This newsletter, Mild Persistent Asthma: Characteristics, Treatment, and Unmet Needs, discusses the characteristics and burden of mild persistent asthma and provides practical information on its diagnosis and appropriate management.

Click here to read the supplement

This newsletter, Mild Persistent Asthma: Characteristics, Treatment, and Unmet Needs, discusses the characteristics and burden of mild persistent asthma and provides practical information on its diagnosis and appropriate management.

Click here to read the supplement

This newsletter, Mild Persistent Asthma: Characteristics, Treatment, and Unmet Needs, discusses the characteristics and burden of mild persistent asthma and provides practical information on its diagnosis and appropriate management.

Click here to read the supplement

Contrary to the widespread belief that depressive disorders are more common than anxiety disorders among people with epilepsy, these psychiatric comorbidities appear to have equivalent prevalence, according to research published online ahead of print May 3 in Epilepsia. In addition, variability in the observed prevalence of anxiety disorders in previous studies partly results from the method of diagnosis.

“These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy,” said Amelia J. Scott, a PhD candidate at the University of Sydney.

Comorbid anxiety and depressive disorders are highly prevalent in patients with epilepsy, compared with the general population. The prevalence of anxiety disorders reported in previous studies of people with epilepsy has been highly variable, however. Ms. Scott and colleagues conducted a study to clarify the prevalence of anxiety and depressive disorders in patients with epilepsy and to determine which factors account for the variability in estimates of these disorders’ prevalence.

The investigators searched electronic databases to find studies that reported the prevalence of anxiety and depressive disorders in people with epilepsy until July 2016. Journal articles or dissertations that reported on current diagnoses of anxiety and depressive disorders based on a structured diagnostic interview or a clinician evaluation were included. Clinician evaluations followed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or the International Classification of Diseases, Tenth Revision or more recent.

The investigators excluded studies of participants younger than 16. In addition, studies that reported diagnoses of anxiety and depressive disorders using self-report measures and studies that only reported a depression diagnosis or only an anxiety diagnosis were also excluded. Finally, researchers excluded studies if recruitment was based on additional medical comorbidity or on results of prescreening measures of distress.

Extracted data included the prevalence of anxiety and depressive disorders and moderators of interest (eg, method of diagnosis and prevalence of drug-resistant epilepsy). Using these data, Ms. Scott and colleagues conducted a meta-analysis of the overall pooled prevalence of anxiety and depressive disorders.

In all, 27 studies met the inclusion criteria. The pooled prevalence of anxiety disorders was 20.2%, and the pooled prevalence of depressive disorders was 22.9%. Ms. Scott and colleagues also observed that the method of diagnosis significantly affected the observed prevalence of anxiety disorders. The prevalence of anxiety disorders based on unstructured clinician assessment was 8.1%, compared with a prevalence of 27.3% based on a structured clinical interview. No significant moderators of depressive disorder diagnosis were reported, however.

“Future research should aim to improve the detection and management of comorbidities in people with epilepsy, particularly anxiety disorders, which have remained relatively neglected,” said Ms. Scott. “An improvement in our understanding, detection, and management of both anxiety and depressive disorders in people with epilepsy is crucial to improve the quality of life of people with epilepsy.”

—Erica Tricarico

Suggested Reading

Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017 May 3 [Epub ahead of print].

Contrary to the widespread belief that depressive disorders are more common than anxiety disorders among people with epilepsy, these psychiatric comorbidities appear to have equivalent prevalence, according to research published online ahead of print May 3 in Epilepsia. In addition, variability in the observed prevalence of anxiety disorders in previous studies partly results from the method of diagnosis.

“These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy,” said Amelia J. Scott, a PhD candidate at the University of Sydney.

Comorbid anxiety and depressive disorders are highly prevalent in patients with epilepsy, compared with the general population. The prevalence of anxiety disorders reported in previous studies of people with epilepsy has been highly variable, however. Ms. Scott and colleagues conducted a study to clarify the prevalence of anxiety and depressive disorders in patients with epilepsy and to determine which factors account for the variability in estimates of these disorders’ prevalence.

The investigators searched electronic databases to find studies that reported the prevalence of anxiety and depressive disorders in people with epilepsy until July 2016. Journal articles or dissertations that reported on current diagnoses of anxiety and depressive disorders based on a structured diagnostic interview or a clinician evaluation were included. Clinician evaluations followed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or the International Classification of Diseases, Tenth Revision or more recent.

The investigators excluded studies of participants younger than 16. In addition, studies that reported diagnoses of anxiety and depressive disorders using self-report measures and studies that only reported a depression diagnosis or only an anxiety diagnosis were also excluded. Finally, researchers excluded studies if recruitment was based on additional medical comorbidity or on results of prescreening measures of distress.

Extracted data included the prevalence of anxiety and depressive disorders and moderators of interest (eg, method of diagnosis and prevalence of drug-resistant epilepsy). Using these data, Ms. Scott and colleagues conducted a meta-analysis of the overall pooled prevalence of anxiety and depressive disorders.

In all, 27 studies met the inclusion criteria. The pooled prevalence of anxiety disorders was 20.2%, and the pooled prevalence of depressive disorders was 22.9%. Ms. Scott and colleagues also observed that the method of diagnosis significantly affected the observed prevalence of anxiety disorders. The prevalence of anxiety disorders based on unstructured clinician assessment was 8.1%, compared with a prevalence of 27.3% based on a structured clinical interview. No significant moderators of depressive disorder diagnosis were reported, however.

“Future research should aim to improve the detection and management of comorbidities in people with epilepsy, particularly anxiety disorders, which have remained relatively neglected,” said Ms. Scott. “An improvement in our understanding, detection, and management of both anxiety and depressive disorders in people with epilepsy is crucial to improve the quality of life of people with epilepsy.”

—Erica Tricarico

Suggested Reading

Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017 May 3 [Epub ahead of print].

Contrary to the widespread belief that depressive disorders are more common than anxiety disorders among people with epilepsy, these psychiatric comorbidities appear to have equivalent prevalence, according to research published online ahead of print May 3 in Epilepsia. In addition, variability in the observed prevalence of anxiety disorders in previous studies partly results from the method of diagnosis.

“These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy,” said Amelia J. Scott, a PhD candidate at the University of Sydney.

Comorbid anxiety and depressive disorders are highly prevalent in patients with epilepsy, compared with the general population. The prevalence of anxiety disorders reported in previous studies of people with epilepsy has been highly variable, however. Ms. Scott and colleagues conducted a study to clarify the prevalence of anxiety and depressive disorders in patients with epilepsy and to determine which factors account for the variability in estimates of these disorders’ prevalence.

The investigators searched electronic databases to find studies that reported the prevalence of anxiety and depressive disorders in people with epilepsy until July 2016. Journal articles or dissertations that reported on current diagnoses of anxiety and depressive disorders based on a structured diagnostic interview or a clinician evaluation were included. Clinician evaluations followed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or the International Classification of Diseases, Tenth Revision or more recent.

The investigators excluded studies of participants younger than 16. In addition, studies that reported diagnoses of anxiety and depressive disorders using self-report measures and studies that only reported a depression diagnosis or only an anxiety diagnosis were also excluded. Finally, researchers excluded studies if recruitment was based on additional medical comorbidity or on results of prescreening measures of distress.

Extracted data included the prevalence of anxiety and depressive disorders and moderators of interest (eg, method of diagnosis and prevalence of drug-resistant epilepsy). Using these data, Ms. Scott and colleagues conducted a meta-analysis of the overall pooled prevalence of anxiety and depressive disorders.

In all, 27 studies met the inclusion criteria. The pooled prevalence of anxiety disorders was 20.2%, and the pooled prevalence of depressive disorders was 22.9%. Ms. Scott and colleagues also observed that the method of diagnosis significantly affected the observed prevalence of anxiety disorders. The prevalence of anxiety disorders based on unstructured clinician assessment was 8.1%, compared with a prevalence of 27.3% based on a structured clinical interview. No significant moderators of depressive disorder diagnosis were reported, however.

“Future research should aim to improve the detection and management of comorbidities in people with epilepsy, particularly anxiety disorders, which have remained relatively neglected,” said Ms. Scott. “An improvement in our understanding, detection, and management of both anxiety and depressive disorders in people with epilepsy is crucial to improve the quality of life of people with epilepsy.”

—Erica Tricarico

Suggested Reading

Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017 May 3 [Epub ahead of print].

Most of the postadolescent women with acne in a retrospective review of 400 patients treated over a 4-year period improved with spironolactone treatment, with a low rate of side effects, according to the authors.

“The vast majority of our patients improved on spironolactone, despite many previously failing other acne treatments,” wrote Radhika Grandhi, MD, and Ali Alikhan, MD, of the department of dermatology, University of Cincinnati. They conducted a review of 400 postadolescent female patients treated with spironolactone from July 2012 through February 2016, representing 292 patient years of experience.

Of the 400 patients, 345 improved, 27 were unchanged, 11 became worse, and 17 had an indeterminate response. Most (220 of 253 or 87%) of previously treated patients improved with spironolactone as did most (137 of 147 or 93%) of previously untreated patients.

About half of patients were on a combination of spironolactone, at least one topical agent, and an oral treatment; almost 90% of these patients improved with spironolactone. Of the remainder, 81% of those on spironolactone plus an oral medication improved, and 95% of those on spironolactone plus a topical agent improved. Of the 41 patients on spironolactone monotherapy, 35 (85%) improved.

The most common adverse effect reported was hyperkalemia in six patients, followed by facial/perioral xerosis, erythema, irritation, and pruritus in four, and one report each of severe headaches, feeling sick, heavy menstrual cycles, back pain, abdominal fullness, and breast tenderness.

These data suggest that spironolactone, a second-line acne treatment, “is a useful drug, and the results further support that spironolactone is a safe medication with tolerable side effects,” the authors noted. ‘It may be speculated that an increased use of spironolactone may decrease our dependence on oral antibiotics in acne management, which is paramount in this age of antibiotic stewardship.”

For the full study, go to (Dermatology doi: 10.1159/000471799).
 

[email protected]

Most of the postadolescent women with acne in a retrospective review of 400 patients treated over a 4-year period improved with spironolactone treatment, with a low rate of side effects, according to the authors.

“The vast majority of our patients improved on spironolactone, despite many previously failing other acne treatments,” wrote Radhika Grandhi, MD, and Ali Alikhan, MD, of the department of dermatology, University of Cincinnati. They conducted a review of 400 postadolescent female patients treated with spironolactone from July 2012 through February 2016, representing 292 patient years of experience.

Of the 400 patients, 345 improved, 27 were unchanged, 11 became worse, and 17 had an indeterminate response. Most (220 of 253 or 87%) of previously treated patients improved with spironolactone as did most (137 of 147 or 93%) of previously untreated patients.

About half of patients were on a combination of spironolactone, at least one topical agent, and an oral treatment; almost 90% of these patients improved with spironolactone. Of the remainder, 81% of those on spironolactone plus an oral medication improved, and 95% of those on spironolactone plus a topical agent improved. Of the 41 patients on spironolactone monotherapy, 35 (85%) improved.

The most common adverse effect reported was hyperkalemia in six patients, followed by facial/perioral xerosis, erythema, irritation, and pruritus in four, and one report each of severe headaches, feeling sick, heavy menstrual cycles, back pain, abdominal fullness, and breast tenderness.

These data suggest that spironolactone, a second-line acne treatment, “is a useful drug, and the results further support that spironolactone is a safe medication with tolerable side effects,” the authors noted. ‘It may be speculated that an increased use of spironolactone may decrease our dependence on oral antibiotics in acne management, which is paramount in this age of antibiotic stewardship.”

For the full study, go to (Dermatology doi: 10.1159/000471799).
 

[email protected]

Most of the postadolescent women with acne in a retrospective review of 400 patients treated over a 4-year period improved with spironolactone treatment, with a low rate of side effects, according to the authors.

“The vast majority of our patients improved on spironolactone, despite many previously failing other acne treatments,” wrote Radhika Grandhi, MD, and Ali Alikhan, MD, of the department of dermatology, University of Cincinnati. They conducted a review of 400 postadolescent female patients treated with spironolactone from July 2012 through February 2016, representing 292 patient years of experience.

Of the 400 patients, 345 improved, 27 were unchanged, 11 became worse, and 17 had an indeterminate response. Most (220 of 253 or 87%) of previously treated patients improved with spironolactone as did most (137 of 147 or 93%) of previously untreated patients.

About half of patients were on a combination of spironolactone, at least one topical agent, and an oral treatment; almost 90% of these patients improved with spironolactone. Of the remainder, 81% of those on spironolactone plus an oral medication improved, and 95% of those on spironolactone plus a topical agent improved. Of the 41 patients on spironolactone monotherapy, 35 (85%) improved.

The most common adverse effect reported was hyperkalemia in six patients, followed by facial/perioral xerosis, erythema, irritation, and pruritus in four, and one report each of severe headaches, feeling sick, heavy menstrual cycles, back pain, abdominal fullness, and breast tenderness.

These data suggest that spironolactone, a second-line acne treatment, “is a useful drug, and the results further support that spironolactone is a safe medication with tolerable side effects,” the authors noted. ‘It may be speculated that an increased use of spironolactone may decrease our dependence on oral antibiotics in acne management, which is paramount in this age of antibiotic stewardship.”

For the full study, go to (Dermatology doi: 10.1159/000471799).
 

[email protected]

LAS VEGAS – Alla Zilbering, MD, sat at attention for hours during HM17, jotting notes like a scribe about the myriad of federal rules that are pretty rapidly pushing hospitalists and health care as a whole away from fee-for-service payments to a world where doctors are paid for quality.

So, why did she do it? Why all that time on policy, instead of practice?

Because Dr. Zilbering felt compelled to get more involved. As a lead hospitalist at Cigna-HealthSpring, a Medicare Advantage program in Philadelphia, she’s already part of initiatives to improve transitions of care and reduce readmissions.

However, she said she wants to do more. “I’m feeling like, unless you actually address the policy, you can’t get that far in terms of what you can physically do with a patient.”

HM17 was the meeting for her, then. SHM, this year, unveiled its first Health Policy Mini Track, dedicated to updating attendees on the implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), the Bundled Payments for Care Improvement initiative, and a host of other federal programs. Hospitalists were updated on a litany of advocacy efforts, including observation status, interoperability of electronic health records systems, and the recent launch of the first hospitalist billing code.

Two of the meeting’s three keynote speakers were Washington veterans who confirmed that, while nightly news reports may suggest that health care reforms contained in the Affordable Care Act are constantly in flux, the trajectory toward paying for higher quality care at lower costs shows no signs of abating.

LAS VEGAS – Alla Zilbering, MD, sat at attention for hours during HM17, jotting notes like a scribe about the myriad of federal rules that are pretty rapidly pushing hospitalists and health care as a whole away from fee-for-service payments to a world where doctors are paid for quality.

So, why did she do it? Why all that time on policy, instead of practice?

Because Dr. Zilbering felt compelled to get more involved. As a lead hospitalist at Cigna-HealthSpring, a Medicare Advantage program in Philadelphia, she’s already part of initiatives to improve transitions of care and reduce readmissions.

However, she said she wants to do more. “I’m feeling like, unless you actually address the policy, you can’t get that far in terms of what you can physically do with a patient.”

HM17 was the meeting for her, then. SHM, this year, unveiled its first Health Policy Mini Track, dedicated to updating attendees on the implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), the Bundled Payments for Care Improvement initiative, and a host of other federal programs. Hospitalists were updated on a litany of advocacy efforts, including observation status, interoperability of electronic health records systems, and the recent launch of the first hospitalist billing code.

Two of the meeting’s three keynote speakers were Washington veterans who confirmed that, while nightly news reports may suggest that health care reforms contained in the Affordable Care Act are constantly in flux, the trajectory toward paying for higher quality care at lower costs shows no signs of abating.

LAS VEGAS – Alla Zilbering, MD, sat at attention for hours during HM17, jotting notes like a scribe about the myriad of federal rules that are pretty rapidly pushing hospitalists and health care as a whole away from fee-for-service payments to a world where doctors are paid for quality.

So, why did she do it? Why all that time on policy, instead of practice?

Because Dr. Zilbering felt compelled to get more involved. As a lead hospitalist at Cigna-HealthSpring, a Medicare Advantage program in Philadelphia, she’s already part of initiatives to improve transitions of care and reduce readmissions.

However, she said she wants to do more. “I’m feeling like, unless you actually address the policy, you can’t get that far in terms of what you can physically do with a patient.”

HM17 was the meeting for her, then. SHM, this year, unveiled its first Health Policy Mini Track, dedicated to updating attendees on the implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), the Bundled Payments for Care Improvement initiative, and a host of other federal programs. Hospitalists were updated on a litany of advocacy efforts, including observation status, interoperability of electronic health records systems, and the recent launch of the first hospitalist billing code.

Two of the meeting’s three keynote speakers were Washington veterans who confirmed that, while nightly news reports may suggest that health care reforms contained in the Affordable Care Act are constantly in flux, the trajectory toward paying for higher quality care at lower costs shows no signs of abating.

“Unprecedented detail” was observed about how a patient’s clinical condition changes in response to Ebola virus disease and treatment. That’s what NIH researchers who analyzed daily gene activation found in a 26-day study of 1 patient.

The patient, who was admitted to the NIH Clinical Center on day 7 of illness, received intensive supportive care, including fluids and electrolytes, but did not receive any experimental Ebola drugs. The researchers took blood samples daily to measure the rise and decline of virus replication and to track the timing, intensity, and duration of expression of numerous immune system genes. They correlated changes in gene expression with subsequent alterations in the patient’s clinical condition, such as development and resolution of blood-clotting dysfunction.

The researchers pinpointed “key transition points” in the response to infection, NIH says. For example, they observed a marked decline in antiviral responses that correlated with clearance of virus from white blood cells. The researchers also found that most host responses shifted rapidly from activating genes involved in cell damage and inflammation toward those linked to promotion of cellular and organ repair—a “pivot” that came before the patient began showing signs of clinical improvement.

Although the study centered on only 1 patient, the researchers say it may help inform the development of treatments designed to boost or accelerate host factors that counter the virus and promote healing.

“Unprecedented detail” was observed about how a patient’s clinical condition changes in response to Ebola virus disease and treatment. That’s what NIH researchers who analyzed daily gene activation found in a 26-day study of 1 patient.

The patient, who was admitted to the NIH Clinical Center on day 7 of illness, received intensive supportive care, including fluids and electrolytes, but did not receive any experimental Ebola drugs. The researchers took blood samples daily to measure the rise and decline of virus replication and to track the timing, intensity, and duration of expression of numerous immune system genes. They correlated changes in gene expression with subsequent alterations in the patient’s clinical condition, such as development and resolution of blood-clotting dysfunction.

The researchers pinpointed “key transition points” in the response to infection, NIH says. For example, they observed a marked decline in antiviral responses that correlated with clearance of virus from white blood cells. The researchers also found that most host responses shifted rapidly from activating genes involved in cell damage and inflammation toward those linked to promotion of cellular and organ repair—a “pivot” that came before the patient began showing signs of clinical improvement.

Although the study centered on only 1 patient, the researchers say it may help inform the development of treatments designed to boost or accelerate host factors that counter the virus and promote healing.

“Unprecedented detail” was observed about how a patient’s clinical condition changes in response to Ebola virus disease and treatment. That’s what NIH researchers who analyzed daily gene activation found in a 26-day study of 1 patient.

The patient, who was admitted to the NIH Clinical Center on day 7 of illness, received intensive supportive care, including fluids and electrolytes, but did not receive any experimental Ebola drugs. The researchers took blood samples daily to measure the rise and decline of virus replication and to track the timing, intensity, and duration of expression of numerous immune system genes. They correlated changes in gene expression with subsequent alterations in the patient’s clinical condition, such as development and resolution of blood-clotting dysfunction.

The researchers pinpointed “key transition points” in the response to infection, NIH says. For example, they observed a marked decline in antiviral responses that correlated with clearance of virus from white blood cells. The researchers also found that most host responses shifted rapidly from activating genes involved in cell damage and inflammation toward those linked to promotion of cellular and organ repair—a “pivot” that came before the patient began showing signs of clinical improvement.

Although the study centered on only 1 patient, the researchers say it may help inform the development of treatments designed to boost or accelerate host factors that counter the virus and promote healing.

Cardiac tumors are rare and usually benign. An exception is the primary cardiac schwannoma.  Only 17 cases have been reported, and most of those were malignant, say a team of doctors from McMaster University and Hamilton General Hospital, both in Ontario, Canada. Schwannomas, composed of Schwann cells, are tumors of nerve sheaths commonly found in cranial and peripheral nerves. The clinicians’ account of an “interesting case” of a patient with a benign schwannoma was unusual—and the fact that it was in the heart makes it “exceedingly rare.”

Related: Tracking a Tumor

Their patient, a 47-year-old woman who had been treated for ovarian cancer, had no symptoms of a cardiac schwannoma. During the workup for the ovarian cancer, the clinicians discovered a large mass between the right atrium and right ventricle. Because she was asymptomatic, her physicians decided to closely monitor the tumor’s growth.

The chemotherapy for ovarian cancer did not reduce the cardiac schwannoma. As the disease progressed and the tumor grew, the patient developed symptoms, including sharp chest pain, shortness of breath, and palpitations.

Related: Rare Cancer Gets Timely Right Treatment

The prognosis of benign cardiac tumor depends on resectability, the clinicians say. After complete resection the prognosis is excellent, and adjuvant therapy is not needed. If surgery is not indicated, chemotherapy is an option. The patient chose to have surgery to remove the tumor. During the operation, the surgeons found that the blood supply of the tumor came from a branch of the right coronary artery and the posterior descending artery (PDA).

The surgery, which included resection, ligation of the PDA , and a saphenous vein graft for a coronary bypass to the distal PDA, was successful. A definite diagnosis of cardiac tumors can be completed only after histologic examination of samples taken at autopsy or surgical resection, the clinicians note. The gross and microscopic evidence confirmed diagnosis of benign schwannoma of the heart.

Related: In Rare Case Colorectal Cancer Causes Thrombus

Source:
Koujanian S, Pawlowicz B, Landry D, Alexopoulou I, Nair V. Hum Pathol. 2017;(8):24-26

Cardiac tumors are rare and usually benign. An exception is the primary cardiac schwannoma.  Only 17 cases have been reported, and most of those were malignant, say a team of doctors from McMaster University and Hamilton General Hospital, both in Ontario, Canada. Schwannomas, composed of Schwann cells, are tumors of nerve sheaths commonly found in cranial and peripheral nerves. The clinicians’ account of an “interesting case” of a patient with a benign schwannoma was unusual—and the fact that it was in the heart makes it “exceedingly rare.”

Related: Tracking a Tumor

Their patient, a 47-year-old woman who had been treated for ovarian cancer, had no symptoms of a cardiac schwannoma. During the workup for the ovarian cancer, the clinicians discovered a large mass between the right atrium and right ventricle. Because she was asymptomatic, her physicians decided to closely monitor the tumor’s growth.

The chemotherapy for ovarian cancer did not reduce the cardiac schwannoma. As the disease progressed and the tumor grew, the patient developed symptoms, including sharp chest pain, shortness of breath, and palpitations.

Related: Rare Cancer Gets Timely Right Treatment

The prognosis of benign cardiac tumor depends on resectability, the clinicians say. After complete resection the prognosis is excellent, and adjuvant therapy is not needed. If surgery is not indicated, chemotherapy is an option. The patient chose to have surgery to remove the tumor. During the operation, the surgeons found that the blood supply of the tumor came from a branch of the right coronary artery and the posterior descending artery (PDA).

The surgery, which included resection, ligation of the PDA , and a saphenous vein graft for a coronary bypass to the distal PDA, was successful. A definite diagnosis of cardiac tumors can be completed only after histologic examination of samples taken at autopsy or surgical resection, the clinicians note. The gross and microscopic evidence confirmed diagnosis of benign schwannoma of the heart.

Related: In Rare Case Colorectal Cancer Causes Thrombus

Source:
Koujanian S, Pawlowicz B, Landry D, Alexopoulou I, Nair V. Hum Pathol. 2017;(8):24-26

Cardiac tumors are rare and usually benign. An exception is the primary cardiac schwannoma.  Only 17 cases have been reported, and most of those were malignant, say a team of doctors from McMaster University and Hamilton General Hospital, both in Ontario, Canada. Schwannomas, composed of Schwann cells, are tumors of nerve sheaths commonly found in cranial and peripheral nerves. The clinicians’ account of an “interesting case” of a patient with a benign schwannoma was unusual—and the fact that it was in the heart makes it “exceedingly rare.”

Related: Tracking a Tumor

Their patient, a 47-year-old woman who had been treated for ovarian cancer, had no symptoms of a cardiac schwannoma. During the workup for the ovarian cancer, the clinicians discovered a large mass between the right atrium and right ventricle. Because she was asymptomatic, her physicians decided to closely monitor the tumor’s growth.

The chemotherapy for ovarian cancer did not reduce the cardiac schwannoma. As the disease progressed and the tumor grew, the patient developed symptoms, including sharp chest pain, shortness of breath, and palpitations.

Related: Rare Cancer Gets Timely Right Treatment

The prognosis of benign cardiac tumor depends on resectability, the clinicians say. After complete resection the prognosis is excellent, and adjuvant therapy is not needed. If surgery is not indicated, chemotherapy is an option. The patient chose to have surgery to remove the tumor. During the operation, the surgeons found that the blood supply of the tumor came from a branch of the right coronary artery and the posterior descending artery (PDA).

The surgery, which included resection, ligation of the PDA , and a saphenous vein graft for a coronary bypass to the distal PDA, was successful. A definite diagnosis of cardiac tumors can be completed only after histologic examination of samples taken at autopsy or surgical resection, the clinicians note. The gross and microscopic evidence confirmed diagnosis of benign schwannoma of the heart.

Related: In Rare Case Colorectal Cancer Causes Thrombus

Source:
Koujanian S, Pawlowicz B, Landry D, Alexopoulou I, Nair V. Hum Pathol. 2017;(8):24-26

Hematopoietic stem cells in the bone marrow

Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).

The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.

In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.

“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.

“This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.

Drs Scandura and Rafii and their colleagues described this research in Nature.

The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.

The cells were grown and multiplied in co-culture with an engineered vascular niche.

This produced HSCs that were transplanted into irradiated mice.

The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.

In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.

If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.

“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”

“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.” 

Hematopoietic stem cells in the bone marrow

Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).

The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.

In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.

“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.

“This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.

Drs Scandura and Rafii and their colleagues described this research in Nature.

The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.

The cells were grown and multiplied in co-culture with an engineered vascular niche.

This produced HSCs that were transplanted into irradiated mice.

The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.

In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.

If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.

“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”

“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.” 

Hematopoietic stem cells in the bone marrow

Researchers say they have found a way to convert adult mouse endothelial cells into “authentic” hematopoietic stem cells (HSCs).

The team says these HSCs have a transcriptome and long-term self-renewal capacity that are similar to those of adult HSCs that are produced naturally.

In addition, the lab-generated HSCs were capable of engraftment and multi-lineage reconstitution in mice.

“This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also to deciphering the complex biology of stem-cell self-renewal machinery,” said Shahin Rafii, MD, of Weill Cornell Medicine in New York, New York.

“This is exciting because it provides us with a path towards generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added Joseph Scandura, MD, PhD, also of Weill Cornell Medicine.

Drs Scandura and Rafii and their colleagues described this research in Nature.

The researchers took vascular endothelial cells from adult mice and induced expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1.

The cells were grown and multiplied in co-culture with an engineered vascular niche.

This produced HSCs that were transplanted into irradiated mice.

The researchers said these HSCs were capable of long-term engraftment and hematopoietic reconstitution of myelopoiesis and both innate and adaptive immune function.

In addition, the HSCs were endowed with the same genetic attributes as normal adult HSCs.

If this method of generating HSCs in the lab can be scaled up and applied to humans, it could have wide-ranging clinical implications, according to the researchers.

“It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Dr Scandura said. “It could lead to new ways to cure leukemia and may help us correct genetic defects that cause blood diseases like sickle cell anemia.”

“More importantly, our vascular niche stem cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Dr Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.” 

mycosis fungoides

The European Commission (EC) has granted orphan designation to MRG-106 for the treatment of cutaneous T-cell lymphoma (CTCL).

MRG-106 is a locked nucleic acid-modified oligonucleotide inhibitor of miR-155-5p.

miRagen Therapeutics, Inc., the company developing MRG-106, is currently testing the drug in a phase 1 trial of CTCL patients.

Early results from this trial were presented at the 2016 ASH Annual Meeting.

Researchers presented results in 6 patients with stage I-III mycosis fungoides.

The patients received 4 or 5 intratumoral injections of MRG-106 (at 75 mg) over 2 weeks. Four patients received saline injections in a second lesion on the same schedule.

There were 3 adverse events related to MRG-106—pain during injection, burning sensation during injection, and tingling at the injection site.

Adverse events considered possibly related to MRG-106 were pruritus, erythema, skin inflammation, sore on hand, nausea, decrease in white blood cells, neutropenia, and prolonged partial thromboplastin time.

One patient was taken off the trial due to rapid disease progression. The other 5 patients completed the dosing period.

All 5 patients had a reduction in the baseline Composite Assessment of Index Lesion Severity score in MRG-106-treated and saline-treated lesions.

The average maximal reduction was 55% (range, 33% to 77%) in MRG-106-treated lesions and 39% (range, 13% to 75%) in saline-treated lesions.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

mycosis fungoides

The European Commission (EC) has granted orphan designation to MRG-106 for the treatment of cutaneous T-cell lymphoma (CTCL).

MRG-106 is a locked nucleic acid-modified oligonucleotide inhibitor of miR-155-5p.

miRagen Therapeutics, Inc., the company developing MRG-106, is currently testing the drug in a phase 1 trial of CTCL patients.

Early results from this trial were presented at the 2016 ASH Annual Meeting.

Researchers presented results in 6 patients with stage I-III mycosis fungoides.

The patients received 4 or 5 intratumoral injections of MRG-106 (at 75 mg) over 2 weeks. Four patients received saline injections in a second lesion on the same schedule.

There were 3 adverse events related to MRG-106—pain during injection, burning sensation during injection, and tingling at the injection site.

Adverse events considered possibly related to MRG-106 were pruritus, erythema, skin inflammation, sore on hand, nausea, decrease in white blood cells, neutropenia, and prolonged partial thromboplastin time.

One patient was taken off the trial due to rapid disease progression. The other 5 patients completed the dosing period.

All 5 patients had a reduction in the baseline Composite Assessment of Index Lesion Severity score in MRG-106-treated and saline-treated lesions.

The average maximal reduction was 55% (range, 33% to 77%) in MRG-106-treated lesions and 39% (range, 13% to 75%) in saline-treated lesions.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

mycosis fungoides

The European Commission (EC) has granted orphan designation to MRG-106 for the treatment of cutaneous T-cell lymphoma (CTCL).

MRG-106 is a locked nucleic acid-modified oligonucleotide inhibitor of miR-155-5p.

miRagen Therapeutics, Inc., the company developing MRG-106, is currently testing the drug in a phase 1 trial of CTCL patients.

Early results from this trial were presented at the 2016 ASH Annual Meeting.

Researchers presented results in 6 patients with stage I-III mycosis fungoides.

The patients received 4 or 5 intratumoral injections of MRG-106 (at 75 mg) over 2 weeks. Four patients received saline injections in a second lesion on the same schedule.

There were 3 adverse events related to MRG-106—pain during injection, burning sensation during injection, and tingling at the injection site.

Adverse events considered possibly related to MRG-106 were pruritus, erythema, skin inflammation, sore on hand, nausea, decrease in white blood cells, neutropenia, and prolonged partial thromboplastin time.

One patient was taken off the trial due to rapid disease progression. The other 5 patients completed the dosing period.

All 5 patients had a reduction in the baseline Composite Assessment of Index Lesion Severity score in MRG-106-treated and saline-treated lesions.

The average maximal reduction was 55% (range, 33% to 77%) in MRG-106-treated lesions and 39% (range, 13% to 75%) in saline-treated lesions.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

Photo by Elise Amendola

Blood banks in countries that accept the CE mark can now use the Procleix Zika Virus Assay to screen blood donations for the presence of Zika virus.

CE marking means a product conforms to relevant legislation for sale in the European economic area.

The Procleix Zika Virus Assay, which was developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System, an automated, nucleic acid technology (NAT) blood screening platform.

NAT enables detection of infectious agents in blood and plasma donations.

The Procleix Panther system automates all aspects of NAT-based blood screening on a single, integrated platform.

The system has received regulatory approvals in countries around the world, and it is in development for the US market.

In the US, the Procleix Zika Virus Assay is being used under an investigational new drug protocol in response to the US Food and Drug Administration’s recommendation to screen all US blood donations for Zika virus.

“The CE marking of the Procleix Zika virus assay is a further step in our mission to support safer blood donations, the result of our passion for innovation and the role we play as market leaders in transfusion medicine,” said Grifols Diagnostic Division President Carsten Schroeder.

About Zika virus

Zika is a mosquito-borne virus that was first identified in rhesus monkeys in Uganda in 1947 and in humans in 1952. Outbreaks of Zika virus have been recorded in Africa, the Americas, Asia, and the Pacific.

Zika virus is transmitted to humans primarily through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti, in tropical regions.

Sexual transmission of Zika virus is also possible, and reports have suggested Zika can be transmitted via transfusion of blood products. Other modes of transmission are being investigated as well.

In total, 64 countries and territories have reported transmission of Zika virus since January 1, 2007. 

Photo by Elise Amendola

Blood banks in countries that accept the CE mark can now use the Procleix Zika Virus Assay to screen blood donations for the presence of Zika virus.

CE marking means a product conforms to relevant legislation for sale in the European economic area.

The Procleix Zika Virus Assay, which was developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System, an automated, nucleic acid technology (NAT) blood screening platform.

NAT enables detection of infectious agents in blood and plasma donations.

The Procleix Panther system automates all aspects of NAT-based blood screening on a single, integrated platform.

The system has received regulatory approvals in countries around the world, and it is in development for the US market.

In the US, the Procleix Zika Virus Assay is being used under an investigational new drug protocol in response to the US Food and Drug Administration’s recommendation to screen all US blood donations for Zika virus.

“The CE marking of the Procleix Zika virus assay is a further step in our mission to support safer blood donations, the result of our passion for innovation and the role we play as market leaders in transfusion medicine,” said Grifols Diagnostic Division President Carsten Schroeder.

About Zika virus

Zika is a mosquito-borne virus that was first identified in rhesus monkeys in Uganda in 1947 and in humans in 1952. Outbreaks of Zika virus have been recorded in Africa, the Americas, Asia, and the Pacific.

Zika virus is transmitted to humans primarily through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti, in tropical regions.

Sexual transmission of Zika virus is also possible, and reports have suggested Zika can be transmitted via transfusion of blood products. Other modes of transmission are being investigated as well.

In total, 64 countries and territories have reported transmission of Zika virus since January 1, 2007. 

Photo by Elise Amendola

Blood banks in countries that accept the CE mark can now use the Procleix Zika Virus Assay to screen blood donations for the presence of Zika virus.

CE marking means a product conforms to relevant legislation for sale in the European economic area.

The Procleix Zika Virus Assay, which was developed by Hologic, Inc. and Grifols, is designed to run on the Procleix Panther System, an automated, nucleic acid technology (NAT) blood screening platform.

NAT enables detection of infectious agents in blood and plasma donations.

The Procleix Panther system automates all aspects of NAT-based blood screening on a single, integrated platform.

The system has received regulatory approvals in countries around the world, and it is in development for the US market.

In the US, the Procleix Zika Virus Assay is being used under an investigational new drug protocol in response to the US Food and Drug Administration’s recommendation to screen all US blood donations for Zika virus.

“The CE marking of the Procleix Zika virus assay is a further step in our mission to support safer blood donations, the result of our passion for innovation and the role we play as market leaders in transfusion medicine,” said Grifols Diagnostic Division President Carsten Schroeder.

About Zika virus

Zika is a mosquito-borne virus that was first identified in rhesus monkeys in Uganda in 1947 and in humans in 1952. Outbreaks of Zika virus have been recorded in Africa, the Americas, Asia, and the Pacific.

Zika virus is transmitted to humans primarily through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti, in tropical regions.

Sexual transmission of Zika virus is also possible, and reports have suggested Zika can be transmitted via transfusion of blood products. Other modes of transmission are being investigated as well.

In total, 64 countries and territories have reported transmission of Zika virus since January 1, 2007. 

AML cells

The European Medicines Agency (EMA) has recommended orphan designation for Actimab-A, a product intended to treat patients with newly diagnosed acute myeloid leukemia (AML) who are over the age of 60 and are ineligible for standard induction therapy.

Actimab-A targets CD33, a protein expressed on the surface of AML cells, via the monoclonal antibody, HuM195, which carries the cytotoxic radioisotope actinium-225 to the AML cells.

Actinium Pharmaceuticals, Inc., the company developing Actimab-A, is testing the drug in a phase 2 trial.

Results from a phase 1 trial of the drug were presented at the 2016 ASH Annual Meeting.

At that time, researchers reported results in 18 patients who had been newly diagnosed with AML and were age 60 and older. Their median age was 77 (range, 68-87).

The patients received Actimab-A in combination with low-dose cytarabine. Actimab-A was given at 0.5 μCi/kg/fraction (n=3), 1 μCi/kg/fraction (n=6), 1.5 μCi/kg/fraction (n=3), or 2 μCi/kg/fraction (n=6).

Two patients experienced dose-limiting toxicities. Both had grade 4 thrombocytopenia with marrow aplasia for more than 6 weeks after therapy. One patient was in the 1 µCi/kg/fraction cohort, and the other was in the 2 µCi/kg/fraction cohort.

The maximum-tolerated dose was not reached, but 2 µCi/kg/fraction was chosen as the phase 2 dose.

Grade 3/4 toxicities included neutropenia (n=5), thrombocytopenia (n=9), febrile neutropenia (n=6), pneumonia (n=5), other infections (n=3), atrial fibrillation/syncope (n=1), transient creatinine increase (n=1), generalized fatigue (n=1), hypokalemia (n=1), mucositis (n=1), and rectal hemorrhage (n=1).

Twenty-eight percent of patients (5/18) had objective responses to treatment. Two patients achieved a complete response (CR), 1 had a CR with incomplete platelet recovery, and 2 had a CR with incomplete marrow recovery.

The median duration of response was 9.1 months (range, 4.1-16.9).

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days. 

AML cells

The European Medicines Agency (EMA) has recommended orphan designation for Actimab-A, a product intended to treat patients with newly diagnosed acute myeloid leukemia (AML) who are over the age of 60 and are ineligible for standard induction therapy.

Actimab-A targets CD33, a protein expressed on the surface of AML cells, via the monoclonal antibody, HuM195, which carries the cytotoxic radioisotope actinium-225 to the AML cells.

Actinium Pharmaceuticals, Inc., the company developing Actimab-A, is testing the drug in a phase 2 trial.

Results from a phase 1 trial of the drug were presented at the 2016 ASH Annual Meeting.

At that time, researchers reported results in 18 patients who had been newly diagnosed with AML and were age 60 and older. Their median age was 77 (range, 68-87).

The patients received Actimab-A in combination with low-dose cytarabine. Actimab-A was given at 0.5 μCi/kg/fraction (n=3), 1 μCi/kg/fraction (n=6), 1.5 μCi/kg/fraction (n=3), or 2 μCi/kg/fraction (n=6).

Two patients experienced dose-limiting toxicities. Both had grade 4 thrombocytopenia with marrow aplasia for more than 6 weeks after therapy. One patient was in the 1 µCi/kg/fraction cohort, and the other was in the 2 µCi/kg/fraction cohort.

The maximum-tolerated dose was not reached, but 2 µCi/kg/fraction was chosen as the phase 2 dose.

Grade 3/4 toxicities included neutropenia (n=5), thrombocytopenia (n=9), febrile neutropenia (n=6), pneumonia (n=5), other infections (n=3), atrial fibrillation/syncope (n=1), transient creatinine increase (n=1), generalized fatigue (n=1), hypokalemia (n=1), mucositis (n=1), and rectal hemorrhage (n=1).

Twenty-eight percent of patients (5/18) had objective responses to treatment. Two patients achieved a complete response (CR), 1 had a CR with incomplete platelet recovery, and 2 had a CR with incomplete marrow recovery.

The median duration of response was 9.1 months (range, 4.1-16.9).

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days. 

AML cells

The European Medicines Agency (EMA) has recommended orphan designation for Actimab-A, a product intended to treat patients with newly diagnosed acute myeloid leukemia (AML) who are over the age of 60 and are ineligible for standard induction therapy.

Actimab-A targets CD33, a protein expressed on the surface of AML cells, via the monoclonal antibody, HuM195, which carries the cytotoxic radioisotope actinium-225 to the AML cells.

Actinium Pharmaceuticals, Inc., the company developing Actimab-A, is testing the drug in a phase 2 trial.

Results from a phase 1 trial of the drug were presented at the 2016 ASH Annual Meeting.

At that time, researchers reported results in 18 patients who had been newly diagnosed with AML and were age 60 and older. Their median age was 77 (range, 68-87).

The patients received Actimab-A in combination with low-dose cytarabine. Actimab-A was given at 0.5 μCi/kg/fraction (n=3), 1 μCi/kg/fraction (n=6), 1.5 μCi/kg/fraction (n=3), or 2 μCi/kg/fraction (n=6).

Two patients experienced dose-limiting toxicities. Both had grade 4 thrombocytopenia with marrow aplasia for more than 6 weeks after therapy. One patient was in the 1 µCi/kg/fraction cohort, and the other was in the 2 µCi/kg/fraction cohort.

The maximum-tolerated dose was not reached, but 2 µCi/kg/fraction was chosen as the phase 2 dose.

Grade 3/4 toxicities included neutropenia (n=5), thrombocytopenia (n=9), febrile neutropenia (n=6), pneumonia (n=5), other infections (n=3), atrial fibrillation/syncope (n=1), transient creatinine increase (n=1), generalized fatigue (n=1), hypokalemia (n=1), mucositis (n=1), and rectal hemorrhage (n=1).

Twenty-eight percent of patients (5/18) had objective responses to treatment. Two patients achieved a complete response (CR), 1 had a CR with incomplete platelet recovery, and 2 had a CR with incomplete marrow recovery.

The median duration of response was 9.1 months (range, 4.1-16.9).

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.