Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

I am a relatively young physician. When I started medical school 10 years ago, I thought that most medical school campuses would be fairly progressive. This was not the case for me.

My school did not have a nondiscrimination policy on sexual orientation or gender identity at the time, nor do I recall any lectures about this patient population. So during my first year of medical school, I embarked on a mission to educate both my classmates and the faculty about sexual orientation, gender identity, and related health disparities. My fellow classmates and the administration received my efforts warmly; nevertheless, this effort to educate was an incredible challenge for me. Surely other medical school campuses were already discussing the importance of sexuality and gender identity, I thought.

Fast forward to the year 2011. A study in JAMA found that many medical schools fall short in teaching the next generation of physicians about lesbian, gay, bisexual, and transgender (LGBT) health (JAMA. 2011;306[9]:971-7).

Things may have improved for LGBT people, but the world of medicine has yet to catch up. If LGBT medical education is lacking today, imagine how lacking it was for those who went to medical school decades ago. It is my hope that with this new column, we as a medical community can make up for lost time.

Why should physicians, especially pediatricians, care about LGBT health? Although LGBT youth comprise less than 10% of the adolescent population, they have a disproportionate share of health problems compared with their heterosexual peers. LGBT youth are three times as likely to attempt suicide and almost two times as likely to abuse alcohol and drugs compared with heterosexual youth. Among homeless teens in the United States, a whopping 40% are LGBT. HIV still plagues young gay males – especially those of color – and young gay and bisexual women experience an inordinate amount of dating violence from both men and women. Most appalling of all, every 3 days, a transgender person is murdered. These sobering statistics highlight the impact sexual orientation and gender identity have on health.

Why do LGBT youth experience such enormous health problems? A rich body of evidence points to stigma and discrimination as a likely cause. We are familiar with stories of how LGBT youth are kicked out of their homes after coming out to their parents or how male teens suffered bullying for being perceived as “too feminine.” Nonetheless, we tend to ignore the more subtle ways LGBT youth experience stigma and discrimination through our heterosexist language and behavior. Although we could dismiss the phrase “that’s so gay” as just another variation of “that’s so dumb,” an LGBT teen might think “if something is that dumb, then so am I.”

My fellow columnists and I hope that this column will help you get to know a very vulnerable, yet special, population. We will ask you to rethink what you have learned about sexuality and gender. Here, we will start with the basics.

What is the difference between sex and gender?

Sex is the biological distinction between male and female that is determined chromosomally (XX versus XY, although there are variations) and phenotypically, such as organs like the penis or vagina. Gender is a range of characteristics that a culture assigns as typically male and female, which encompasses both anatomy and behaviors. For example, an individual assigned as male because he was born with a penis is also expected to be proactive, a problem solver, stoic, and the breadwinner of the family. Although we’d like to believe that there are clear distinctions between the two solely on the basis of anatomy, we often see many people diverge from behaviors that are typically assigned to a gender. In modern day U.S. society, there are an increasing number of men who stay home to take care of their children – a typically female role. In other words, gender is a spectrum ranging from the very masculine to the very feminine and everything else in between.

What is gender identity?

Gender identity is our own sense of maleness or femaleness. This identity can be based on a variety of factors, including the sex organ one is born with and the culture one is raised in. It also is possible for some people to feel that they do not fit neatly into male or female categories. At the end of the day, only you can determine your gender identity, despite beliefs and attitudes in society about which appearances and behaviors are stereotypically male or female.

Transgender people are individuals who experience a mismatch between their gender identity and their assigned sex at birth. The word “trans” is Latin for “the other side,” highlighting the discrepancy between one’s gender identity and assigned sex. In contrast, people who identify as their assigned sex would be called cisgender. The word “cis” is Latin for “the same side.” A transgender male is someone who was assigned female at birth, but identifies as a male, whereas a transgender female is someone who was assigned male at birth, but identifies as a female. You also may also hear the terms “FTM” (female to male) and “MTF” (male to female) to describe transgender males and females, respectively.

What is sexual orientation?

Sexual orientation refers to our pattern of emotional and/or physical attraction to people who are the same or the opposite gender. The most common in this society is heterosexual, where one finds the opposite gender attractive. Those who identify as gay or lesbian find the same gender attractive. A person who identifies as bisexual finds both genders attractive. There are other sexual orientations that are not as commonly known. Someone who is pansexual is attracted to any sex or gender identity. Asexuals are individuals who don’t find anyone sexually attractive, but could be attracted to someone romantically or emotionally irrespective of sex or gender.

Just as gender is fluid, so is sexuality. Alfred Kinsey, a well-known sexologist, introduced the concept of sexual fluidity with the Kinsey Scale. With this scale, people rate themselves on how attracted they are to each sex, ranging from 0 – meaning exclusively attracted to the opposite sex – to 3 – equally attracted to both sexes – to 6 – exclusively attracted to the same sex. It is possible to move along the spectrum in either direction over time or stay in one place. It is also possible for our sexual identity (i.e. lesbian, gay, bisexual) and sexual behavior (i.e. whom we are having sex with) to not perfectly overlap; attraction is complex. Finally, people often confuse gender identity and sexual orientation. These are two separate concepts and not dependent on each other. For example, someone who was assigned female at birth but now identifies as male can still be attracted to men.

This primer is by no means complete or comprehensive and runs the risk of being oversimplistic. Nevertheless, I hope it will get you thinking about the nature of sexuality and gender identity and how they affect health. In the next couple of months, you will read more on the complexities of sexuality and gender identity, advice on how to talk to your patients about these topics, how to make your clinic a safe place for LGBT youth, the transition process for transgender youth, and much more. I encourage you stick around to learn how you can help this vulnerable, but amazing, group of young people. Until next time …

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh.

I am a relatively young physician. When I started medical school 10 years ago, I thought that most medical school campuses would be fairly progressive. This was not the case for me.

My school did not have a nondiscrimination policy on sexual orientation or gender identity at the time, nor do I recall any lectures about this patient population. So during my first year of medical school, I embarked on a mission to educate both my classmates and the faculty about sexual orientation, gender identity, and related health disparities. My fellow classmates and the administration received my efforts warmly; nevertheless, this effort to educate was an incredible challenge for me. Surely other medical school campuses were already discussing the importance of sexuality and gender identity, I thought.

Fast forward to the year 2011. A study in JAMA found that many medical schools fall short in teaching the next generation of physicians about lesbian, gay, bisexual, and transgender (LGBT) health (JAMA. 2011;306[9]:971-7).

Things may have improved for LGBT people, but the world of medicine has yet to catch up. If LGBT medical education is lacking today, imagine how lacking it was for those who went to medical school decades ago. It is my hope that with this new column, we as a medical community can make up for lost time.

Why should physicians, especially pediatricians, care about LGBT health? Although LGBT youth comprise less than 10% of the adolescent population, they have a disproportionate share of health problems compared with their heterosexual peers. LGBT youth are three times as likely to attempt suicide and almost two times as likely to abuse alcohol and drugs compared with heterosexual youth. Among homeless teens in the United States, a whopping 40% are LGBT. HIV still plagues young gay males – especially those of color – and young gay and bisexual women experience an inordinate amount of dating violence from both men and women. Most appalling of all, every 3 days, a transgender person is murdered. These sobering statistics highlight the impact sexual orientation and gender identity have on health.

Why do LGBT youth experience such enormous health problems? A rich body of evidence points to stigma and discrimination as a likely cause. We are familiar with stories of how LGBT youth are kicked out of their homes after coming out to their parents or how male teens suffered bullying for being perceived as “too feminine.” Nonetheless, we tend to ignore the more subtle ways LGBT youth experience stigma and discrimination through our heterosexist language and behavior. Although we could dismiss the phrase “that’s so gay” as just another variation of “that’s so dumb,” an LGBT teen might think “if something is that dumb, then so am I.”

My fellow columnists and I hope that this column will help you get to know a very vulnerable, yet special, population. We will ask you to rethink what you have learned about sexuality and gender. Here, we will start with the basics.

What is the difference between sex and gender?

Sex is the biological distinction between male and female that is determined chromosomally (XX versus XY, although there are variations) and phenotypically, such as organs like the penis or vagina. Gender is a range of characteristics that a culture assigns as typically male and female, which encompasses both anatomy and behaviors. For example, an individual assigned as male because he was born with a penis is also expected to be proactive, a problem solver, stoic, and the breadwinner of the family. Although we’d like to believe that there are clear distinctions between the two solely on the basis of anatomy, we often see many people diverge from behaviors that are typically assigned to a gender. In modern day U.S. society, there are an increasing number of men who stay home to take care of their children – a typically female role. In other words, gender is a spectrum ranging from the very masculine to the very feminine and everything else in between.

What is gender identity?

Gender identity is our own sense of maleness or femaleness. This identity can be based on a variety of factors, including the sex organ one is born with and the culture one is raised in. It also is possible for some people to feel that they do not fit neatly into male or female categories. At the end of the day, only you can determine your gender identity, despite beliefs and attitudes in society about which appearances and behaviors are stereotypically male or female.

Transgender people are individuals who experience a mismatch between their gender identity and their assigned sex at birth. The word “trans” is Latin for “the other side,” highlighting the discrepancy between one’s gender identity and assigned sex. In contrast, people who identify as their assigned sex would be called cisgender. The word “cis” is Latin for “the same side.” A transgender male is someone who was assigned female at birth, but identifies as a male, whereas a transgender female is someone who was assigned male at birth, but identifies as a female. You also may also hear the terms “FTM” (female to male) and “MTF” (male to female) to describe transgender males and females, respectively.

What is sexual orientation?

Sexual orientation refers to our pattern of emotional and/or physical attraction to people who are the same or the opposite gender. The most common in this society is heterosexual, where one finds the opposite gender attractive. Those who identify as gay or lesbian find the same gender attractive. A person who identifies as bisexual finds both genders attractive. There are other sexual orientations that are not as commonly known. Someone who is pansexual is attracted to any sex or gender identity. Asexuals are individuals who don’t find anyone sexually attractive, but could be attracted to someone romantically or emotionally irrespective of sex or gender.

Just as gender is fluid, so is sexuality. Alfred Kinsey, a well-known sexologist, introduced the concept of sexual fluidity with the Kinsey Scale. With this scale, people rate themselves on how attracted they are to each sex, ranging from 0 – meaning exclusively attracted to the opposite sex – to 3 – equally attracted to both sexes – to 6 – exclusively attracted to the same sex. It is possible to move along the spectrum in either direction over time or stay in one place. It is also possible for our sexual identity (i.e. lesbian, gay, bisexual) and sexual behavior (i.e. whom we are having sex with) to not perfectly overlap; attraction is complex. Finally, people often confuse gender identity and sexual orientation. These are two separate concepts and not dependent on each other. For example, someone who was assigned female at birth but now identifies as male can still be attracted to men.

This primer is by no means complete or comprehensive and runs the risk of being oversimplistic. Nevertheless, I hope it will get you thinking about the nature of sexuality and gender identity and how they affect health. In the next couple of months, you will read more on the complexities of sexuality and gender identity, advice on how to talk to your patients about these topics, how to make your clinic a safe place for LGBT youth, the transition process for transgender youth, and much more. I encourage you stick around to learn how you can help this vulnerable, but amazing, group of young people. Until next time …

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh.

I am a relatively young physician. When I started medical school 10 years ago, I thought that most medical school campuses would be fairly progressive. This was not the case for me.

My school did not have a nondiscrimination policy on sexual orientation or gender identity at the time, nor do I recall any lectures about this patient population. So during my first year of medical school, I embarked on a mission to educate both my classmates and the faculty about sexual orientation, gender identity, and related health disparities. My fellow classmates and the administration received my efforts warmly; nevertheless, this effort to educate was an incredible challenge for me. Surely other medical school campuses were already discussing the importance of sexuality and gender identity, I thought.

Fast forward to the year 2011. A study in JAMA found that many medical schools fall short in teaching the next generation of physicians about lesbian, gay, bisexual, and transgender (LGBT) health (JAMA. 2011;306[9]:971-7).

Things may have improved for LGBT people, but the world of medicine has yet to catch up. If LGBT medical education is lacking today, imagine how lacking it was for those who went to medical school decades ago. It is my hope that with this new column, we as a medical community can make up for lost time.

Why should physicians, especially pediatricians, care about LGBT health? Although LGBT youth comprise less than 10% of the adolescent population, they have a disproportionate share of health problems compared with their heterosexual peers. LGBT youth are three times as likely to attempt suicide and almost two times as likely to abuse alcohol and drugs compared with heterosexual youth. Among homeless teens in the United States, a whopping 40% are LGBT. HIV still plagues young gay males – especially those of color – and young gay and bisexual women experience an inordinate amount of dating violence from both men and women. Most appalling of all, every 3 days, a transgender person is murdered. These sobering statistics highlight the impact sexual orientation and gender identity have on health.

Why do LGBT youth experience such enormous health problems? A rich body of evidence points to stigma and discrimination as a likely cause. We are familiar with stories of how LGBT youth are kicked out of their homes after coming out to their parents or how male teens suffered bullying for being perceived as “too feminine.” Nonetheless, we tend to ignore the more subtle ways LGBT youth experience stigma and discrimination through our heterosexist language and behavior. Although we could dismiss the phrase “that’s so gay” as just another variation of “that’s so dumb,” an LGBT teen might think “if something is that dumb, then so am I.”

My fellow columnists and I hope that this column will help you get to know a very vulnerable, yet special, population. We will ask you to rethink what you have learned about sexuality and gender. Here, we will start with the basics.

What is the difference between sex and gender?

Sex is the biological distinction between male and female that is determined chromosomally (XX versus XY, although there are variations) and phenotypically, such as organs like the penis or vagina. Gender is a range of characteristics that a culture assigns as typically male and female, which encompasses both anatomy and behaviors. For example, an individual assigned as male because he was born with a penis is also expected to be proactive, a problem solver, stoic, and the breadwinner of the family. Although we’d like to believe that there are clear distinctions between the two solely on the basis of anatomy, we often see many people diverge from behaviors that are typically assigned to a gender. In modern day U.S. society, there are an increasing number of men who stay home to take care of their children – a typically female role. In other words, gender is a spectrum ranging from the very masculine to the very feminine and everything else in between.

What is gender identity?

Gender identity is our own sense of maleness or femaleness. This identity can be based on a variety of factors, including the sex organ one is born with and the culture one is raised in. It also is possible for some people to feel that they do not fit neatly into male or female categories. At the end of the day, only you can determine your gender identity, despite beliefs and attitudes in society about which appearances and behaviors are stereotypically male or female.

Transgender people are individuals who experience a mismatch between their gender identity and their assigned sex at birth. The word “trans” is Latin for “the other side,” highlighting the discrepancy between one’s gender identity and assigned sex. In contrast, people who identify as their assigned sex would be called cisgender. The word “cis” is Latin for “the same side.” A transgender male is someone who was assigned female at birth, but identifies as a male, whereas a transgender female is someone who was assigned male at birth, but identifies as a female. You also may also hear the terms “FTM” (female to male) and “MTF” (male to female) to describe transgender males and females, respectively.

What is sexual orientation?

Sexual orientation refers to our pattern of emotional and/or physical attraction to people who are the same or the opposite gender. The most common in this society is heterosexual, where one finds the opposite gender attractive. Those who identify as gay or lesbian find the same gender attractive. A person who identifies as bisexual finds both genders attractive. There are other sexual orientations that are not as commonly known. Someone who is pansexual is attracted to any sex or gender identity. Asexuals are individuals who don’t find anyone sexually attractive, but could be attracted to someone romantically or emotionally irrespective of sex or gender.

Just as gender is fluid, so is sexuality. Alfred Kinsey, a well-known sexologist, introduced the concept of sexual fluidity with the Kinsey Scale. With this scale, people rate themselves on how attracted they are to each sex, ranging from 0 – meaning exclusively attracted to the opposite sex – to 3 – equally attracted to both sexes – to 6 – exclusively attracted to the same sex. It is possible to move along the spectrum in either direction over time or stay in one place. It is also possible for our sexual identity (i.e. lesbian, gay, bisexual) and sexual behavior (i.e. whom we are having sex with) to not perfectly overlap; attraction is complex. Finally, people often confuse gender identity and sexual orientation. These are two separate concepts and not dependent on each other. For example, someone who was assigned female at birth but now identifies as male can still be attracted to men.

This primer is by no means complete or comprehensive and runs the risk of being oversimplistic. Nevertheless, I hope it will get you thinking about the nature of sexuality and gender identity and how they affect health. In the next couple of months, you will read more on the complexities of sexuality and gender identity, advice on how to talk to your patients about these topics, how to make your clinic a safe place for LGBT youth, the transition process for transgender youth, and much more. I encourage you stick around to learn how you can help this vulnerable, but amazing, group of young people. Until next time …

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh.

Michael Murphy, MD, the co-founder and CEO of ScribeAmerica, talks about the business model that has led to the growing use of medical scribes.

Michael Murphy, MD, the co-founder and CEO of ScribeAmerica, talks about the business model that has led to the growing use of medical scribes.

Michael Murphy, MD, the co-founder and CEO of ScribeAmerica, talks about the business model that has led to the growing use of medical scribes.

Listen to excerpts of Carol Patton’s interview, including Dr. Maki’s explaining the complexities of tandem surfing, his thoughts on the ocean’s spiritual appeal, and he and his wife’s work as intimacy therapists.

http://www.the-hospitalist.org/wp-content/uploads/2015/10/LanceMaki_FINAL-LO-Q_100715.mp3

Listen to excerpts of Carol Patton’s interview, including Dr. Maki’s explaining the complexities of tandem surfing, his thoughts on the ocean’s spiritual appeal, and he and his wife’s work as intimacy therapists.

http://www.the-hospitalist.org/wp-content/uploads/2015/10/LanceMaki_FINAL-LO-Q_100715.mp3

Listen to excerpts of Carol Patton’s interview, including Dr. Maki’s explaining the complexities of tandem surfing, his thoughts on the ocean’s spiritual appeal, and he and his wife’s work as intimacy therapists.

http://www.the-hospitalist.org/wp-content/uploads/2015/10/LanceMaki_FINAL-LO-Q_100715.mp3

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Contrary to popular belief, children with attention-deficit/hyperactivity disorder receiving psychostimulants have a decreased risk of anxiety, according to a meta-analysis by Catherine G. Coughlin and her associates.

Twenty-three studies involving 2,959 ADHD patients were included in the meta-analysis. Children who received methylphenidate derivatives were less likely to experience anxiety, with a relative risk of 0.85, while children receiving amphetamine derivatives had a risk similar to that of those on placebo. Medication acting over a short time also reduced anxiety risk (relative risk, 0.83), compared with long-acting psychostimulants and placebo.

©mik38/thinkstockphotos.com

A higher dosage was found to decrease the risk of anxiety, with the reduction similar for both amphetamine and MPH derivatives. Overall, the relative risk for all children with ADHD taking any psychostimulant was 0.86, compared with that of children receiving a placebo.

“Clinicians should further consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants but significant improvement in ADHD symptoms, as worsening anxiety symptoms are much more likely to be coincidental rather than caused by psychostimulants,” the investigators noted.

Find the study in the Journal of Child and Adolescent Psychopharmacology (doi: 10.1089/cap.2015.0075).

lfranki@frontlinemedcom.com

Contrary to popular belief, children with attention-deficit/hyperactivity disorder receiving psychostimulants have a decreased risk of anxiety, according to a meta-analysis by Catherine G. Coughlin and her associates.

Twenty-three studies involving 2,959 ADHD patients were included in the meta-analysis. Children who received methylphenidate derivatives were less likely to experience anxiety, with a relative risk of 0.85, while children receiving amphetamine derivatives had a risk similar to that of those on placebo. Medication acting over a short time also reduced anxiety risk (relative risk, 0.83), compared with long-acting psychostimulants and placebo.

©mik38/thinkstockphotos.com

A higher dosage was found to decrease the risk of anxiety, with the reduction similar for both amphetamine and MPH derivatives. Overall, the relative risk for all children with ADHD taking any psychostimulant was 0.86, compared with that of children receiving a placebo.

“Clinicians should further consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants but significant improvement in ADHD symptoms, as worsening anxiety symptoms are much more likely to be coincidental rather than caused by psychostimulants,” the investigators noted.

Find the study in the Journal of Child and Adolescent Psychopharmacology (doi: 10.1089/cap.2015.0075).

lfranki@frontlinemedcom.com

Contrary to popular belief, children with attention-deficit/hyperactivity disorder receiving psychostimulants have a decreased risk of anxiety, according to a meta-analysis by Catherine G. Coughlin and her associates.

Twenty-three studies involving 2,959 ADHD patients were included in the meta-analysis. Children who received methylphenidate derivatives were less likely to experience anxiety, with a relative risk of 0.85, while children receiving amphetamine derivatives had a risk similar to that of those on placebo. Medication acting over a short time also reduced anxiety risk (relative risk, 0.83), compared with long-acting psychostimulants and placebo.

©mik38/thinkstockphotos.com

A higher dosage was found to decrease the risk of anxiety, with the reduction similar for both amphetamine and MPH derivatives. Overall, the relative risk for all children with ADHD taking any psychostimulant was 0.86, compared with that of children receiving a placebo.

“Clinicians should further consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants but significant improvement in ADHD symptoms, as worsening anxiety symptoms are much more likely to be coincidental rather than caused by psychostimulants,” the investigators noted.

Find the study in the Journal of Child and Adolescent Psychopharmacology (doi: 10.1089/cap.2015.0075).

lfranki@frontlinemedcom.com

CHICAGO – Carotid artery stenting is safer if patients have been on beta-blockers for at least a month beforehand, according to a review of 5,248 stent cases during 2005-2014.

“Compared to nonusers, patients on long-term beta-blockers are at 34% less risk of stroke and death after carotid artery stenting [odds ratio, 0.66; 95% confidence interval, 0.46-0.95; P = .025], and this risk reduction is amplified to 65% in patients with postop hypertension [OR, 0.35; 95% CI, 0.17-0.73; P = .005].

“Beta-blockers significantly reduce the stroke and death risk ... and should be investigated prospectively for potential use during” carotid artery stenting (CAS), said senior investigator Dr. Mahmoud Malas, director of endovascular surgery and associate professor of surgery at Johns Hopkins Bayview Medical Center in Baltimore.

In the study, long-term beta-blocker use was not associated with postprocedure hypotension in the study. Among patients who developed it, however, beta-blockers were associated with a 48% reduction in the risk of stroke or death at 30 days (OR, 0.52; 95% CI, 0.28-0.98; P = .43).

“We think [the benefits are due to] up-regulation of adrenergic receptors. We think also there is better baroreceptor reflex sensitivity.” Long-term use of beta-blockers reduces heart rate variability, as well, and decreases the risk of hyperperfusion fourfold, Dr. Malas said at the meeting hosted by the Society for Vascular Surgery.

The researchers looked into the issue because they are trying to find a way to make CAS safer in the wake of the Carotid Revascularization Endarterectomy versus Stent Trial (CREST) and others that have shown increased risk compared with carotid endarterectomy.

The subjects were all captured in SVS’s Vascular Quality Initiative database; 2,152 were not on beta-blockers before CAS, 259 were on them for less than 30 days, and 2,837 were on them for more than 30 days.

There were no statistical between-group differences in lesion sites, approach (femoral in almost all the cases), or contrast volume used in surgery, a marker of case complexity.

Long-term users had more diabetes, hypertension, coronary artery disease, and congestive heart failure, whereas short-term users were more symptomatic; those and other differences were controlled for on multivariate analysis.

Aspirin, clopidogrel, and statin use were similar between the groups. About two-thirds of the subjects were men, and the average patientage in the study was about 70 years old.

Overall, the 30-day stroke and death rate was 3.4% (minor stroke 1.5%, major 0.9%, and death 1.2%).

Predictors of postoperative stroke or death at 30 days included symptomatic status, age, diabetes, and perioperative hypotension and hypertension. Prior carotid endarterectomy and distal embolic protection were both protective.

The investigators reported that they had no disclosures.

aotto@frontlinemedcom.com

CHICAGO – Carotid artery stenting is safer if patients have been on beta-blockers for at least a month beforehand, according to a review of 5,248 stent cases during 2005-2014.

“Compared to nonusers, patients on long-term beta-blockers are at 34% less risk of stroke and death after carotid artery stenting [odds ratio, 0.66; 95% confidence interval, 0.46-0.95; P = .025], and this risk reduction is amplified to 65% in patients with postop hypertension [OR, 0.35; 95% CI, 0.17-0.73; P = .005].

“Beta-blockers significantly reduce the stroke and death risk ... and should be investigated prospectively for potential use during” carotid artery stenting (CAS), said senior investigator Dr. Mahmoud Malas, director of endovascular surgery and associate professor of surgery at Johns Hopkins Bayview Medical Center in Baltimore.

In the study, long-term beta-blocker use was not associated with postprocedure hypotension in the study. Among patients who developed it, however, beta-blockers were associated with a 48% reduction in the risk of stroke or death at 30 days (OR, 0.52; 95% CI, 0.28-0.98; P = .43).

“We think [the benefits are due to] up-regulation of adrenergic receptors. We think also there is better baroreceptor reflex sensitivity.” Long-term use of beta-blockers reduces heart rate variability, as well, and decreases the risk of hyperperfusion fourfold, Dr. Malas said at the meeting hosted by the Society for Vascular Surgery.

The researchers looked into the issue because they are trying to find a way to make CAS safer in the wake of the Carotid Revascularization Endarterectomy versus Stent Trial (CREST) and others that have shown increased risk compared with carotid endarterectomy.

The subjects were all captured in SVS’s Vascular Quality Initiative database; 2,152 were not on beta-blockers before CAS, 259 were on them for less than 30 days, and 2,837 were on them for more than 30 days.

There were no statistical between-group differences in lesion sites, approach (femoral in almost all the cases), or contrast volume used in surgery, a marker of case complexity.

Long-term users had more diabetes, hypertension, coronary artery disease, and congestive heart failure, whereas short-term users were more symptomatic; those and other differences were controlled for on multivariate analysis.

Aspirin, clopidogrel, and statin use were similar between the groups. About two-thirds of the subjects were men, and the average patientage in the study was about 70 years old.

Overall, the 30-day stroke and death rate was 3.4% (minor stroke 1.5%, major 0.9%, and death 1.2%).

Predictors of postoperative stroke or death at 30 days included symptomatic status, age, diabetes, and perioperative hypotension and hypertension. Prior carotid endarterectomy and distal embolic protection were both protective.

The investigators reported that they had no disclosures.

aotto@frontlinemedcom.com

CHICAGO – Carotid artery stenting is safer if patients have been on beta-blockers for at least a month beforehand, according to a review of 5,248 stent cases during 2005-2014.

“Compared to nonusers, patients on long-term beta-blockers are at 34% less risk of stroke and death after carotid artery stenting [odds ratio, 0.66; 95% confidence interval, 0.46-0.95; P = .025], and this risk reduction is amplified to 65% in patients with postop hypertension [OR, 0.35; 95% CI, 0.17-0.73; P = .005].

“Beta-blockers significantly reduce the stroke and death risk ... and should be investigated prospectively for potential use during” carotid artery stenting (CAS), said senior investigator Dr. Mahmoud Malas, director of endovascular surgery and associate professor of surgery at Johns Hopkins Bayview Medical Center in Baltimore.

In the study, long-term beta-blocker use was not associated with postprocedure hypotension in the study. Among patients who developed it, however, beta-blockers were associated with a 48% reduction in the risk of stroke or death at 30 days (OR, 0.52; 95% CI, 0.28-0.98; P = .43).

“We think [the benefits are due to] up-regulation of adrenergic receptors. We think also there is better baroreceptor reflex sensitivity.” Long-term use of beta-blockers reduces heart rate variability, as well, and decreases the risk of hyperperfusion fourfold, Dr. Malas said at the meeting hosted by the Society for Vascular Surgery.

The researchers looked into the issue because they are trying to find a way to make CAS safer in the wake of the Carotid Revascularization Endarterectomy versus Stent Trial (CREST) and others that have shown increased risk compared with carotid endarterectomy.

The subjects were all captured in SVS’s Vascular Quality Initiative database; 2,152 were not on beta-blockers before CAS, 259 were on them for less than 30 days, and 2,837 were on them for more than 30 days.

There were no statistical between-group differences in lesion sites, approach (femoral in almost all the cases), or contrast volume used in surgery, a marker of case complexity.

Long-term users had more diabetes, hypertension, coronary artery disease, and congestive heart failure, whereas short-term users were more symptomatic; those and other differences were controlled for on multivariate analysis.

Aspirin, clopidogrel, and statin use were similar between the groups. About two-thirds of the subjects were men, and the average patientage in the study was about 70 years old.

Overall, the 30-day stroke and death rate was 3.4% (minor stroke 1.5%, major 0.9%, and death 1.2%).

Predictors of postoperative stroke or death at 30 days included symptomatic status, age, diabetes, and perioperative hypotension and hypertension. Prior carotid endarterectomy and distal embolic protection were both protective.

The investigators reported that they had no disclosures.

aotto@frontlinemedcom.com

SAN DIEGO – In-hospital mortality in patients with aspergillosis plummeted nationally, according to data from 2001-2011, with the biggest improvement seen in immunocompromised patients traditionally considered at high mortality risk, Dr. Masako Mizusawa reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The decline in in-hospital mortality wasn’t linear. Rather, it followed a stepwise pattern, and those steps occurred in association with three major advances during the study years: Food and Drug Administration approval of voriconazole in 2002, the FDA’s 2003 approval of the galactomannan serologic assay allowing for speedier diagnosis of aspergillosis, and the 2008 Infectious Diseases Society of America clinical practice guidelines on the treatment of aspergillosis (Clin Infect Dis. 2008 Feb 1;46[3]:327-60).

Bruce Jancin/Frontline Medical News

“This was an observational study and we can’t actually say that these events are causative. But just looking at the time relationship, it certainly looks plausible,” Dr. Mizusawa said.

In addition, the median hospital length of stay decreased from 9 to 7 days in patients with this potentially life-threatening infection, noted Dr. Mizusawa of Tufts Medical Center, Boston.

She presented what she believes is the largest U.S. longitudinal study of hospital care for aspergillosis. The retrospective study used nationally representative data from the Agency for Healthcare Research and Quality’s Healthcare Utilization and Cost Project–Nationwide Inpatient Sample.

Dr. Mizusawa and coinvestigators defined aspergillosis patients as being at high mortality risk if they had established risk factors indicative of immunocompromise, including hematologic malignancy, neutropenia, recent stem cell or solid organ transplantation, HIV, or rheumatologic disease. Patients at lower mortality risk included those with asthma, COPD, diabetes, malnutrition, pulmonary tuberculosis, or non-TB mycobacterial infection.

The proportion of patients who were high risk climbed over the years, from 41% among the 892 patients with aspergillosis-related hospitalization in the 2001 sample to 50% among 1,420 patients in 2011. Yet in-hospital mortality in high-risk patients fell from 26.4% in 2001 to 9.1% in 2011. Meanwhile, the mortality rate in lower-risk patients improved from 14.6% to 6.6%. The overall in-hospital mortality rate went from 18.8% to 7.7%.

Of note, the proportion of aspergillosis patients with renal failure jumped from 9.8% in 2001 to 21.5% in 2011, even though the treatments for aspergillosis are relatively non-nephrotoxic, with the exception of amphotericin B. The outlook for these patients has improved greatly: In-hospital mortality for aspergillosis patients in renal failure went from 40.2% in 2001 to 16.1% in 2011.

While in-hospital mortality and length of stay were decreasing during the study years, total hospital charges for patients with aspergillosis were going up: from a median of $29,998 in 2001 to $44,888 in 2001 dollars a decade later. This cost-of-care increase was confined to patients at lower baseline risk or with no risk factors. Somewhat surprisingly, the high-risk group didn’t have a significant increase in hospital charges over the 10-year period.

“Maybe we’re just doing a better job of treating them, so they may not necessarily have to use a lot of resources,” Dr. Mizusawa offered as explanation.

She reported having no financial conflicts regarding this unfunded study.

bjancin@frontlinemedcom.com

SAN DIEGO – In-hospital mortality in patients with aspergillosis plummeted nationally, according to data from 2001-2011, with the biggest improvement seen in immunocompromised patients traditionally considered at high mortality risk, Dr. Masako Mizusawa reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The decline in in-hospital mortality wasn’t linear. Rather, it followed a stepwise pattern, and those steps occurred in association with three major advances during the study years: Food and Drug Administration approval of voriconazole in 2002, the FDA’s 2003 approval of the galactomannan serologic assay allowing for speedier diagnosis of aspergillosis, and the 2008 Infectious Diseases Society of America clinical practice guidelines on the treatment of aspergillosis (Clin Infect Dis. 2008 Feb 1;46[3]:327-60).

Bruce Jancin/Frontline Medical News

“This was an observational study and we can’t actually say that these events are causative. But just looking at the time relationship, it certainly looks plausible,” Dr. Mizusawa said.

In addition, the median hospital length of stay decreased from 9 to 7 days in patients with this potentially life-threatening infection, noted Dr. Mizusawa of Tufts Medical Center, Boston.

She presented what she believes is the largest U.S. longitudinal study of hospital care for aspergillosis. The retrospective study used nationally representative data from the Agency for Healthcare Research and Quality’s Healthcare Utilization and Cost Project–Nationwide Inpatient Sample.

Dr. Mizusawa and coinvestigators defined aspergillosis patients as being at high mortality risk if they had established risk factors indicative of immunocompromise, including hematologic malignancy, neutropenia, recent stem cell or solid organ transplantation, HIV, or rheumatologic disease. Patients at lower mortality risk included those with asthma, COPD, diabetes, malnutrition, pulmonary tuberculosis, or non-TB mycobacterial infection.

The proportion of patients who were high risk climbed over the years, from 41% among the 892 patients with aspergillosis-related hospitalization in the 2001 sample to 50% among 1,420 patients in 2011. Yet in-hospital mortality in high-risk patients fell from 26.4% in 2001 to 9.1% in 2011. Meanwhile, the mortality rate in lower-risk patients improved from 14.6% to 6.6%. The overall in-hospital mortality rate went from 18.8% to 7.7%.

Of note, the proportion of aspergillosis patients with renal failure jumped from 9.8% in 2001 to 21.5% in 2011, even though the treatments for aspergillosis are relatively non-nephrotoxic, with the exception of amphotericin B. The outlook for these patients has improved greatly: In-hospital mortality for aspergillosis patients in renal failure went from 40.2% in 2001 to 16.1% in 2011.

While in-hospital mortality and length of stay were decreasing during the study years, total hospital charges for patients with aspergillosis were going up: from a median of $29,998 in 2001 to $44,888 in 2001 dollars a decade later. This cost-of-care increase was confined to patients at lower baseline risk or with no risk factors. Somewhat surprisingly, the high-risk group didn’t have a significant increase in hospital charges over the 10-year period.

“Maybe we’re just doing a better job of treating them, so they may not necessarily have to use a lot of resources,” Dr. Mizusawa offered as explanation.

She reported having no financial conflicts regarding this unfunded study.

bjancin@frontlinemedcom.com

SAN DIEGO – In-hospital mortality in patients with aspergillosis plummeted nationally, according to data from 2001-2011, with the biggest improvement seen in immunocompromised patients traditionally considered at high mortality risk, Dr. Masako Mizusawa reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The decline in in-hospital mortality wasn’t linear. Rather, it followed a stepwise pattern, and those steps occurred in association with three major advances during the study years: Food and Drug Administration approval of voriconazole in 2002, the FDA’s 2003 approval of the galactomannan serologic assay allowing for speedier diagnosis of aspergillosis, and the 2008 Infectious Diseases Society of America clinical practice guidelines on the treatment of aspergillosis (Clin Infect Dis. 2008 Feb 1;46[3]:327-60).

Bruce Jancin/Frontline Medical News

“This was an observational study and we can’t actually say that these events are causative. But just looking at the time relationship, it certainly looks plausible,” Dr. Mizusawa said.

In addition, the median hospital length of stay decreased from 9 to 7 days in patients with this potentially life-threatening infection, noted Dr. Mizusawa of Tufts Medical Center, Boston.

She presented what she believes is the largest U.S. longitudinal study of hospital care for aspergillosis. The retrospective study used nationally representative data from the Agency for Healthcare Research and Quality’s Healthcare Utilization and Cost Project–Nationwide Inpatient Sample.

Dr. Mizusawa and coinvestigators defined aspergillosis patients as being at high mortality risk if they had established risk factors indicative of immunocompromise, including hematologic malignancy, neutropenia, recent stem cell or solid organ transplantation, HIV, or rheumatologic disease. Patients at lower mortality risk included those with asthma, COPD, diabetes, malnutrition, pulmonary tuberculosis, or non-TB mycobacterial infection.

The proportion of patients who were high risk climbed over the years, from 41% among the 892 patients with aspergillosis-related hospitalization in the 2001 sample to 50% among 1,420 patients in 2011. Yet in-hospital mortality in high-risk patients fell from 26.4% in 2001 to 9.1% in 2011. Meanwhile, the mortality rate in lower-risk patients improved from 14.6% to 6.6%. The overall in-hospital mortality rate went from 18.8% to 7.7%.

Of note, the proportion of aspergillosis patients with renal failure jumped from 9.8% in 2001 to 21.5% in 2011, even though the treatments for aspergillosis are relatively non-nephrotoxic, with the exception of amphotericin B. The outlook for these patients has improved greatly: In-hospital mortality for aspergillosis patients in renal failure went from 40.2% in 2001 to 16.1% in 2011.

While in-hospital mortality and length of stay were decreasing during the study years, total hospital charges for patients with aspergillosis were going up: from a median of $29,998 in 2001 to $44,888 in 2001 dollars a decade later. This cost-of-care increase was confined to patients at lower baseline risk or with no risk factors. Somewhat surprisingly, the high-risk group didn’t have a significant increase in hospital charges over the 10-year period.

“Maybe we’re just doing a better job of treating them, so they may not necessarily have to use a lot of resources,” Dr. Mizusawa offered as explanation.

She reported having no financial conflicts regarding this unfunded study.

bjancin@frontlinemedcom.com

HSCT preparation

Photo by Chad McNeeley

A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)

can be roughly as safe and effective as a fully matched HSCT.

The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.

Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.

However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.

Researchers reported these results in Biology of Blood and Marrow Transplantation.

“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.

“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”

With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.

The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).

The 2-step protocol

All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 10⁸ cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.

Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.

On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m²) starting on day +1.

In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.

Results

The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).

Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).

The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).

The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001).  But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).

The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).

The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).

There were no deaths from infections or GVHD in either group.

“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.

“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”

HSCT preparation

Photo by Chad McNeeley

A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)

can be roughly as safe and effective as a fully matched HSCT.

The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.

Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.

However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.

Researchers reported these results in Biology of Blood and Marrow Transplantation.

“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.

“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”

With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.

The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).

The 2-step protocol

All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 10⁸ cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.

Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.

On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m²) starting on day +1.

In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.

Results

The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).

Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).

The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).

The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001).  But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).

The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).

The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).

There were no deaths from infections or GVHD in either group.

“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.

“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”

HSCT preparation

Photo by Chad McNeeley

A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)

can be roughly as safe and effective as a fully matched HSCT.

The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.

Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.

However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.

Researchers reported these results in Biology of Blood and Marrow Transplantation.

“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.

“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”

With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.

The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).

The 2-step protocol

All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 10⁸ cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.

Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.

On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m²) starting on day +1.

In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.

Results

The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).

Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).

The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).

The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001).  But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).

The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).

The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).

There were no deaths from infections or GVHD in either group.

“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.

“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”

Micrograph showing CTCL

High-throughput sequencing (HTS) may enable earlier diagnosis of cutaneous T-cell lymphoma (CTCL), according to a study published in Science Translational Medicine.

Researchers said HTS, which provided new insights into the biology of CTCL, accurately diagnosed 100% of patients with the disease, including those with early stage and recurrent CTCL.

HTS exhibited greater sensitivity and specificity than polymerase chain reaction.

The researchers noted that, in CTCL, cancerous T cells accumulate in the skin, causing skin tumors but also rashes that are often mistaken for benign inflammatory skin conditions. And this delays diagnosis.

“Using current methods, it takes, on average, 6 years for patients to receive a definitive CTCL diagnosis,” said Rachael Clark, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“As a result, appropriate therapy is delayed, often until the disease worsens to the point where diagnosis is clear, but effective treatment is more difficult.”

In search of a new diagnostic approach, Dr Clark and her colleagues used HTS to analyze T-cell receptor genes from blood and skin tissue samples. The team compared samples from 46 CTCL patients to samples from healthy individuals and patients with psoriasis, eczema, and other non-cancerous, inflammatory skin diseases.

By identifying and quantifying malignant T cells, HTS accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction correctly identified 70% of the CTCL samples, often missing earlier-stage tumors.

For a subset of patients, the researchers used HTS to track malignant T cells over time, allowing them to detect early recurrence and monitor patient response to treatment.

HTS also revealed new insights into the cell of origin for CTCL, which has remained unresolved. The researchers found that CTCL arises from mature T cells, a discovery that may aid the development of more effective therapy.

The team said that, altogether, their findings suggest HTS is a promising tool for guiding earlier diagnosis and, thus, treatment of CTCL patients.

HTS was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.

Micrograph showing CTCL

High-throughput sequencing (HTS) may enable earlier diagnosis of cutaneous T-cell lymphoma (CTCL), according to a study published in Science Translational Medicine.

Researchers said HTS, which provided new insights into the biology of CTCL, accurately diagnosed 100% of patients with the disease, including those with early stage and recurrent CTCL.

HTS exhibited greater sensitivity and specificity than polymerase chain reaction.

The researchers noted that, in CTCL, cancerous T cells accumulate in the skin, causing skin tumors but also rashes that are often mistaken for benign inflammatory skin conditions. And this delays diagnosis.

“Using current methods, it takes, on average, 6 years for patients to receive a definitive CTCL diagnosis,” said Rachael Clark, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“As a result, appropriate therapy is delayed, often until the disease worsens to the point where diagnosis is clear, but effective treatment is more difficult.”

In search of a new diagnostic approach, Dr Clark and her colleagues used HTS to analyze T-cell receptor genes from blood and skin tissue samples. The team compared samples from 46 CTCL patients to samples from healthy individuals and patients with psoriasis, eczema, and other non-cancerous, inflammatory skin diseases.

By identifying and quantifying malignant T cells, HTS accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction correctly identified 70% of the CTCL samples, often missing earlier-stage tumors.

For a subset of patients, the researchers used HTS to track malignant T cells over time, allowing them to detect early recurrence and monitor patient response to treatment.

HTS also revealed new insights into the cell of origin for CTCL, which has remained unresolved. The researchers found that CTCL arises from mature T cells, a discovery that may aid the development of more effective therapy.

The team said that, altogether, their findings suggest HTS is a promising tool for guiding earlier diagnosis and, thus, treatment of CTCL patients.

HTS was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.

Micrograph showing CTCL

High-throughput sequencing (HTS) may enable earlier diagnosis of cutaneous T-cell lymphoma (CTCL), according to a study published in Science Translational Medicine.

Researchers said HTS, which provided new insights into the biology of CTCL, accurately diagnosed 100% of patients with the disease, including those with early stage and recurrent CTCL.

HTS exhibited greater sensitivity and specificity than polymerase chain reaction.

The researchers noted that, in CTCL, cancerous T cells accumulate in the skin, causing skin tumors but also rashes that are often mistaken for benign inflammatory skin conditions. And this delays diagnosis.

“Using current methods, it takes, on average, 6 years for patients to receive a definitive CTCL diagnosis,” said Rachael Clark, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“As a result, appropriate therapy is delayed, often until the disease worsens to the point where diagnosis is clear, but effective treatment is more difficult.”

In search of a new diagnostic approach, Dr Clark and her colleagues used HTS to analyze T-cell receptor genes from blood and skin tissue samples. The team compared samples from 46 CTCL patients to samples from healthy individuals and patients with psoriasis, eczema, and other non-cancerous, inflammatory skin diseases.

By identifying and quantifying malignant T cells, HTS accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction correctly identified 70% of the CTCL samples, often missing earlier-stage tumors.

For a subset of patients, the researchers used HTS to track malignant T cells over time, allowing them to detect early recurrence and monitor patient response to treatment.

HTS also revealed new insights into the cell of origin for CTCL, which has remained unresolved. The researchers found that CTCL arises from mature T cells, a discovery that may aid the development of more effective therapy.

The team said that, altogether, their findings suggest HTS is a promising tool for guiding earlier diagnosis and, thus, treatment of CTCL patients.

HTS was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.