, deletion of p300 did not have a significant effect on wild-type hematopoiesis.

Finally, the researchers found that p300 deletion enhanced cytokine signaling in NHD13-expressing HSPCs. They observed enhanced activation of the MAPK and JAK/STAT pathways in HSPCs isolated from NHD13 transgenic mice.

The team said more research is needed to understand exactly how p300 controls MDS cells, but these findings could ultimately help MDS patients avoid AML.

“Other than chemotherapy, right now, there’s no way to prevent MDS from developing into myeloid leukemia,” Dr Nimer said. “However, drugs are being developed that can promote p300 function and possibly prevent MDS patients from developing leukemia.”

Lab mouse

The lungs may play a previously unrecognized role in blood production, according to preclinical research published in Nature.

Researchers discovered large numbers of megakaryocytes in the lungs of mice and found these cells produced roughly half of the animals’ platelets.

The team also identified a pool of hematopoietic progenitors in the extravascular spaces of mouse lungs that were capable of multi-lineage bone marrow reconstitution.

“This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said study author Mark R. Looney, MD, of the University of California - San Francisco.

“What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The researchers believe these findings could have major implications for understanding diseases in which patients suffer from thrombocytopenia.

Imaging reveals surprise

This research was made possible by a refinement of a technique known as 2-photon intravital imaging. This approach allowed the researchers to visualize the behavior of individual cells within the blood vessels of a living mouse lung.

Dr Looney and his colleagues used the technique to examine interactions between the immune system and circulating platelets in the lungs in a mouse strain engineered so that platelets emit bright green fluorescence (GFP+).

In this way, the team noticed a large population of megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said study author Emma Lefrançais, PhD, a postdoctoral researcher in Dr Looney’s lab.

More detailed imaging sessions revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature. This suggests that roughly half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.

Subsequent experiments also revealed a variety of previously overlooked hematopoietic progenitors outside the lung vasculature.

Transplants provide more insight

The discovery of megakaryocytes and hematopoietic progenitors in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a set of lung transplant studies.

The team transplanted lungs from wild-type mice into mice with GFP+ megakaryocytes and vice-versa. The researchers said they observed proplatelet formation from GFP+ megakaryocytes in the lung vasculature of the GFP+ mice but not in the wild-type mice.

This suggests the megakaryocytes releasing platelets in the lung circulation originate from outside the lungs, the researchers said. And subsequent experiments suggested the megakaryocytes originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, a postdoctoral researcher in Dr Looney’s lab.

“It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with GFP+ megakaryocyte progenitors into mutant mice with low platelet counts.

The transplants successfully restored platelet levels to normal, an effect that persisted over a few months of observation—much longer than the lifespan of individual megakaryocytes or platelets.

 

To the researchers, this indicated that resident megakaryocyte progenitors in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy megakaryocytes to restore proper platelet production.

Finally, the researchers tested whether lung hematopoietic progenitors were capable of multi-lineage bone marrow reconstitution.

They found that cells originating from transplanted lungs traveled to damaged bone marrow and contributed to the production of platelets and other blood cells, including neutrophils, B cells, and T cells.

The researchers said these experiments suggest the lungs play host to a variety of hematopoietic progenitors capable of reconstituting damaged bone marrow and restoring the production of many components of the blood.

“To our knowledge, this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Dr Looney said.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Dr Looney noted.

The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of this study for Nature.

“The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

Lab mouse

The lungs may play a previously unrecognized role in blood production, according to preclinical research published in Nature.

Researchers discovered large numbers of megakaryocytes in the lungs of mice and found these cells produced roughly half of the animals’ platelets.

The team also identified a pool of hematopoietic progenitors in the extravascular spaces of mouse lungs that were capable of multi-lineage bone marrow reconstitution.

“This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said study author Mark R. Looney, MD, of the University of California - San Francisco.

“What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The researchers believe these findings could have major implications for understanding diseases in which patients suffer from thrombocytopenia.

Imaging reveals surprise

This research was made possible by a refinement of a technique known as 2-photon intravital imaging. This approach allowed the researchers to visualize the behavior of individual cells within the blood vessels of a living mouse lung.

Dr Looney and his colleagues used the technique to examine interactions between the immune system and circulating platelets in the lungs in a mouse strain engineered so that platelets emit bright green fluorescence (GFP+).

In this way, the team noticed a large population of megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said study author Emma Lefrançais, PhD, a postdoctoral researcher in Dr Looney’s lab.

More detailed imaging sessions revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature. This suggests that roughly half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.

Subsequent experiments also revealed a variety of previously overlooked hematopoietic progenitors outside the lung vasculature.

Transplants provide more insight

The discovery of megakaryocytes and hematopoietic progenitors in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a set of lung transplant studies.

The team transplanted lungs from wild-type mice into mice with GFP+ megakaryocytes and vice-versa. The researchers said they observed proplatelet formation from GFP+ megakaryocytes in the lung vasculature of the GFP+ mice but not in the wild-type mice.

This suggests the megakaryocytes releasing platelets in the lung circulation originate from outside the lungs, the researchers said. And subsequent experiments suggested the megakaryocytes originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, a postdoctoral researcher in Dr Looney’s lab.

“It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with GFP+ megakaryocyte progenitors into mutant mice with low platelet counts.

The transplants successfully restored platelet levels to normal, an effect that persisted over a few months of observation—much longer than the lifespan of individual megakaryocytes or platelets.

 

To the researchers, this indicated that resident megakaryocyte progenitors in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy megakaryocytes to restore proper platelet production.

Finally, the researchers tested whether lung hematopoietic progenitors were capable of multi-lineage bone marrow reconstitution.

They found that cells originating from transplanted lungs traveled to damaged bone marrow and contributed to the production of platelets and other blood cells, including neutrophils, B cells, and T cells.

The researchers said these experiments suggest the lungs play host to a variety of hematopoietic progenitors capable of reconstituting damaged bone marrow and restoring the production of many components of the blood.

“To our knowledge, this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Dr Looney said.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Dr Looney noted.

The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of this study for Nature.

“The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

Lab mouse

The lungs may play a previously unrecognized role in blood production, according to preclinical research published in Nature.

Researchers discovered large numbers of megakaryocytes in the lungs of mice and found these cells produced roughly half of the animals’ platelets.

The team also identified a pool of hematopoietic progenitors in the extravascular spaces of mouse lungs that were capable of multi-lineage bone marrow reconstitution.

“This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said study author Mark R. Looney, MD, of the University of California - San Francisco.

“What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The researchers believe these findings could have major implications for understanding diseases in which patients suffer from thrombocytopenia.

Imaging reveals surprise

This research was made possible by a refinement of a technique known as 2-photon intravital imaging. This approach allowed the researchers to visualize the behavior of individual cells within the blood vessels of a living mouse lung.

Dr Looney and his colleagues used the technique to examine interactions between the immune system and circulating platelets in the lungs in a mouse strain engineered so that platelets emit bright green fluorescence (GFP+).

In this way, the team noticed a large population of megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said study author Emma Lefrançais, PhD, a postdoctoral researcher in Dr Looney’s lab.

More detailed imaging sessions revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature. This suggests that roughly half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.

Subsequent experiments also revealed a variety of previously overlooked hematopoietic progenitors outside the lung vasculature.

Transplants provide more insight

The discovery of megakaryocytes and hematopoietic progenitors in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a set of lung transplant studies.

The team transplanted lungs from wild-type mice into mice with GFP+ megakaryocytes and vice-versa. The researchers said they observed proplatelet formation from GFP+ megakaryocytes in the lung vasculature of the GFP+ mice but not in the wild-type mice.

This suggests the megakaryocytes releasing platelets in the lung circulation originate from outside the lungs, the researchers said. And subsequent experiments suggested the megakaryocytes originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, a postdoctoral researcher in Dr Looney’s lab.

“It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with GFP+ megakaryocyte progenitors into mutant mice with low platelet counts.

The transplants successfully restored platelet levels to normal, an effect that persisted over a few months of observation—much longer than the lifespan of individual megakaryocytes or platelets.

 

To the researchers, this indicated that resident megakaryocyte progenitors in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy megakaryocytes to restore proper platelet production.

Finally, the researchers tested whether lung hematopoietic progenitors were capable of multi-lineage bone marrow reconstitution.

They found that cells originating from transplanted lungs traveled to damaged bone marrow and contributed to the production of platelets and other blood cells, including neutrophils, B cells, and T cells.

The researchers said these experiments suggest the lungs play host to a variety of hematopoietic progenitors capable of reconstituting damaged bone marrow and restoring the production of many components of the blood.

“To our knowledge, this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Dr Looney said.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Dr Looney noted.

The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of this study for Nature.

“The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

Photo from David Levy

Physicians have reported what they believe is the first case of an allogeneic hematopoietic stem cell transplant (allo-HSCT) curing an adult with congenital dyserythropoietic anemia (CDA).

The patient, David Levy, was previously transfusion-dependent and suffered from iron overload, severe pain, and other adverse effects of his illness.

Levy was denied a transplant for years, but, in 2014, he received a non-myeloablative allo-HSCT from a matched, unrelated donor.

Now, Levy no longer requires transfusions, iron chelation, or immunosuppression, and says he is able to live a normal life.

Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues described Levy’s case in a letter to Bone Marrow Transplantation.

Levy was diagnosed with CDA at 4 months of age and was treated with regular blood transfusions for most of his life. He was 24 when the pain from his illness became so severe that he had to withdraw from graduate school.

“I spent the following years doing nothing—no work, no school, no social contact—because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every 2 to 3 weeks, had undergone a splenectomy, had an enlarged liver, and was suffering from fatigue, heart palpitations, and iron overload.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr Rondelli.”

Dr Rondelli said that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a transplant.

However, Dr Rondelli and his colleagues had reported success with chemotherapy-free allo-HSCT in patients with sickle cell disease. So Dr Rondelli performed Levy’s transplant in 2014.

Levy received a peripheral blood stem cell transplant from an unrelated donor who was a 10/10 HLA match but ABO incompatible. He received conditioning with rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.

Levy also received graft-vs-host disease (GVHD) prophylaxis consisting of high-dose cyclophosphamide, mycophenolate mofetil, and sirolimus. And he received standard antibacterial, antifungal, antiviral, and anti-Pneumocystis jiroveci prophylaxis.

Levy experienced platelet engraftment on day 20 and neutrophil engraftment on day 21. Whole-blood donor-cell chimerism was 98.7% on day 30 and 100% on day 60 and beyond.

Levy did develop transient hemolytic anemia due to the ABO incompatibility. He was given a total of 10 units of packed red blood cells until day 78.

Levy was tapered off all immunosuppression at 12 months and has shown no signs of acute or chronic GVHD.

At 24 months after HSCT, Levy’s hemoglobin was 13.7 g/dL, and his ferritin was 376 ng/mL. He has had no iron chelation since the transplant.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, who is now 35.

“I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Dr Rondelli said the potential of this treatment approach is promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias—perhaps the only possible cure,” he said.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant. This procedure gives some adults the option of a stem cell transplant, which was not previously available.”

Photo from David Levy

Physicians have reported what they believe is the first case of an allogeneic hematopoietic stem cell transplant (allo-HSCT) curing an adult with congenital dyserythropoietic anemia (CDA).

The patient, David Levy, was previously transfusion-dependent and suffered from iron overload, severe pain, and other adverse effects of his illness.

Levy was denied a transplant for years, but, in 2014, he received a non-myeloablative allo-HSCT from a matched, unrelated donor.

Now, Levy no longer requires transfusions, iron chelation, or immunosuppression, and says he is able to live a normal life.

Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues described Levy’s case in a letter to Bone Marrow Transplantation.

Levy was diagnosed with CDA at 4 months of age and was treated with regular blood transfusions for most of his life. He was 24 when the pain from his illness became so severe that he had to withdraw from graduate school.

“I spent the following years doing nothing—no work, no school, no social contact—because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every 2 to 3 weeks, had undergone a splenectomy, had an enlarged liver, and was suffering from fatigue, heart palpitations, and iron overload.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr Rondelli.”

Dr Rondelli said that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a transplant.

However, Dr Rondelli and his colleagues had reported success with chemotherapy-free allo-HSCT in patients with sickle cell disease. So Dr Rondelli performed Levy’s transplant in 2014.

Levy received a peripheral blood stem cell transplant from an unrelated donor who was a 10/10 HLA match but ABO incompatible. He received conditioning with rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.

Levy also received graft-vs-host disease (GVHD) prophylaxis consisting of high-dose cyclophosphamide, mycophenolate mofetil, and sirolimus. And he received standard antibacterial, antifungal, antiviral, and anti-Pneumocystis jiroveci prophylaxis.

Levy experienced platelet engraftment on day 20 and neutrophil engraftment on day 21. Whole-blood donor-cell chimerism was 98.7% on day 30 and 100% on day 60 and beyond.

Levy did develop transient hemolytic anemia due to the ABO incompatibility. He was given a total of 10 units of packed red blood cells until day 78.

Levy was tapered off all immunosuppression at 12 months and has shown no signs of acute or chronic GVHD.

At 24 months after HSCT, Levy’s hemoglobin was 13.7 g/dL, and his ferritin was 376 ng/mL. He has had no iron chelation since the transplant.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, who is now 35.

“I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Dr Rondelli said the potential of this treatment approach is promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias—perhaps the only possible cure,” he said.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant. This procedure gives some adults the option of a stem cell transplant, which was not previously available.”

Photo from David Levy

Physicians have reported what they believe is the first case of an allogeneic hematopoietic stem cell transplant (allo-HSCT) curing an adult with congenital dyserythropoietic anemia (CDA).

The patient, David Levy, was previously transfusion-dependent and suffered from iron overload, severe pain, and other adverse effects of his illness.

Levy was denied a transplant for years, but, in 2014, he received a non-myeloablative allo-HSCT from a matched, unrelated donor.

Now, Levy no longer requires transfusions, iron chelation, or immunosuppression, and says he is able to live a normal life.

Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues described Levy’s case in a letter to Bone Marrow Transplantation.

Levy was diagnosed with CDA at 4 months of age and was treated with regular blood transfusions for most of his life. He was 24 when the pain from his illness became so severe that he had to withdraw from graduate school.

“I spent the following years doing nothing—no work, no school, no social contact—because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every 2 to 3 weeks, had undergone a splenectomy, had an enlarged liver, and was suffering from fatigue, heart palpitations, and iron overload.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr Rondelli.”

Dr Rondelli said that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a transplant.

However, Dr Rondelli and his colleagues had reported success with chemotherapy-free allo-HSCT in patients with sickle cell disease. So Dr Rondelli performed Levy’s transplant in 2014.

Levy received a peripheral blood stem cell transplant from an unrelated donor who was a 10/10 HLA match but ABO incompatible. He received conditioning with rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.

Levy also received graft-vs-host disease (GVHD) prophylaxis consisting of high-dose cyclophosphamide, mycophenolate mofetil, and sirolimus. And he received standard antibacterial, antifungal, antiviral, and anti-Pneumocystis jiroveci prophylaxis.

Levy experienced platelet engraftment on day 20 and neutrophil engraftment on day 21. Whole-blood donor-cell chimerism was 98.7% on day 30 and 100% on day 60 and beyond.

Levy did develop transient hemolytic anemia due to the ABO incompatibility. He was given a total of 10 units of packed red blood cells until day 78.

Levy was tapered off all immunosuppression at 12 months and has shown no signs of acute or chronic GVHD.

At 24 months after HSCT, Levy’s hemoglobin was 13.7 g/dL, and his ferritin was 376 ng/mL. He has had no iron chelation since the transplant.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, who is now 35.

“I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Dr Rondelli said the potential of this treatment approach is promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias—perhaps the only possible cure,” he said.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant. This procedure gives some adults the option of a stem cell transplant, which was not previously available.”

Image by Spencer Phillips

Black individuals with sickle cell trait (SCT) have an increased risk of developing end-stage renal disease (ESRD), according to new research.

The study indicates that having SCT actually doubles the risk of ESRD.

And the trait confers a similar degree of risk as APOL1 gene variants, which are currently the most widely recognized genetic contributors to kidney disease in blacks.

Researchers believe this finding may have important public policy implications for genetic counseling for individuals with SCT.

Rakhi P. Naik, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues reported this finding in the Journal of the American Society of Nephrology.

Previous research suggested there is an association between SCT and chronic kidney disease, but it hasn’t been clear if that extends to ESRD. Studies have also suggested a possible association between kidney disease and hemoglobin C trait, but the link has not been confirmed.

So Dr Naik and her colleagues decided to investigate these potential links. To do so, the researchers analyzed data from a large, population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

The team evaluated information on 9909 black individuals, 739 of whom had SCT and 243 of whom had hemoglobin C trait.

The data indicate that individuals with SCT have a 2-fold higher risk of developing ESRD when compared to those without SCT. But there is no association between hemoglobin C trait and ESRD.

At a median follow-up of 6.5 years, the incidence of ESRD was 5.4% (40/739) in participants with SCT, 2.5% (6/243) in subjects with hemoglobin C trait, and 2.6% (234/8927) in individuals without either trait.

The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT, 3.9 per 1000 person-years for subjects with hemoglobin C trait, and 4.0 per 1000 person-years for individuals without either trait.

The researchers noted that SCT conferred a similar degree of ESRD risk as APOL1 gene variants. The hazard ratio for subjects with SCT was 2.03, and the hazard ratio for those with APOL1 high-risk genotypes was 1.77.

“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have, such as diabetes or high blood pressure,” Dr Naik said.

“We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease, specifically in individuals with sickle cell trait.”

Image by Spencer Phillips

Black individuals with sickle cell trait (SCT) have an increased risk of developing end-stage renal disease (ESRD), according to new research.

The study indicates that having SCT actually doubles the risk of ESRD.

And the trait confers a similar degree of risk as APOL1 gene variants, which are currently the most widely recognized genetic contributors to kidney disease in blacks.

Researchers believe this finding may have important public policy implications for genetic counseling for individuals with SCT.

Rakhi P. Naik, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues reported this finding in the Journal of the American Society of Nephrology.

Previous research suggested there is an association between SCT and chronic kidney disease, but it hasn’t been clear if that extends to ESRD. Studies have also suggested a possible association between kidney disease and hemoglobin C trait, but the link has not been confirmed.

So Dr Naik and her colleagues decided to investigate these potential links. To do so, the researchers analyzed data from a large, population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

The team evaluated information on 9909 black individuals, 739 of whom had SCT and 243 of whom had hemoglobin C trait.

The data indicate that individuals with SCT have a 2-fold higher risk of developing ESRD when compared to those without SCT. But there is no association between hemoglobin C trait and ESRD.

At a median follow-up of 6.5 years, the incidence of ESRD was 5.4% (40/739) in participants with SCT, 2.5% (6/243) in subjects with hemoglobin C trait, and 2.6% (234/8927) in individuals without either trait.

The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT, 3.9 per 1000 person-years for subjects with hemoglobin C trait, and 4.0 per 1000 person-years for individuals without either trait.

The researchers noted that SCT conferred a similar degree of ESRD risk as APOL1 gene variants. The hazard ratio for subjects with SCT was 2.03, and the hazard ratio for those with APOL1 high-risk genotypes was 1.77.

“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have, such as diabetes or high blood pressure,” Dr Naik said.

“We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease, specifically in individuals with sickle cell trait.”

Image by Spencer Phillips

Black individuals with sickle cell trait (SCT) have an increased risk of developing end-stage renal disease (ESRD), according to new research.

The study indicates that having SCT actually doubles the risk of ESRD.

And the trait confers a similar degree of risk as APOL1 gene variants, which are currently the most widely recognized genetic contributors to kidney disease in blacks.

Researchers believe this finding may have important public policy implications for genetic counseling for individuals with SCT.

Rakhi P. Naik, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues reported this finding in the Journal of the American Society of Nephrology.

Previous research suggested there is an association between SCT and chronic kidney disease, but it hasn’t been clear if that extends to ESRD. Studies have also suggested a possible association between kidney disease and hemoglobin C trait, but the link has not been confirmed.

So Dr Naik and her colleagues decided to investigate these potential links. To do so, the researchers analyzed data from a large, population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

The team evaluated information on 9909 black individuals, 739 of whom had SCT and 243 of whom had hemoglobin C trait.

The data indicate that individuals with SCT have a 2-fold higher risk of developing ESRD when compared to those without SCT. But there is no association between hemoglobin C trait and ESRD.

At a median follow-up of 6.5 years, the incidence of ESRD was 5.4% (40/739) in participants with SCT, 2.5% (6/243) in subjects with hemoglobin C trait, and 2.6% (234/8927) in individuals without either trait.

The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT, 3.9 per 1000 person-years for subjects with hemoglobin C trait, and 4.0 per 1000 person-years for individuals without either trait.

The researchers noted that SCT conferred a similar degree of ESRD risk as APOL1 gene variants. The hazard ratio for subjects with SCT was 2.03, and the hazard ratio for those with APOL1 high-risk genotypes was 1.77.

“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have, such as diabetes or high blood pressure,” Dr Naik said.

“We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease, specifically in individuals with sickle cell trait.”