Looking for in-person board review prep? Join us in Orlando, August 18 to 27, for the best live review of pulmonary, critical care, and sleep medicine.

Looking for in-person board review prep? Join us in Orlando, August 18 to 27, for the best live review of pulmonary, critical care, and sleep medicine.

Looking for in-person board review prep? Join us in Orlando, August 18 to 27, for the best live review of pulmonary, critical care, and sleep medicine.

Fitusiran appears to promote hemostasis and reduce the frequency of bleeding in patients with hemophilia. In a phase I trial of the investigational agent, breakthrough bleeds were treated effectively and safely with replacement factor or bypassing agent.

Bleed events were rare among patients achieving target antithrombin lowering of greater than 75% on fitusiran. Those that did occur were treated with factor concentrates, including recombinant Factor VIII or recombinant Factor IX, or with bypassing agents, including recombinant Factor VIIa or activated prothrombin complex–concentrates, Savita Rangarajan, MD, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.

The study included 41 patients with hemophilia A or B – 25 patients with inhibitors and 16 without inhibitors – who received either 50 mg or 80 mg of fitusiran. Early multiple ascending dose–cohorts received weekly subcutaneous dosing, and later cohorts received monthly dosing. All patients tolerated treatment well, with no serious adverse events related to the study drug. No thromboembolic events occurred, and the majority of adverse events were mild or moderate in severity, she noted.

Among patients with inhibitors, eight bleeds occurred in five patients with hemophilia A who were treated with Factor VIII, and three bleeds occurred in two patients with hemophilia B who were treated with Factor IX. Among those without inhibitors, six bleeds occurred in three patients treated with activated prothrombin complex–concentrates, and four occurred in three patients treated with recombinant Factor VIIa, said Dr. Rangarajan of Hampshire Hospitals NHS Foundation Trust, Basingstoke, England.

The ranges of factor replacement used per injection were 7-32 IU/kg of Factor VIII and 7-43 IU/kg of Factor IX.

The ranges of bypassing agents used per injection were 14-75 U/kg of activated prothrombin complex–concentrates (mean, 2.2 administrations per bleed) and 93-133 μg/kg of recombinant Factor VIIa (mean, 1.5 administrations per bleed), she said.

Doses of the factor concentrates and bypassing agents used were at or below those recommended by the World Federation of Hemophilia.

This phase I study of fitusiran, which targets and lowers antithrombin to improve thrombin generation and promote hemostasis in patients with hemophilia, is being conducted in four parts: Part A with healthy volunteers, parts B and C with patients with moderate to severe hemophilia A or B, and part D with patients with hemophilia A or B with inhibitors.

Findings from the current exploratory analysis of the data are encouraging as they demonstrate good treatment effect in the absence of identified safety concerns, Dr. Rangarajan said, noting that fitusiran should advance to pivotal studies in 2017 and that data on bleed management from a phase I and phase II open label extension will guide protocol on bleed management in phase III.

Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.

[email protected]

Fitusiran appears to promote hemostasis and reduce the frequency of bleeding in patients with hemophilia. In a phase I trial of the investigational agent, breakthrough bleeds were treated effectively and safely with replacement factor or bypassing agent.

Bleed events were rare among patients achieving target antithrombin lowering of greater than 75% on fitusiran. Those that did occur were treated with factor concentrates, including recombinant Factor VIII or recombinant Factor IX, or with bypassing agents, including recombinant Factor VIIa or activated prothrombin complex–concentrates, Savita Rangarajan, MD, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.

The study included 41 patients with hemophilia A or B – 25 patients with inhibitors and 16 without inhibitors – who received either 50 mg or 80 mg of fitusiran. Early multiple ascending dose–cohorts received weekly subcutaneous dosing, and later cohorts received monthly dosing. All patients tolerated treatment well, with no serious adverse events related to the study drug. No thromboembolic events occurred, and the majority of adverse events were mild or moderate in severity, she noted.

Among patients with inhibitors, eight bleeds occurred in five patients with hemophilia A who were treated with Factor VIII, and three bleeds occurred in two patients with hemophilia B who were treated with Factor IX. Among those without inhibitors, six bleeds occurred in three patients treated with activated prothrombin complex–concentrates, and four occurred in three patients treated with recombinant Factor VIIa, said Dr. Rangarajan of Hampshire Hospitals NHS Foundation Trust, Basingstoke, England.

The ranges of factor replacement used per injection were 7-32 IU/kg of Factor VIII and 7-43 IU/kg of Factor IX.

The ranges of bypassing agents used per injection were 14-75 U/kg of activated prothrombin complex–concentrates (mean, 2.2 administrations per bleed) and 93-133 μg/kg of recombinant Factor VIIa (mean, 1.5 administrations per bleed), she said.

Doses of the factor concentrates and bypassing agents used were at or below those recommended by the World Federation of Hemophilia.

This phase I study of fitusiran, which targets and lowers antithrombin to improve thrombin generation and promote hemostasis in patients with hemophilia, is being conducted in four parts: Part A with healthy volunteers, parts B and C with patients with moderate to severe hemophilia A or B, and part D with patients with hemophilia A or B with inhibitors.

Findings from the current exploratory analysis of the data are encouraging as they demonstrate good treatment effect in the absence of identified safety concerns, Dr. Rangarajan said, noting that fitusiran should advance to pivotal studies in 2017 and that data on bleed management from a phase I and phase II open label extension will guide protocol on bleed management in phase III.

Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.

[email protected]

Fitusiran appears to promote hemostasis and reduce the frequency of bleeding in patients with hemophilia. In a phase I trial of the investigational agent, breakthrough bleeds were treated effectively and safely with replacement factor or bypassing agent.

Bleed events were rare among patients achieving target antithrombin lowering of greater than 75% on fitusiran. Those that did occur were treated with factor concentrates, including recombinant Factor VIII or recombinant Factor IX, or with bypassing agents, including recombinant Factor VIIa or activated prothrombin complex–concentrates, Savita Rangarajan, MD, reported at the annual meeting of the European Association for Haemophilia and Allied Disorders.

The study included 41 patients with hemophilia A or B – 25 patients with inhibitors and 16 without inhibitors – who received either 50 mg or 80 mg of fitusiran. Early multiple ascending dose–cohorts received weekly subcutaneous dosing, and later cohorts received monthly dosing. All patients tolerated treatment well, with no serious adverse events related to the study drug. No thromboembolic events occurred, and the majority of adverse events were mild or moderate in severity, she noted.

Among patients with inhibitors, eight bleeds occurred in five patients with hemophilia A who were treated with Factor VIII, and three bleeds occurred in two patients with hemophilia B who were treated with Factor IX. Among those without inhibitors, six bleeds occurred in three patients treated with activated prothrombin complex–concentrates, and four occurred in three patients treated with recombinant Factor VIIa, said Dr. Rangarajan of Hampshire Hospitals NHS Foundation Trust, Basingstoke, England.

The ranges of factor replacement used per injection were 7-32 IU/kg of Factor VIII and 7-43 IU/kg of Factor IX.

The ranges of bypassing agents used per injection were 14-75 U/kg of activated prothrombin complex–concentrates (mean, 2.2 administrations per bleed) and 93-133 μg/kg of recombinant Factor VIIa (mean, 1.5 administrations per bleed), she said.

Doses of the factor concentrates and bypassing agents used were at or below those recommended by the World Federation of Hemophilia.

This phase I study of fitusiran, which targets and lowers antithrombin to improve thrombin generation and promote hemostasis in patients with hemophilia, is being conducted in four parts: Part A with healthy volunteers, parts B and C with patients with moderate to severe hemophilia A or B, and part D with patients with hemophilia A or B with inhibitors.

Findings from the current exploratory analysis of the data are encouraging as they demonstrate good treatment effect in the absence of identified safety concerns, Dr. Rangarajan said, noting that fitusiran should advance to pivotal studies in 2017 and that data on bleed management from a phase I and phase II open label extension will guide protocol on bleed management in phase III.

Dr. Rangarajan has received grant or research support from Alnylam Pharmaceuticals, BioMarin Pharmaceutical, Novo Nordisk, Pfizer, and Shire.

[email protected]

National Harbor, MD. – The PARP inhibitor rucaparib is safe and effective in patients with primary platinum-sensitive high-grade ovarian carcinoma who have germline or somatic BRCA mutations, according to integrated summary data from parts 1 and 2 of the phase II ARIEL2 study.

Prior analyses of ARIEL2 data included 493 patients with germline/somatic BRCA mutations and BRCA wild-type. The current analysis included the 41 patients from ARIEL2 part 1 and the 93 patients from ARIEL2 part 2 who had germline or somatic BRCA mutations, and overall response rates in these patients ranged from 52% to 86% depending on the number of prior therapies, Gottfried E. Konecny, MD, reported at the annual meeting of the Society of Gynecologic Oncology.

The highest overall response rates were seen in platinum-sensitive vs. platinum-resistant and platinum-refractory patients, said Dr. Konecny of the University of California, Los Angeles.

Median progression-free survival was 12.7 months in the platinum-sensitive patients vs. 7.3 and 5.0 months in platinum-resistant and platinum-refractory patients, respectively, he said.

Treatment was generally safe and well tolerated. The most common treatment-emergent adverse events were nausea, fatigue, vomiting, and anemia; the most common grade 3/4 events included anemia, increased ALT/AST, and fatigue.

Previous findings from ARIEL2 and other studies of rucaparib led to conditional approval of the drug (pending further confirmation of the data), first for patients with germline or somatic BRCA mutations who fail at least three prior lines of chemotherapy, then for those who fail two or more prior therapies.

In this video, Dr. Konecny discusses his findings and the next steps with respect to the study of rucaparib for high-grade ovarian carcinoma.

ARIEL2 was supported by Clovis Oncology. Dr. Konecny is on the speakers’ bureau for AstraZeneca and Clovis Oncology and has received research funding or honorarium from Amgen, Merck, and Novartis.

[email protected]

National Harbor, MD. – The PARP inhibitor rucaparib is safe and effective in patients with primary platinum-sensitive high-grade ovarian carcinoma who have germline or somatic BRCA mutations, according to integrated summary data from parts 1 and 2 of the phase II ARIEL2 study.

Prior analyses of ARIEL2 data included 493 patients with germline/somatic BRCA mutations and BRCA wild-type. The current analysis included the 41 patients from ARIEL2 part 1 and the 93 patients from ARIEL2 part 2 who had germline or somatic BRCA mutations, and overall response rates in these patients ranged from 52% to 86% depending on the number of prior therapies, Gottfried E. Konecny, MD, reported at the annual meeting of the Society of Gynecologic Oncology.

The highest overall response rates were seen in platinum-sensitive vs. platinum-resistant and platinum-refractory patients, said Dr. Konecny of the University of California, Los Angeles.

Median progression-free survival was 12.7 months in the platinum-sensitive patients vs. 7.3 and 5.0 months in platinum-resistant and platinum-refractory patients, respectively, he said.

Treatment was generally safe and well tolerated. The most common treatment-emergent adverse events were nausea, fatigue, vomiting, and anemia; the most common grade 3/4 events included anemia, increased ALT/AST, and fatigue.

Previous findings from ARIEL2 and other studies of rucaparib led to conditional approval of the drug (pending further confirmation of the data), first for patients with germline or somatic BRCA mutations who fail at least three prior lines of chemotherapy, then for those who fail two or more prior therapies.

In this video, Dr. Konecny discusses his findings and the next steps with respect to the study of rucaparib for high-grade ovarian carcinoma.

ARIEL2 was supported by Clovis Oncology. Dr. Konecny is on the speakers’ bureau for AstraZeneca and Clovis Oncology and has received research funding or honorarium from Amgen, Merck, and Novartis.

[email protected]

National Harbor, MD. – The PARP inhibitor rucaparib is safe and effective in patients with primary platinum-sensitive high-grade ovarian carcinoma who have germline or somatic BRCA mutations, according to integrated summary data from parts 1 and 2 of the phase II ARIEL2 study.

Prior analyses of ARIEL2 data included 493 patients with germline/somatic BRCA mutations and BRCA wild-type. The current analysis included the 41 patients from ARIEL2 part 1 and the 93 patients from ARIEL2 part 2 who had germline or somatic BRCA mutations, and overall response rates in these patients ranged from 52% to 86% depending on the number of prior therapies, Gottfried E. Konecny, MD, reported at the annual meeting of the Society of Gynecologic Oncology.

The highest overall response rates were seen in platinum-sensitive vs. platinum-resistant and platinum-refractory patients, said Dr. Konecny of the University of California, Los Angeles.

Median progression-free survival was 12.7 months in the platinum-sensitive patients vs. 7.3 and 5.0 months in platinum-resistant and platinum-refractory patients, respectively, he said.

Treatment was generally safe and well tolerated. The most common treatment-emergent adverse events were nausea, fatigue, vomiting, and anemia; the most common grade 3/4 events included anemia, increased ALT/AST, and fatigue.

Previous findings from ARIEL2 and other studies of rucaparib led to conditional approval of the drug (pending further confirmation of the data), first for patients with germline or somatic BRCA mutations who fail at least three prior lines of chemotherapy, then for those who fail two or more prior therapies.

In this video, Dr. Konecny discusses his findings and the next steps with respect to the study of rucaparib for high-grade ovarian carcinoma.

ARIEL2 was supported by Clovis Oncology. Dr. Konecny is on the speakers’ bureau for AstraZeneca and Clovis Oncology and has received research funding or honorarium from Amgen, Merck, and Novartis.

[email protected]

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An individual’s identity is a learned response to social stimuli, modeling oneself to the expectations of others. Doctors are perceived to be benevolent, knowledgeable, and powerful in matters of life and death. However, a complex concept of reverse hierarchy and role disorientation can take place when a doctor becomes a patient. Because doctors dedicate much of their lives to ensuring the well-being of patients, they may have a skewed perception of their personal health risks and fail to acknowledge that they, too, can fall victim to illness. 

‘Them, not me’

Studies have found that doctors often do not advocate the same treatments for themselves than they would for their patients:

• Although most doctors recommend annual check-ups for their patients, 70% of physicians do not get one themselves.¹ 
• Doctors are more likely to recommend potentially life-saving treatment with severe side effects to their patients than for themselves.²

These studies highlight how objectivity may be absent when doctors make decisions about their own treatment, as well as the complexity associated with treating a doctor as a patient.

A doctor’s sense of identity often is strongest in a health care setting. However, becoming a patient precipitates a drastic change in authority, duty, privacy, and even attire. Earlier this year, a colleague was in the hospital for workup of a cluster of symptoms. On a personal level, she experienced a momentary loss of identity, increased anxiety, and loss of self-esteem, which reduced her ability to connect with those who, in her professional role as “doctor,” were her colleagues. Trust became a matter of contention, especially in the context of understanding the inner workings of the health care system—its limitations, risks, and the possibility of human error. Professionally, she thought some management procedures were objectionable, but quickly assumed the passive role to avoid being labeled as “difficult.”

My colleague relayed 2 interesting viewpoints. First, doctors’ detached communication style seemed to evaporate when she revealed that she also is a physician. Perhaps it was the feeling of pride or competition that comes with being responsible for a colleague’s welfare or the camaraderie that lessened the divide. Slowness to relay clinical information or disregard for transparency—sometimes seen in the inpatient setting—were not apparent during my colleague’s care. However, aspects considered trivial from a doctor’s point of view, such as pre-procedural fasting, lack of privacy, and room changes became acutely intrusive.

Second, my colleague observed that her treatment team was overly solicitous. They wanted her to be pain-free and organized “urgent” tests to minimize waiting time. She recognized that there was an overt obligation to procure excessive investigations and treatment compared with a usual patient, because there was wariness of her vigilance of when things go wrong or are overlooked.

This situation was a reminder that clinicians should be mindful of finding the middle ground between unnecessary treatment for a “doctor as patient” and uninformed treatment for a “standard patient.”

Seek to understand

Role reversal represents the fundamental skill of connecting with others through self-awareness, self-regulation, and empathy.³ Studies have found that doctors who have assumed the patient role show more empathy and possess better communication skills.⁴ The situation for the doctor who becomes a patient may be disconcerting, but the “do no harm” nature of medicine and the generally accepting demeanor of patients render the relationship between empathy and role reversal especially harmonious. Although it is comfortable and convenient to stay on one side of the relationship, grasping an emotional representation of the other side is essential. It is the process of overcoming egocentricity and perceiving the subjective experience of the other role that is rewarding. We all desire to be understood, but to be understood, we must first seek to understand.

An individual’s identity is a learned response to social stimuli, modeling oneself to the expectations of others. Doctors are perceived to be benevolent, knowledgeable, and powerful in matters of life and death. However, a complex concept of reverse hierarchy and role disorientation can take place when a doctor becomes a patient. Because doctors dedicate much of their lives to ensuring the well-being of patients, they may have a skewed perception of their personal health risks and fail to acknowledge that they, too, can fall victim to illness. 

‘Them, not me’

Studies have found that doctors often do not advocate the same treatments for themselves than they would for their patients:

• Although most doctors recommend annual check-ups for their patients, 70% of physicians do not get one themselves.¹ 
• Doctors are more likely to recommend potentially life-saving treatment with severe side effects to their patients than for themselves.²

These studies highlight how objectivity may be absent when doctors make decisions about their own treatment, as well as the complexity associated with treating a doctor as a patient.

A doctor’s sense of identity often is strongest in a health care setting. However, becoming a patient precipitates a drastic change in authority, duty, privacy, and even attire. Earlier this year, a colleague was in the hospital for workup of a cluster of symptoms. On a personal level, she experienced a momentary loss of identity, increased anxiety, and loss of self-esteem, which reduced her ability to connect with those who, in her professional role as “doctor,” were her colleagues. Trust became a matter of contention, especially in the context of understanding the inner workings of the health care system—its limitations, risks, and the possibility of human error. Professionally, she thought some management procedures were objectionable, but quickly assumed the passive role to avoid being labeled as “difficult.”

My colleague relayed 2 interesting viewpoints. First, doctors’ detached communication style seemed to evaporate when she revealed that she also is a physician. Perhaps it was the feeling of pride or competition that comes with being responsible for a colleague’s welfare or the camaraderie that lessened the divide. Slowness to relay clinical information or disregard for transparency—sometimes seen in the inpatient setting—were not apparent during my colleague’s care. However, aspects considered trivial from a doctor’s point of view, such as pre-procedural fasting, lack of privacy, and room changes became acutely intrusive.

Second, my colleague observed that her treatment team was overly solicitous. They wanted her to be pain-free and organized “urgent” tests to minimize waiting time. She recognized that there was an overt obligation to procure excessive investigations and treatment compared with a usual patient, because there was wariness of her vigilance of when things go wrong or are overlooked.

This situation was a reminder that clinicians should be mindful of finding the middle ground between unnecessary treatment for a “doctor as patient” and uninformed treatment for a “standard patient.”

Seek to understand

Role reversal represents the fundamental skill of connecting with others through self-awareness, self-regulation, and empathy.³ Studies have found that doctors who have assumed the patient role show more empathy and possess better communication skills.⁴ The situation for the doctor who becomes a patient may be disconcerting, but the “do no harm” nature of medicine and the generally accepting demeanor of patients render the relationship between empathy and role reversal especially harmonious. Although it is comfortable and convenient to stay on one side of the relationship, grasping an emotional representation of the other side is essential. It is the process of overcoming egocentricity and perceiving the subjective experience of the other role that is rewarding. We all desire to be understood, but to be understood, we must first seek to understand.

An individual’s identity is a learned response to social stimuli, modeling oneself to the expectations of others. Doctors are perceived to be benevolent, knowledgeable, and powerful in matters of life and death. However, a complex concept of reverse hierarchy and role disorientation can take place when a doctor becomes a patient. Because doctors dedicate much of their lives to ensuring the well-being of patients, they may have a skewed perception of their personal health risks and fail to acknowledge that they, too, can fall victim to illness. 

‘Them, not me’

Studies have found that doctors often do not advocate the same treatments for themselves than they would for their patients:

• Although most doctors recommend annual check-ups for their patients, 70% of physicians do not get one themselves.¹ 
• Doctors are more likely to recommend potentially life-saving treatment with severe side effects to their patients than for themselves.²

These studies highlight how objectivity may be absent when doctors make decisions about their own treatment, as well as the complexity associated with treating a doctor as a patient.

A doctor’s sense of identity often is strongest in a health care setting. However, becoming a patient precipitates a drastic change in authority, duty, privacy, and even attire. Earlier this year, a colleague was in the hospital for workup of a cluster of symptoms. On a personal level, she experienced a momentary loss of identity, increased anxiety, and loss of self-esteem, which reduced her ability to connect with those who, in her professional role as “doctor,” were her colleagues. Trust became a matter of contention, especially in the context of understanding the inner workings of the health care system—its limitations, risks, and the possibility of human error. Professionally, she thought some management procedures were objectionable, but quickly assumed the passive role to avoid being labeled as “difficult.”

My colleague relayed 2 interesting viewpoints. First, doctors’ detached communication style seemed to evaporate when she revealed that she also is a physician. Perhaps it was the feeling of pride or competition that comes with being responsible for a colleague’s welfare or the camaraderie that lessened the divide. Slowness to relay clinical information or disregard for transparency—sometimes seen in the inpatient setting—were not apparent during my colleague’s care. However, aspects considered trivial from a doctor’s point of view, such as pre-procedural fasting, lack of privacy, and room changes became acutely intrusive.

Second, my colleague observed that her treatment team was overly solicitous. They wanted her to be pain-free and organized “urgent” tests to minimize waiting time. She recognized that there was an overt obligation to procure excessive investigations and treatment compared with a usual patient, because there was wariness of her vigilance of when things go wrong or are overlooked.

This situation was a reminder that clinicians should be mindful of finding the middle ground between unnecessary treatment for a “doctor as patient” and uninformed treatment for a “standard patient.”

Seek to understand

Role reversal represents the fundamental skill of connecting with others through self-awareness, self-regulation, and empathy.³ Studies have found that doctors who have assumed the patient role show more empathy and possess better communication skills.⁴ The situation for the doctor who becomes a patient may be disconcerting, but the “do no harm” nature of medicine and the generally accepting demeanor of patients render the relationship between empathy and role reversal especially harmonious. Although it is comfortable and convenient to stay on one side of the relationship, grasping an emotional representation of the other side is essential. It is the process of overcoming egocentricity and perceiving the subjective experience of the other role that is rewarding. We all desire to be understood, but to be understood, we must first seek to understand.

AT THE ANNUAL MEETING ON WOMEN’S CANCER 

NATIONAL HARBOR, MD. – Patients with endometrial cancer and isolated tumor cells in sentinel lymph nodes had excellent short-term outcomes, even if they opted out of adjuvant chemotherapy or radiation therapy.

In a single-center prospective study, all 10 such patients remained alive and free of disease progression at 3 years, Marie Plante, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology.

The finding suggests that isolated tumor cells in sentinel lymph nodes are not, by themselves, an indication for adjuvant therapy in women with endometrial cancer, said Dr. Plante of Laval University in Quebec City. The issue remains controversial, however, and merits larger cohort studies with longer-term follow-up, she acknowledged.

Ultrastaging of sentinel lymph node biopsies that are negative on hematoxylin and eosin staining has boosted the detection of low-volume metastases. In the case of endometrial cancer with isolated tumor cells, there is a dilemma about whether to recommend adjuvant therapy. Very few studies have examined this relatively rare patient subgroup.

This study included 519 patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy, and sentinel lymph node mapping for endometrial cancer. Pathologic ultrastaging identified 31 patients with isolated tumor cells (6%), of whom 11 received adjuvant chemotherapy, 14 received pelvic radiation therapy, and 10 received brachytherapy or observation only.

Only one patient with isolated tumor cells developed recurrent disease within 3 years. This patient had a 7-cm carcinosarcoma that recurred despite adjuvant chemotherapy and radiation therapy. There were no recurrences among patients with endometrioid histology, Dr. Plante noted.

Dr. Plante cited no funding sources and reported having no conflicts of interest.

[email protected]

AT THE ANNUAL MEETING ON WOMEN’S CANCER 

NATIONAL HARBOR, MD. – Patients with endometrial cancer and isolated tumor cells in sentinel lymph nodes had excellent short-term outcomes, even if they opted out of adjuvant chemotherapy or radiation therapy.

In a single-center prospective study, all 10 such patients remained alive and free of disease progression at 3 years, Marie Plante, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology.

The finding suggests that isolated tumor cells in sentinel lymph nodes are not, by themselves, an indication for adjuvant therapy in women with endometrial cancer, said Dr. Plante of Laval University in Quebec City. The issue remains controversial, however, and merits larger cohort studies with longer-term follow-up, she acknowledged.

Ultrastaging of sentinel lymph node biopsies that are negative on hematoxylin and eosin staining has boosted the detection of low-volume metastases. In the case of endometrial cancer with isolated tumor cells, there is a dilemma about whether to recommend adjuvant therapy. Very few studies have examined this relatively rare patient subgroup.

This study included 519 patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy, and sentinel lymph node mapping for endometrial cancer. Pathologic ultrastaging identified 31 patients with isolated tumor cells (6%), of whom 11 received adjuvant chemotherapy, 14 received pelvic radiation therapy, and 10 received brachytherapy or observation only.

Only one patient with isolated tumor cells developed recurrent disease within 3 years. This patient had a 7-cm carcinosarcoma that recurred despite adjuvant chemotherapy and radiation therapy. There were no recurrences among patients with endometrioid histology, Dr. Plante noted.

Dr. Plante cited no funding sources and reported having no conflicts of interest.

[email protected]

AT THE ANNUAL MEETING ON WOMEN’S CANCER 

NATIONAL HARBOR, MD. – Patients with endometrial cancer and isolated tumor cells in sentinel lymph nodes had excellent short-term outcomes, even if they opted out of adjuvant chemotherapy or radiation therapy.

In a single-center prospective study, all 10 such patients remained alive and free of disease progression at 3 years, Marie Plante, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology.

The finding suggests that isolated tumor cells in sentinel lymph nodes are not, by themselves, an indication for adjuvant therapy in women with endometrial cancer, said Dr. Plante of Laval University in Quebec City. The issue remains controversial, however, and merits larger cohort studies with longer-term follow-up, she acknowledged.

Ultrastaging of sentinel lymph node biopsies that are negative on hematoxylin and eosin staining has boosted the detection of low-volume metastases. In the case of endometrial cancer with isolated tumor cells, there is a dilemma about whether to recommend adjuvant therapy. Very few studies have examined this relatively rare patient subgroup.

This study included 519 patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy, and sentinel lymph node mapping for endometrial cancer. Pathologic ultrastaging identified 31 patients with isolated tumor cells (6%), of whom 11 received adjuvant chemotherapy, 14 received pelvic radiation therapy, and 10 received brachytherapy or observation only.

Only one patient with isolated tumor cells developed recurrent disease within 3 years. This patient had a 7-cm carcinosarcoma that recurred despite adjuvant chemotherapy and radiation therapy. There were no recurrences among patients with endometrioid histology, Dr. Plante noted.

Dr. Plante cited no funding sources and reported having no conflicts of interest.

[email protected]

MIAMI BEACH – Often people living with cancer hesitate to ask their providers about sensitive and important issues surrounding sexuality and fertility. At the same time, some clinicians remain uncomfortable raising questions regarding sexual function or simply lack the time to appropriately address the issues during a patient encounter.

A new online resource aims to solve both problems simultaneously, giving both patients and providers the tools to meaningfully address sexuality and fertility issues, Leslie R. Schover, PhD, said in a video interview at the annual Miami Breast Cancer Conference, held by Physicians’ Education Resource.

The Will2love.com site features first-person patient account videos from women and men who faced similar concerns, said Dr. Schover, founder of the Will2Love digital health company based in Houston. In addition, vignettes with actors inform patients and also model how oncologists, oncology nurses, and other staff could effectively communicate with concerned patients. A professional portal offers online skills training for clinicians.

[email protected]

MIAMI BEACH – Often people living with cancer hesitate to ask their providers about sensitive and important issues surrounding sexuality and fertility. At the same time, some clinicians remain uncomfortable raising questions regarding sexual function or simply lack the time to appropriately address the issues during a patient encounter.

A new online resource aims to solve both problems simultaneously, giving both patients and providers the tools to meaningfully address sexuality and fertility issues, Leslie R. Schover, PhD, said in a video interview at the annual Miami Breast Cancer Conference, held by Physicians’ Education Resource.

The Will2love.com site features first-person patient account videos from women and men who faced similar concerns, said Dr. Schover, founder of the Will2Love digital health company based in Houston. In addition, vignettes with actors inform patients and also model how oncologists, oncology nurses, and other staff could effectively communicate with concerned patients. A professional portal offers online skills training for clinicians.

[email protected]

MIAMI BEACH – Often people living with cancer hesitate to ask their providers about sensitive and important issues surrounding sexuality and fertility. At the same time, some clinicians remain uncomfortable raising questions regarding sexual function or simply lack the time to appropriately address the issues during a patient encounter.

A new online resource aims to solve both problems simultaneously, giving both patients and providers the tools to meaningfully address sexuality and fertility issues, Leslie R. Schover, PhD, said in a video interview at the annual Miami Breast Cancer Conference, held by Physicians’ Education Resource.

The Will2love.com site features first-person patient account videos from women and men who faced similar concerns, said Dr. Schover, founder of the Will2Love digital health company based in Houston. In addition, vignettes with actors inform patients and also model how oncologists, oncology nurses, and other staff could effectively communicate with concerned patients. A professional portal offers online skills training for clinicians.

[email protected]

SNOWMASS, COLO. – The continental United States is vulnerable to an epidemic of chikungunya virus disease, an event which would have profound consequences for rheumatologists, Robert T. Schoen, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

“We certainly have all the factors in place where we could have a major epidemic of chikungunya, particularly in Florida, Texas, and neighboring states. As rheumatologists, I think we can own this infection if we want to because it causes an arthritis that is a true arthritis in a significant percentage of patients,” said Dr. Schoen, a rheumatologist at Yale University in New Haven, Conn.

Bruce Jancin/Frontline Medical News

Course of illness

The rate of asymptomatic infection has been variously estimated at 3%-25%. Symptomatic chikungunya is a biphasic illness. After a 2- to 6-day incubation period, patients develop rapid-onset fever with severe joint pain and muscle aches. Indeed, chikungunya means “bent over” in Makonde, an African Bantu language.

Roughly 60% of patients develop a rash during the acute febrile phase of the illness, which lasts about a week. The dermatitis is most often a maculopapular rash on the trunk which is “absolutely indistinguishable” from the rash caused by Zika virus infection, transmitted by the same vectors, Dr. Schoen noted.

During this acute phase, almost all patients develop a severe polyarthritis which can last for weeks or, less commonly, for months or years. This polyarthritis mimics seronegative rheumatoid arthritis. It is usually symmetric and often affects the hands, wrists, and feet.

The acute febrile phase is characterized by high levels of viremia, with up to 1 billion viral particles per milliliter of blood. During this period, definitive diagnosis of chikungunya can be made through reverse transcriptase–polymerase chain reaction testing or viral culture.

Typically, though, patients make their way to a rheumatologist only well after the viremic period is over. In that situation, the diagnostic mainstay is serologic testing. Antichikungunya virus Immunoglobulin M is detectable starting on about day 5 after symptom onset, and it persists for the next 1-3 months. Immunoglobulin G (IgG) antibodies become detectable in the same time frame and remain elevated for years.

Dr. Schoen highlighted a small but intriguing study from Singapore that suggests that the early appearance of chikungunya-specific neutralizing IgG3–antibodies may constitute a marker for favorable long-term prognosis. The observational study involved 30 patients hospitalized for severe acute chikungunya infection. The investigators classified them into two groups: 14 patients had low levels of acute viremia, a less severe acute illness, and late development of IgG3 antibodies; the other 16 had a high initial viral load, a more severe acute phase, and a rapid IgG3 and interleukin-6 response to infection.

The patients with a robust early IgG3 response cleared the virus faster and none of them developed chronic arthritis. In contrast, those without early, chikungunya-specific IgG3 had a high rate of persistent arthralgia (J Infect Dis. 2012 Apr 1;205[7]:1147-54).
 

Treatment

No evidence-based treatment for chikungunya exists. Treatment in the acute phase is primarily supportive care. Rheumatologists on the Caribbean island of Martinique have reported a favorable experience using methotrexate at doses up to 25 mg/week or with standard doses of anti–tumor necrosis factor agents in chikungunya patients with severe bilateral symmetric chronic inflammatory joint disease arising during the 2013-2015 epidemic. The treatment response and tolerability were comparable with the results typically obtained in rheumatoid arthritis patients, according to the rheumatologists (Arthritis Rheumatol. 2016 Nov;68[11]:2817-24).

Dr. Schoen found the report from Martinique to be reassuring. He too has resorted to familiar rheumatologic medications in his severely affected patients. Anecdotally, his greatest success involved a patient with a 5-year history of disabling chikungunya polyarthritis who showed marked improvement after several months on hydroxychloroquine.

The Martinique investigators also reported on 22 patients who developed chikungunya while on biologic agents for rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, or systemic lupus erythematosus. The biologics weren’t protective against the viral disease in these patients. All 22 of them developed severe acute chikungunya polyarthritis with a mean swollen joint count of 9.6 (Joint Bone Spine. 2016 Mar;83[2]:245-6).
 

Infection during pregnancy

There is a legitimate concern about chikungunya infection occurring during pregnancy, but, based on the experiences documented on Reunion Island, the risk to the baby is confined to intrapartum exposure in a viremic mother.

Reunion Island is a French region in the Indian Ocean off the eastern coast of Africa. It has first-world medical care. Much of the best documented early work on chikungunya outbreaks grew out of the 2005-2006 epidemic there, which affected more than one-third of the island’s 800,000-plus residents.

In a prospective study of 7,504 deliveries on the island during a 22-month period, mother-to-child transmission of chikungunya occurred only in the context of intrapartum viremia, with 19 cases of vertical transmission occurring among 39 affected mothers who delivered at a median 38 weeks of gestation. Cesarean section had no protective effect. All 19 infected neonates were asymptomatic at birth, with median onset of pain, fever, and thrombocytopenia on day 4. Nine of the 19 infected neonates developed encephalopathy with pathologic MRI findings, including cerebral hemorrhage in two cases (PLoS Med. 2008 Mar 18;5[3]:e60).

The case fatality rate for chikungunya is low at 0.1%. Most deaths occur in young children or elderly individuals with major comorbid conditions. Despite this low mortality, interest in chikungunya vaccine development is being driven by the infection’s impact on tourism, its spread to temperate climates, the economic impact of the considerable time lost from work, and military need. A promising attenuated, virus-like, particle-based vaccine is currently in phase II testing in the Caribbean.

Dr. Schoen reported having no financial conflicts.

[email protected]
 

SNOWMASS, COLO. – The continental United States is vulnerable to an epidemic of chikungunya virus disease, an event which would have profound consequences for rheumatologists, Robert T. Schoen, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

“We certainly have all the factors in place where we could have a major epidemic of chikungunya, particularly in Florida, Texas, and neighboring states. As rheumatologists, I think we can own this infection if we want to because it causes an arthritis that is a true arthritis in a significant percentage of patients,” said Dr. Schoen, a rheumatologist at Yale University in New Haven, Conn.

Bruce Jancin/Frontline Medical News

Course of illness

The rate of asymptomatic infection has been variously estimated at 3%-25%. Symptomatic chikungunya is a biphasic illness. After a 2- to 6-day incubation period, patients develop rapid-onset fever with severe joint pain and muscle aches. Indeed, chikungunya means “bent over” in Makonde, an African Bantu language.

Roughly 60% of patients develop a rash during the acute febrile phase of the illness, which lasts about a week. The dermatitis is most often a maculopapular rash on the trunk which is “absolutely indistinguishable” from the rash caused by Zika virus infection, transmitted by the same vectors, Dr. Schoen noted.

During this acute phase, almost all patients develop a severe polyarthritis which can last for weeks or, less commonly, for months or years. This polyarthritis mimics seronegative rheumatoid arthritis. It is usually symmetric and often affects the hands, wrists, and feet.

The acute febrile phase is characterized by high levels of viremia, with up to 1 billion viral particles per milliliter of blood. During this period, definitive diagnosis of chikungunya can be made through reverse transcriptase–polymerase chain reaction testing or viral culture.

Typically, though, patients make their way to a rheumatologist only well after the viremic period is over. In that situation, the diagnostic mainstay is serologic testing. Antichikungunya virus Immunoglobulin M is detectable starting on about day 5 after symptom onset, and it persists for the next 1-3 months. Immunoglobulin G (IgG) antibodies become detectable in the same time frame and remain elevated for years.

Dr. Schoen highlighted a small but intriguing study from Singapore that suggests that the early appearance of chikungunya-specific neutralizing IgG3–antibodies may constitute a marker for favorable long-term prognosis. The observational study involved 30 patients hospitalized for severe acute chikungunya infection. The investigators classified them into two groups: 14 patients had low levels of acute viremia, a less severe acute illness, and late development of IgG3 antibodies; the other 16 had a high initial viral load, a more severe acute phase, and a rapid IgG3 and interleukin-6 response to infection.

The patients with a robust early IgG3 response cleared the virus faster and none of them developed chronic arthritis. In contrast, those without early, chikungunya-specific IgG3 had a high rate of persistent arthralgia (J Infect Dis. 2012 Apr 1;205[7]:1147-54).
 

Treatment

No evidence-based treatment for chikungunya exists. Treatment in the acute phase is primarily supportive care. Rheumatologists on the Caribbean island of Martinique have reported a favorable experience using methotrexate at doses up to 25 mg/week or with standard doses of anti–tumor necrosis factor agents in chikungunya patients with severe bilateral symmetric chronic inflammatory joint disease arising during the 2013-2015 epidemic. The treatment response and tolerability were comparable with the results typically obtained in rheumatoid arthritis patients, according to the rheumatologists (Arthritis Rheumatol. 2016 Nov;68[11]:2817-24).

Dr. Schoen found the report from Martinique to be reassuring. He too has resorted to familiar rheumatologic medications in his severely affected patients. Anecdotally, his greatest success involved a patient with a 5-year history of disabling chikungunya polyarthritis who showed marked improvement after several months on hydroxychloroquine.

The Martinique investigators also reported on 22 patients who developed chikungunya while on biologic agents for rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, or systemic lupus erythematosus. The biologics weren’t protective against the viral disease in these patients. All 22 of them developed severe acute chikungunya polyarthritis with a mean swollen joint count of 9.6 (Joint Bone Spine. 2016 Mar;83[2]:245-6).
 

Infection during pregnancy

There is a legitimate concern about chikungunya infection occurring during pregnancy, but, based on the experiences documented on Reunion Island, the risk to the baby is confined to intrapartum exposure in a viremic mother.

Reunion Island is a French region in the Indian Ocean off the eastern coast of Africa. It has first-world medical care. Much of the best documented early work on chikungunya outbreaks grew out of the 2005-2006 epidemic there, which affected more than one-third of the island’s 800,000-plus residents.

In a prospective study of 7,504 deliveries on the island during a 22-month period, mother-to-child transmission of chikungunya occurred only in the context of intrapartum viremia, with 19 cases of vertical transmission occurring among 39 affected mothers who delivered at a median 38 weeks of gestation. Cesarean section had no protective effect. All 19 infected neonates were asymptomatic at birth, with median onset of pain, fever, and thrombocytopenia on day 4. Nine of the 19 infected neonates developed encephalopathy with pathologic MRI findings, including cerebral hemorrhage in two cases (PLoS Med. 2008 Mar 18;5[3]:e60).

The case fatality rate for chikungunya is low at 0.1%. Most deaths occur in young children or elderly individuals with major comorbid conditions. Despite this low mortality, interest in chikungunya vaccine development is being driven by the infection’s impact on tourism, its spread to temperate climates, the economic impact of the considerable time lost from work, and military need. A promising attenuated, virus-like, particle-based vaccine is currently in phase II testing in the Caribbean.

Dr. Schoen reported having no financial conflicts.

[email protected]
 

SNOWMASS, COLO. – The continental United States is vulnerable to an epidemic of chikungunya virus disease, an event which would have profound consequences for rheumatologists, Robert T. Schoen, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

“We certainly have all the factors in place where we could have a major epidemic of chikungunya, particularly in Florida, Texas, and neighboring states. As rheumatologists, I think we can own this infection if we want to because it causes an arthritis that is a true arthritis in a significant percentage of patients,” said Dr. Schoen, a rheumatologist at Yale University in New Haven, Conn.

Bruce Jancin/Frontline Medical News

Course of illness

The rate of asymptomatic infection has been variously estimated at 3%-25%. Symptomatic chikungunya is a biphasic illness. After a 2- to 6-day incubation period, patients develop rapid-onset fever with severe joint pain and muscle aches. Indeed, chikungunya means “bent over” in Makonde, an African Bantu language.

Roughly 60% of patients develop a rash during the acute febrile phase of the illness, which lasts about a week. The dermatitis is most often a maculopapular rash on the trunk which is “absolutely indistinguishable” from the rash caused by Zika virus infection, transmitted by the same vectors, Dr. Schoen noted.

During this acute phase, almost all patients develop a severe polyarthritis which can last for weeks or, less commonly, for months or years. This polyarthritis mimics seronegative rheumatoid arthritis. It is usually symmetric and often affects the hands, wrists, and feet.

The acute febrile phase is characterized by high levels of viremia, with up to 1 billion viral particles per milliliter of blood. During this period, definitive diagnosis of chikungunya can be made through reverse transcriptase–polymerase chain reaction testing or viral culture.

Typically, though, patients make their way to a rheumatologist only well after the viremic period is over. In that situation, the diagnostic mainstay is serologic testing. Antichikungunya virus Immunoglobulin M is detectable starting on about day 5 after symptom onset, and it persists for the next 1-3 months. Immunoglobulin G (IgG) antibodies become detectable in the same time frame and remain elevated for years.

Dr. Schoen highlighted a small but intriguing study from Singapore that suggests that the early appearance of chikungunya-specific neutralizing IgG3–antibodies may constitute a marker for favorable long-term prognosis. The observational study involved 30 patients hospitalized for severe acute chikungunya infection. The investigators classified them into two groups: 14 patients had low levels of acute viremia, a less severe acute illness, and late development of IgG3 antibodies; the other 16 had a high initial viral load, a more severe acute phase, and a rapid IgG3 and interleukin-6 response to infection.

The patients with a robust early IgG3 response cleared the virus faster and none of them developed chronic arthritis. In contrast, those without early, chikungunya-specific IgG3 had a high rate of persistent arthralgia (J Infect Dis. 2012 Apr 1;205[7]:1147-54).
 

Treatment

No evidence-based treatment for chikungunya exists. Treatment in the acute phase is primarily supportive care. Rheumatologists on the Caribbean island of Martinique have reported a favorable experience using methotrexate at doses up to 25 mg/week or with standard doses of anti–tumor necrosis factor agents in chikungunya patients with severe bilateral symmetric chronic inflammatory joint disease arising during the 2013-2015 epidemic. The treatment response and tolerability were comparable with the results typically obtained in rheumatoid arthritis patients, according to the rheumatologists (Arthritis Rheumatol. 2016 Nov;68[11]:2817-24).

Dr. Schoen found the report from Martinique to be reassuring. He too has resorted to familiar rheumatologic medications in his severely affected patients. Anecdotally, his greatest success involved a patient with a 5-year history of disabling chikungunya polyarthritis who showed marked improvement after several months on hydroxychloroquine.

The Martinique investigators also reported on 22 patients who developed chikungunya while on biologic agents for rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, or systemic lupus erythematosus. The biologics weren’t protective against the viral disease in these patients. All 22 of them developed severe acute chikungunya polyarthritis with a mean swollen joint count of 9.6 (Joint Bone Spine. 2016 Mar;83[2]:245-6).
 

Infection during pregnancy

There is a legitimate concern about chikungunya infection occurring during pregnancy, but, based on the experiences documented on Reunion Island, the risk to the baby is confined to intrapartum exposure in a viremic mother.

Reunion Island is a French region in the Indian Ocean off the eastern coast of Africa. It has first-world medical care. Much of the best documented early work on chikungunya outbreaks grew out of the 2005-2006 epidemic there, which affected more than one-third of the island’s 800,000-plus residents.

In a prospective study of 7,504 deliveries on the island during a 22-month period, mother-to-child transmission of chikungunya occurred only in the context of intrapartum viremia, with 19 cases of vertical transmission occurring among 39 affected mothers who delivered at a median 38 weeks of gestation. Cesarean section had no protective effect. All 19 infected neonates were asymptomatic at birth, with median onset of pain, fever, and thrombocytopenia on day 4. Nine of the 19 infected neonates developed encephalopathy with pathologic MRI findings, including cerebral hemorrhage in two cases (PLoS Med. 2008 Mar 18;5[3]:e60).

The case fatality rate for chikungunya is low at 0.1%. Most deaths occur in young children or elderly individuals with major comorbid conditions. Despite this low mortality, interest in chikungunya vaccine development is being driven by the infection’s impact on tourism, its spread to temperate climates, the economic impact of the considerable time lost from work, and military need. A promising attenuated, virus-like, particle-based vaccine is currently in phase II testing in the Caribbean.

Dr. Schoen reported having no financial conflicts.

[email protected]
 

A 55-year-old man who had experienced discolored nasal drainage and mucus plugs in the right side of his nose for 5 years was referred to the ear, nose, and throat clinic. A computerized tomography (CT) scan showed opacification of the right ethmoid and maxillary sinuses and periapical radiolucency in the first and second right maxillary molars (Figure 1).

The patient was treated with antibiotics (amoxicillin and clavulanate; moxifloxacin) and nasal rinses but failed to improve.

The maxillary molars were considered the source of the persistent sinus infection, and the patient was referred to oral surgery for extraction. Three months after oral surgery, the extraction sites were completely healed, and the right maxillary sinus appeared free of disease endoscopically (Figure 3).

A 55-year-old man who had experienced discolored nasal drainage and mucus plugs in the right side of his nose for 5 years was referred to the ear, nose, and throat clinic. A computerized tomography (CT) scan showed opacification of the right ethmoid and maxillary sinuses and periapical radiolucency in the first and second right maxillary molars (Figure 1).

The patient was treated with antibiotics (amoxicillin and clavulanate; moxifloxacin) and nasal rinses but failed to improve.

The maxillary molars were considered the source of the persistent sinus infection, and the patient was referred to oral surgery for extraction. Three months after oral surgery, the extraction sites were completely healed, and the right maxillary sinus appeared free of disease endoscopically (Figure 3).

A 55-year-old man who had experienced discolored nasal drainage and mucus plugs in the right side of his nose for 5 years was referred to the ear, nose, and throat clinic. A computerized tomography (CT) scan showed opacification of the right ethmoid and maxillary sinuses and periapical radiolucency in the first and second right maxillary molars (Figure 1).

The patient was treated with antibiotics (amoxicillin and clavulanate; moxifloxacin) and nasal rinses but failed to improve.

The maxillary molars were considered the source of the persistent sinus infection, and the patient was referred to oral surgery for extraction. Three months after oral surgery, the extraction sites were completely healed, and the right maxillary sinus appeared free of disease endoscopically (Figure 3).

Photo by Chad McNeeley

ORLANDO, FL—Minimal residual disease (MRD) measurements before and after hematopoietic stem cell transplant (HSCT) can help predict outcomes in patients with childhood acute lymphoblastic leukemia (ALL), according to researchers.

Their work also suggests several other factors can be used to predict event-free survival (EFS) in this patient population, and the team developed risk scores incorporating these factors.

Michael A. Pulsipher, MD, of Children’s Hospital Los Angeles in California, presented this work as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 4*).

“The new risk scores that we were able to develop very nicely predict outcomes post-transplant and can guide study planning,” Dr Pulsipher said.

“MRD pre-transplant was a very powerful predictor of outcome, and MRD post-transplant highlights individual patients at risk.”

For this study, Dr Pulsipher and his colleagues retrospectively analyzed 747 patients treated in Europe, North America, and Australia. The patients received transplants between September 1999 and May 2015.

Most patients had pre-B ALL (78%, n=586), 19% (n=145) had T-cell ALL, 2% had “other” ALLs (n=8) or no data on ALL type (n=8). Sixty-two percent (n=466) were male.

Nearly half of patients were between the ages of 2 and 10 (49%, n=365), 47% (n=351) were older than 10, and 4% (n=31) were younger than 2.

Transplant details

Patients received grafts from matched unrelated donors (42%, n=314), matched sibling donors (30%, n=227), mismatched donors (10%, n=75), and cord blood from unrelated donors (17%, n=128). There was no data on donor type for 3 patients.

Most patients received bone marrow transplants (61%, n=458), 20% (n=147) received cord blood, and 18% (n=131) received peripheral blood stem cells. Eight patients received “other” types of transplants, and 3 patients had no data on stem cell source.

More than half of the patients (55%, n=410) were in their second complete remission (CR) at transplant. Thirty-seven percent were in their first CR (n=275), 7% were in their third or greater CR (n=53), and 1% were not in remission (n=7). Two patients had no data on remission status.

MRD

MRD was assessed before HSCT as well as after—on or near days 30, 60, 90, 180, 365, and beyond.

There were 4 MRD categories:

• MRD negative: No signal
• MRD low: >0 to <10^-4 (<0.01%)
• MRD high: ≥10^-4 to <10^-3 (0.01 to 0.1%)
• MRD very high: ≥10^-3 to <10^-2 (>0.1%).

Dr Pulsipher noted that, when analyzing MRD pre-HSCT or at 30 days after HSCT, the estimated 5-year EFS was similar for patients in the MRD-negative and MRD-low groups. However, as time went on (at days 90, 180, and 365), any detectable level of MRD was associated with a poor prognosis.

“And patients arriving at day 365 with no detectable MRD had an exceptional prognosis, with survival approaching 90%,” Dr Pulsipher said.

He also pointed out an interaction between acute graft-vs-host disease (aGVHD) and MRD post-HSCT. He and his colleagues observed better survival for MRD-positive patients with aGVHD (grade 1-2) than for MRD-positive patients without aGVHD.

Pre-HSCT risk score

Via an adjusted Cox regression analysis, the researchers identified several pre-transplant factors that predicted EFS at 18 months.

These included remission status, donor type, immunophenotype, and MRD. The researchers assigned points to each of these factors to create a risk score.

Compared to patients in first CR, the hazard ratio (HR) for patients in early second CR was 2.53, and the score was 3. For patients in third CR or greater, the HR was 1.95, and the score was 2.

Compared to patients with a matched sibling donor, the HR for patients with a mismatched donor was 1.41, and the score was 1. For patients who received cord blood from an unrelated donor, the HR was 1.48, and the score was 1.

Compared to patients with T-cell ALL, the HR for patients with pre-B ALL was 1.35, and the score was 1.

Compared to patients with MRD <10^-4, the HR for patients with MRD ≥10^-4 was 2.32, and the score was 2.

The probability of EFS at 18 months was 78% ± 2% for patients with 0 to 1 points, 54% ± 3% for those with 2 to 3 points, and 46% ± 5% for patients with 4 or more points.

Day 30 post-HSCT risk score

When considering patients at day 30 post-HSCT, factors that predicted 18-month EFS included remission status, donor type, immunophenotype, aGVHD status, and MRD.

The HR for patients in early second CR was 2.51, and the score was 3. For patients in third CR or greater, the HR was 2.09, and the score was 2.

The HR for patients with a mismatched donor was 1.75, and the score was 2. The HR for patients with pre-B ALL was 1.40, and the score was 1.

Compared to patients with grade 1-2 aGVHD, the HR was 2.02 for patients with grade 0 aGVHD, and the score was 2. For patients with grade 3 aGVHD, the HR was 1.44, and the score was 1. For patients with grade 4 aGVHD, the HR was 7.12, and the score was 7.

The researchers evaluated MRD prior to HSCT and MRD at day 30, using a reference of MRD <10^-4 at both time points. For patients with MRD <10^-4 pre-HSCT and ≥10^-4 at day 30, the HR was 2.29, and the score was 2.

For patients with MRD ≥10^-4 pre-HSCT and <10^-4 at day 30, the HR was 3.17, and the score was 3. For patients with MRD ≥10^-4 pre-HSCT and at day 30, the HR was 3.63, and the score was 4.

The probability of EFS at 18 months was 80% ± 2% for patients with 0 to 3 points, 54% ± 4% for those with 4 to 6 points, and 25% ± 6% for those with 7 or more points.

Day 90 post-HSCT risk score

When considering patients at day 90 post-HSCT, factors that predicted 18-month EFS included remission status, aGVHD status, and MRD.

For patients in early second CR, the HR was 2.81, and the score was 3. For those in third CR or greater, the HR was 1.85, and the score was 2.

Compared to patients with grade 1-2 aGVHD, the HR was 1.60 for patients with grade 0 aGVHD, and the score was 2. For patients with grade 4 aGVHD, the HR was 2.49, and the score was 2.

The researchers assessed MRD prior to HSCT and MRD at day 90, using a reference of MRD <10^-4 at both time points. For patients with MRD <10^-4 pre-HSCT and ≥10^-4 at day 90, the HR was 6.03, and the score was 6.

For patients with MRD ≥10^-4 pre-HSCT and <10^-4 at day 90, the HR was 3.11, and the score was 3. For patients with MRD ≥10^-4 pre-HSCT and at day 90, the HR was 4.59, and the score was 5.

The probability of EFS at 18 months was 83% ± 2% for patients with 0 to 2 points, 60% ± 4% for those with 3 to 5 points, and 17% ± 11 for those with 6 or more points.

*Information in the abstract differs from the presentation.

Photo by Chad McNeeley

ORLANDO, FL—Minimal residual disease (MRD) measurements before and after hematopoietic stem cell transplant (HSCT) can help predict outcomes in patients with childhood acute lymphoblastic leukemia (ALL), according to researchers.

Their work also suggests several other factors can be used to predict event-free survival (EFS) in this patient population, and the team developed risk scores incorporating these factors.

Michael A. Pulsipher, MD, of Children’s Hospital Los Angeles in California, presented this work as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 4*).

“The new risk scores that we were able to develop very nicely predict outcomes post-transplant and can guide study planning,” Dr Pulsipher said.

“MRD pre-transplant was a very powerful predictor of outcome, and MRD post-transplant highlights individual patients at risk.”

For this study, Dr Pulsipher and his colleagues retrospectively analyzed 747 patients treated in Europe, North America, and Australia. The patients received transplants between September 1999 and May 2015.

Most patients had pre-B ALL (78%, n=586), 19% (n=145) had T-cell ALL, 2% had “other” ALLs (n=8) or no data on ALL type (n=8). Sixty-two percent (n=466) were male.

Nearly half of patients were between the ages of 2 and 10 (49%, n=365), 47% (n=351) were older than 10, and 4% (n=31) were younger than 2.

Transplant details

Patients received grafts from matched unrelated donors (42%, n=314), matched sibling donors (30%, n=227), mismatched donors (10%, n=75), and cord blood from unrelated donors (17%, n=128). There was no data on donor type for 3 patients.

Most patients received bone marrow transplants (61%, n=458), 20% (n=147) received cord blood, and 18% (n=131) received peripheral blood stem cells. Eight patients received “other” types of transplants, and 3 patients had no data on stem cell source.

More than half of the patients (55%, n=410) were in their second complete remission (CR) at transplant. Thirty-seven percent were in their first CR (n=275), 7% were in their third or greater CR (n=53), and 1% were not in remission (n=7). Two patients had no data on remission status.

MRD

MRD was assessed before HSCT as well as after—on or near days 30, 60, 90, 180, 365, and beyond.

There were 4 MRD categories:

• MRD negative: No signal
• MRD low: >0 to <10^-4 (<0.01%)
• MRD high: ≥10^-4 to <10^-3 (0.01 to 0.1%)
• MRD very high: ≥10^-3 to <10^-2 (>0.1%).

Dr Pulsipher noted that, when analyzing MRD pre-HSCT or at 30 days after HSCT, the estimated 5-year EFS was similar for patients in the MRD-negative and MRD-low groups. However, as time went on (at days 90, 180, and 365), any detectable level of MRD was associated with a poor prognosis.

“And patients arriving at day 365 with no detectable MRD had an exceptional prognosis, with survival approaching 90%,” Dr Pulsipher said.

He also pointed out an interaction between acute graft-vs-host disease (aGVHD) and MRD post-HSCT. He and his colleagues observed better survival for MRD-positive patients with aGVHD (grade 1-2) than for MRD-positive patients without aGVHD.

Pre-HSCT risk score

Via an adjusted Cox regression analysis, the researchers identified several pre-transplant factors that predicted EFS at 18 months.

These included remission status, donor type, immunophenotype, and MRD. The researchers assigned points to each of these factors to create a risk score.

Compared to patients in first CR, the hazard ratio (HR) for patients in early second CR was 2.53, and the score was 3. For patients in third CR or greater, the HR was 1.95, and the score was 2.

Compared to patients with a matched sibling donor, the HR for patients with a mismatched donor was 1.41, and the score was 1. For patients who received cord blood from an unrelated donor, the HR was 1.48, and the score was 1.

Compared to patients with T-cell ALL, the HR for patients with pre-B ALL was 1.35, and the score was 1.

Compared to patients with MRD <10^-4, the HR for patients with MRD ≥10^-4 was 2.32, and the score was 2.

The probability of EFS at 18 months was 78% ± 2% for patients with 0 to 1 points, 54% ± 3% for those with 2 to 3 points, and 46% ± 5% for patients with 4 or more points.

Day 30 post-HSCT risk score

When considering patients at day 30 post-HSCT, factors that predicted 18-month EFS included remission status, donor type, immunophenotype, aGVHD status, and MRD.

The HR for patients in early second CR was 2.51, and the score was 3. For patients in third CR or greater, the HR was 2.09, and the score was 2.

The HR for patients with a mismatched donor was 1.75, and the score was 2. The HR for patients with pre-B ALL was 1.40, and the score was 1.

Compared to patients with grade 1-2 aGVHD, the HR was 2.02 for patients with grade 0 aGVHD, and the score was 2. For patients with grade 3 aGVHD, the HR was 1.44, and the score was 1. For patients with grade 4 aGVHD, the HR was 7.12, and the score was 7.

The researchers evaluated MRD prior to HSCT and MRD at day 30, using a reference of MRD <10^-4 at both time points. For patients with MRD <10^-4 pre-HSCT and ≥10^-4 at day 30, the HR was 2.29, and the score was 2.

For patients with MRD ≥10^-4 pre-HSCT and <10^-4 at day 30, the HR was 3.17, and the score was 3. For patients with MRD ≥10^-4 pre-HSCT and at day 30, the HR was 3.63, and the score was 4.

The probability of EFS at 18 months was 80% ± 2% for patients with 0 to 3 points, 54% ± 4% for those with 4 to 6 points, and 25% ± 6% for those with 7 or more points.

Day 90 post-HSCT risk score

When considering patients at day 90 post-HSCT, factors that predicted 18-month EFS included remission status, aGVHD status, and MRD.

For patients in early second CR, the HR was 2.81, and the score was 3. For those in third CR or greater, the HR was 1.85, and the score was 2.

Compared to patients with grade 1-2 aGVHD, the HR was 1.60 for patients with grade 0 aGVHD, and the score was 2. For patients with grade 4 aGVHD, the HR was 2.49, and the score was 2.

The researchers assessed MRD prior to HSCT and MRD at day 90, using a reference of MRD <10^-4 at both time points. For patients with MRD <10^-4 pre-HSCT and ≥10^-4 at day 90, the HR was 6.03, and the score was 6.

For patients with MRD ≥10^-4 pre-HSCT and <10^-4 at day 90, the HR was 3.11, and the score was 3. For patients with MRD ≥10^-4 pre-HSCT and at day 90, the HR was 4.59, and the score was 5.

The probability of EFS at 18 months was 83% ± 2% for patients with 0 to 2 points, 60% ± 4% for those with 3 to 5 points, and 17% ± 11 for those with 6 or more points.

*Information in the abstract differs from the presentation.

Photo by Chad McNeeley

ORLANDO, FL—Minimal residual disease (MRD) measurements before and after hematopoietic stem cell transplant (HSCT) can help predict outcomes in patients with childhood acute lymphoblastic leukemia (ALL), according to researchers.

Their work also suggests several other factors can be used to predict event-free survival (EFS) in this patient population, and the team developed risk scores incorporating these factors.

Michael A. Pulsipher, MD, of Children’s Hospital Los Angeles in California, presented this work as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 4*).

“The new risk scores that we were able to develop very nicely predict outcomes post-transplant and can guide study planning,” Dr Pulsipher said.

“MRD pre-transplant was a very powerful predictor of outcome, and MRD post-transplant highlights individual patients at risk.”

For this study, Dr Pulsipher and his colleagues retrospectively analyzed 747 patients treated in Europe, North America, and Australia. The patients received transplants between September 1999 and May 2015.

Most patients had pre-B ALL (78%, n=586), 19% (n=145) had T-cell ALL, 2% had “other” ALLs (n=8) or no data on ALL type (n=8). Sixty-two percent (n=466) were male.

Nearly half of patients were between the ages of 2 and 10 (49%, n=365), 47% (n=351) were older than 10, and 4% (n=31) were younger than 2.

Transplant details

Patients received grafts from matched unrelated donors (42%, n=314), matched sibling donors (30%, n=227), mismatched donors (10%, n=75), and cord blood from unrelated donors (17%, n=128). There was no data on donor type for 3 patients.

Most patients received bone marrow transplants (61%, n=458), 20% (n=147) received cord blood, and 18% (n=131) received peripheral blood stem cells. Eight patients received “other” types of transplants, and 3 patients had no data on stem cell source.

More than half of the patients (55%, n=410) were in their second complete remission (CR) at transplant. Thirty-seven percent were in their first CR (n=275), 7% were in their third or greater CR (n=53), and 1% were not in remission (n=7). Two patients had no data on remission status.

MRD

MRD was assessed before HSCT as well as after—on or near days 30, 60, 90, 180, 365, and beyond.

There were 4 MRD categories:

• MRD negative: No signal
• MRD low: >0 to <10^-4 (<0.01%)
• MRD high: ≥10^-4 to <10^-3 (0.01 to 0.1%)
• MRD very high: ≥10^-3 to <10^-2 (>0.1%).

Dr Pulsipher noted that, when analyzing MRD pre-HSCT or at 30 days after HSCT, the estimated 5-year EFS was similar for patients in the MRD-negative and MRD-low groups. However, as time went on (at days 90, 180, and 365), any detectable level of MRD was associated with a poor prognosis.

“And patients arriving at day 365 with no detectable MRD had an exceptional prognosis, with survival approaching 90%,” Dr Pulsipher said.

He also pointed out an interaction between acute graft-vs-host disease (aGVHD) and MRD post-HSCT. He and his colleagues observed better survival for MRD-positive patients with aGVHD (grade 1-2) than for MRD-positive patients without aGVHD.

Pre-HSCT risk score

Via an adjusted Cox regression analysis, the researchers identified several pre-transplant factors that predicted EFS at 18 months.

These included remission status, donor type, immunophenotype, and MRD. The researchers assigned points to each of these factors to create a risk score.

Compared to patients in first CR, the hazard ratio (HR) for patients in early second CR was 2.53, and the score was 3. For patients in third CR or greater, the HR was 1.95, and the score was 2.

Compared to patients with a matched sibling donor, the HR for patients with a mismatched donor was 1.41, and the score was 1. For patients who received cord blood from an unrelated donor, the HR was 1.48, and the score was 1.

Compared to patients with T-cell ALL, the HR for patients with pre-B ALL was 1.35, and the score was 1.

Compared to patients with MRD <10^-4, the HR for patients with MRD ≥10^-4 was 2.32, and the score was 2.

The probability of EFS at 18 months was 78% ± 2% for patients with 0 to 1 points, 54% ± 3% for those with 2 to 3 points, and 46% ± 5% for patients with 4 or more points.

Day 30 post-HSCT risk score

When considering patients at day 30 post-HSCT, factors that predicted 18-month EFS included remission status, donor type, immunophenotype, aGVHD status, and MRD.

The HR for patients in early second CR was 2.51, and the score was 3. For patients in third CR or greater, the HR was 2.09, and the score was 2.

The HR for patients with a mismatched donor was 1.75, and the score was 2. The HR for patients with pre-B ALL was 1.40, and the score was 1.

Compared to patients with grade 1-2 aGVHD, the HR was 2.02 for patients with grade 0 aGVHD, and the score was 2. For patients with grade 3 aGVHD, the HR was 1.44, and the score was 1. For patients with grade 4 aGVHD, the HR was 7.12, and the score was 7.

The researchers evaluated MRD prior to HSCT and MRD at day 30, using a reference of MRD <10^-4 at both time points. For patients with MRD <10^-4 pre-HSCT and ≥10^-4 at day 30, the HR was 2.29, and the score was 2.

For patients with MRD ≥10^-4 pre-HSCT and <10^-4 at day 30, the HR was 3.17, and the score was 3. For patients with MRD ≥10^-4 pre-HSCT and at day 30, the HR was 3.63, and the score was 4.

The probability of EFS at 18 months was 80% ± 2% for patients with 0 to 3 points, 54% ± 4% for those with 4 to 6 points, and 25% ± 6% for those with 7 or more points.

Day 90 post-HSCT risk score

When considering patients at day 90 post-HSCT, factors that predicted 18-month EFS included remission status, aGVHD status, and MRD.

For patients in early second CR, the HR was 2.81, and the score was 3. For those in third CR or greater, the HR was 1.85, and the score was 2.

Compared to patients with grade 1-2 aGVHD, the HR was 1.60 for patients with grade 0 aGVHD, and the score was 2. For patients with grade 4 aGVHD, the HR was 2.49, and the score was 2.

The researchers assessed MRD prior to HSCT and MRD at day 90, using a reference of MRD <10^-4 at both time points. For patients with MRD <10^-4 pre-HSCT and ≥10^-4 at day 90, the HR was 6.03, and the score was 6.

For patients with MRD ≥10^-4 pre-HSCT and <10^-4 at day 90, the HR was 3.11, and the score was 3. For patients with MRD ≥10^-4 pre-HSCT and at day 90, the HR was 4.59, and the score was 5.

The probability of EFS at 18 months was 83% ± 2% for patients with 0 to 2 points, 60% ± 4% for those with 3 to 5 points, and 17% ± 11 for those with 6 or more points.

*Information in the abstract differs from the presentation.