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COVID-19: ASTCT provides interim guidelines for transplantation
The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.
The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.
The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
Diagnostic considerations
In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.
These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.
In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.
Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.
With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”
Treatment considerations
“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.
However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).
In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.
Evaluation prior to HCT or cellular therapy
“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.
If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.
In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”
Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.
In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”
Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”
In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”
In the updated ESBMT guidelines, this recommendation was made in reference to the greater spread of COVID-19: “It is therefore strongly recommended to have secured stem cell product access by freezing the product before start of conditioning and, in situations when this is not possible, to have an alternative donor as a backup. For low-risk patients, it is recommended to postpone the start of the transplant procedure if deemed to be safe to do so. This includes both allogeneic and autologous transplant procedures.”
In a recent webinar, Pavan Reddy, MD, of the University of Michigan, Ann Arbor, and ASTCT President; Alpana Waghmare, MD, of the Fred Hutchinson Cancer Research Center, Seattle; and Roy Chemaly, MD, of the MD Anderson Cancer Center, Houston, and chair of the ASTCT Transplant Infectious Disease Special Interest Group, discussed the guidelines and provided some updated information.
Dr. Reddy stated that, at the University of Michigan, they were delaying all nonurgent transplants, largely for myeloma, and are postponing even allotransplants. “The transplants we are not delaying are the high-risk AMLs … and in cases where we truly cannot delay transplants because of patient condition or, in some cases, the donor situation.”
Dr. Chemaly and Dr. Waghmare both agreed that their centers were following a similar approach.
With regard to patient testing, all three institution have recently moved to testing everyone a few days before transplant regardless of symptoms.
They also pointed out that essentially all clinical trials were being put on hold during the crisis, except for those few where patients would be put in danger if the trial were interrupted.
The guidelines discuss in depth the rationale, toxicity, and dosages for use of select agents, including remdesivir, chloroquine/hydroxychloroquine, ribavirin, and tocilizumab. There was some concern expressed about shortages developing in these drugs, which serve a number of other patient communities, in particular the possibility of a tocilizumab shortage was of concern.
Steroids and intravenous immunoglobulins are not are not recommended, according to the guidelines, which also stated that adjunctive therapies such as antibiotics should be considered.
Dr. Chemaly, Dr. Reddy, and Dr. Waghmare did not provide disclosure in the webinar.
The ASTCT recommends following the World Health Organization and CDC COVID-19 pages for continued updates and information on other aspects of the pandemic.
This article was updated 3/26/20.
SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.
There is emerging data regarding coinfection of SARS-CoV-2 with other viruses including infleunza. Immunocompromised hosts, especially transplantation and cellular therapy (TCT) recipients, are known to frequently have more than one pathogen present, especially in pulmonary infections. As the community spread increases, it would be reasonable to obtain concomitant testing for respiratory viruses along with SARS-CoV-2 as recommended. In addition, viral infection can cause secondary bacterial and fungal infections (especially Aspergillus). In the presence of SARS-CoV-2, where it is recommended to avoid bronchoalveolar lavage, we have to keep a high clinical suspicion based on patients’ risk factors.
Based on the latest studies, remdesivir is looking like a promising therapeutic option to treat SARS-CoV-2 infection and is currently available in the United States under a clinical trial and by obtaining an emergency investigational new drug usage. Favipiravir, another antiviral, showed early viral clearance and radiographic improvement in mild cases of COVID-19, but is currently unavailable in the United States. Whereas lopinavir/ritonavir should no longer be first line agents based on the latest data published in The New England Journal of Medicine that showed its lack of efficacy.
Acute Respiratory Distress Syndrome (ARDS) caused by an intense inflammatory response is the main cause of death in COVID-19. Early reports on the use of tocilizumab (an IL-6 receptor blocker) for ARDS to block cytokine mediated injury to the lung should be a consideration early in the course of COVID-19 pneumonitis, especially in setting of high risk for ARDS mortality.
We are considering other IL-6–blocking agents like siltuximab in case of a shortage of tocilizumab while centers scramble to get these agents. It is important to note that any such usages for COVID-19 would be considered off-label.
TCT candidates should of course be practicing social distancing in days leading to transplant to reduce their risk of exposure regardless of state or federal recommendations. Household members of TCT candidates should practice similar caution because transmission has been reported by asymptomatic individuals.
Zainab Shahid, MD, is the medical director of Bone Marrow Transplant Infectious Diseases at the Levine Cancer Institute/Atrium Health and a clinical associate professor of medicine at University of North Carolina at Chapel Hill. She reported that she had no relevant disclosures.
There is emerging data regarding coinfection of SARS-CoV-2 with other viruses including infleunza. Immunocompromised hosts, especially transplantation and cellular therapy (TCT) recipients, are known to frequently have more than one pathogen present, especially in pulmonary infections. As the community spread increases, it would be reasonable to obtain concomitant testing for respiratory viruses along with SARS-CoV-2 as recommended. In addition, viral infection can cause secondary bacterial and fungal infections (especially Aspergillus). In the presence of SARS-CoV-2, where it is recommended to avoid bronchoalveolar lavage, we have to keep a high clinical suspicion based on patients’ risk factors.
Based on the latest studies, remdesivir is looking like a promising therapeutic option to treat SARS-CoV-2 infection and is currently available in the United States under a clinical trial and by obtaining an emergency investigational new drug usage. Favipiravir, another antiviral, showed early viral clearance and radiographic improvement in mild cases of COVID-19, but is currently unavailable in the United States. Whereas lopinavir/ritonavir should no longer be first line agents based on the latest data published in The New England Journal of Medicine that showed its lack of efficacy.
Acute Respiratory Distress Syndrome (ARDS) caused by an intense inflammatory response is the main cause of death in COVID-19. Early reports on the use of tocilizumab (an IL-6 receptor blocker) for ARDS to block cytokine mediated injury to the lung should be a consideration early in the course of COVID-19 pneumonitis, especially in setting of high risk for ARDS mortality.
We are considering other IL-6–blocking agents like siltuximab in case of a shortage of tocilizumab while centers scramble to get these agents. It is important to note that any such usages for COVID-19 would be considered off-label.
TCT candidates should of course be practicing social distancing in days leading to transplant to reduce their risk of exposure regardless of state or federal recommendations. Household members of TCT candidates should practice similar caution because transmission has been reported by asymptomatic individuals.
Zainab Shahid, MD, is the medical director of Bone Marrow Transplant Infectious Diseases at the Levine Cancer Institute/Atrium Health and a clinical associate professor of medicine at University of North Carolina at Chapel Hill. She reported that she had no relevant disclosures.
There is emerging data regarding coinfection of SARS-CoV-2 with other viruses including infleunza. Immunocompromised hosts, especially transplantation and cellular therapy (TCT) recipients, are known to frequently have more than one pathogen present, especially in pulmonary infections. As the community spread increases, it would be reasonable to obtain concomitant testing for respiratory viruses along with SARS-CoV-2 as recommended. In addition, viral infection can cause secondary bacterial and fungal infections (especially Aspergillus). In the presence of SARS-CoV-2, where it is recommended to avoid bronchoalveolar lavage, we have to keep a high clinical suspicion based on patients’ risk factors.
Based on the latest studies, remdesivir is looking like a promising therapeutic option to treat SARS-CoV-2 infection and is currently available in the United States under a clinical trial and by obtaining an emergency investigational new drug usage. Favipiravir, another antiviral, showed early viral clearance and radiographic improvement in mild cases of COVID-19, but is currently unavailable in the United States. Whereas lopinavir/ritonavir should no longer be first line agents based on the latest data published in The New England Journal of Medicine that showed its lack of efficacy.
Acute Respiratory Distress Syndrome (ARDS) caused by an intense inflammatory response is the main cause of death in COVID-19. Early reports on the use of tocilizumab (an IL-6 receptor blocker) for ARDS to block cytokine mediated injury to the lung should be a consideration early in the course of COVID-19 pneumonitis, especially in setting of high risk for ARDS mortality.
We are considering other IL-6–blocking agents like siltuximab in case of a shortage of tocilizumab while centers scramble to get these agents. It is important to note that any such usages for COVID-19 would be considered off-label.
TCT candidates should of course be practicing social distancing in days leading to transplant to reduce their risk of exposure regardless of state or federal recommendations. Household members of TCT candidates should practice similar caution because transmission has been reported by asymptomatic individuals.
Zainab Shahid, MD, is the medical director of Bone Marrow Transplant Infectious Diseases at the Levine Cancer Institute/Atrium Health and a clinical associate professor of medicine at University of North Carolina at Chapel Hill. She reported that she had no relevant disclosures.
The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.
The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.
The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
Diagnostic considerations
In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.
These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.
In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.
Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.
With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”
Treatment considerations
“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.
However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).
In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.
Evaluation prior to HCT or cellular therapy
“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.
If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.
In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”
Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.
In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”
Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”
In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”
In the updated ESBMT guidelines, this recommendation was made in reference to the greater spread of COVID-19: “It is therefore strongly recommended to have secured stem cell product access by freezing the product before start of conditioning and, in situations when this is not possible, to have an alternative donor as a backup. For low-risk patients, it is recommended to postpone the start of the transplant procedure if deemed to be safe to do so. This includes both allogeneic and autologous transplant procedures.”
In a recent webinar, Pavan Reddy, MD, of the University of Michigan, Ann Arbor, and ASTCT President; Alpana Waghmare, MD, of the Fred Hutchinson Cancer Research Center, Seattle; and Roy Chemaly, MD, of the MD Anderson Cancer Center, Houston, and chair of the ASTCT Transplant Infectious Disease Special Interest Group, discussed the guidelines and provided some updated information.
Dr. Reddy stated that, at the University of Michigan, they were delaying all nonurgent transplants, largely for myeloma, and are postponing even allotransplants. “The transplants we are not delaying are the high-risk AMLs … and in cases where we truly cannot delay transplants because of patient condition or, in some cases, the donor situation.”
Dr. Chemaly and Dr. Waghmare both agreed that their centers were following a similar approach.
With regard to patient testing, all three institution have recently moved to testing everyone a few days before transplant regardless of symptoms.
They also pointed out that essentially all clinical trials were being put on hold during the crisis, except for those few where patients would be put in danger if the trial were interrupted.
The guidelines discuss in depth the rationale, toxicity, and dosages for use of select agents, including remdesivir, chloroquine/hydroxychloroquine, ribavirin, and tocilizumab. There was some concern expressed about shortages developing in these drugs, which serve a number of other patient communities, in particular the possibility of a tocilizumab shortage was of concern.
Steroids and intravenous immunoglobulins are not are not recommended, according to the guidelines, which also stated that adjunctive therapies such as antibiotics should be considered.
Dr. Chemaly, Dr. Reddy, and Dr. Waghmare did not provide disclosure in the webinar.
The ASTCT recommends following the World Health Organization and CDC COVID-19 pages for continued updates and information on other aspects of the pandemic.
This article was updated 3/26/20.
SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.
The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.
The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.
The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
Diagnostic considerations
In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.
These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.
In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.
Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.
With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”
Treatment considerations
“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.
However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).
In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.
Evaluation prior to HCT or cellular therapy
“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.
If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.
In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”
Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.
In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”
Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”
In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”
In the updated ESBMT guidelines, this recommendation was made in reference to the greater spread of COVID-19: “It is therefore strongly recommended to have secured stem cell product access by freezing the product before start of conditioning and, in situations when this is not possible, to have an alternative donor as a backup. For low-risk patients, it is recommended to postpone the start of the transplant procedure if deemed to be safe to do so. This includes both allogeneic and autologous transplant procedures.”
In a recent webinar, Pavan Reddy, MD, of the University of Michigan, Ann Arbor, and ASTCT President; Alpana Waghmare, MD, of the Fred Hutchinson Cancer Research Center, Seattle; and Roy Chemaly, MD, of the MD Anderson Cancer Center, Houston, and chair of the ASTCT Transplant Infectious Disease Special Interest Group, discussed the guidelines and provided some updated information.
Dr. Reddy stated that, at the University of Michigan, they were delaying all nonurgent transplants, largely for myeloma, and are postponing even allotransplants. “The transplants we are not delaying are the high-risk AMLs … and in cases where we truly cannot delay transplants because of patient condition or, in some cases, the donor situation.”
Dr. Chemaly and Dr. Waghmare both agreed that their centers were following a similar approach.
With regard to patient testing, all three institution have recently moved to testing everyone a few days before transplant regardless of symptoms.
They also pointed out that essentially all clinical trials were being put on hold during the crisis, except for those few where patients would be put in danger if the trial were interrupted.
The guidelines discuss in depth the rationale, toxicity, and dosages for use of select agents, including remdesivir, chloroquine/hydroxychloroquine, ribavirin, and tocilizumab. There was some concern expressed about shortages developing in these drugs, which serve a number of other patient communities, in particular the possibility of a tocilizumab shortage was of concern.
Steroids and intravenous immunoglobulins are not are not recommended, according to the guidelines, which also stated that adjunctive therapies such as antibiotics should be considered.
Dr. Chemaly, Dr. Reddy, and Dr. Waghmare did not provide disclosure in the webinar.
The ASTCT recommends following the World Health Organization and CDC COVID-19 pages for continued updates and information on other aspects of the pandemic.
This article was updated 3/26/20.
SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.
COVID-19: Older patients with cancer especially vulnerable
For oncologists and other clinicians caring for patients with cancer, the COVID-19 pandemic represents a dynamic clinical challenge that is changing daily and that can feel overwhelming at times, say experts.
“Oncology clinicians are well versed in caring for immunosuppressed patients with cancer, of all ages,” Merry-Jennifer Markham, MD, interim chief of the Division of Hematology and Oncology at the University of Florida Health, Gainesville, told Medscape Medical News.
However, she emphasized that, during this COVID-19 outbreak, “we must be especially diligent about screening for symptoms and exposure, and we must recognize that our older patients with cancer may be especially vulnerable.”
Patients with cancer who are in active treatment are immunosuppressed and are more susceptible to infection and to complications from infection, Markham pointed out. “While we don’t yet have much data on how COVID-19 impacts patients with cancer, I have to suspect that patients undergoing active cancer treatment may be especially vulnerable to the more severe illness associated with COVID-19,” she said.
Indeed, a recent report from China that was published in the Lancet Oncology supports this. The authors suggest that patients with cancer are at higher risk for COVID-19 and have a worse prognosis if they become infected than do those without cancer.
Commonsense rules
Commonsense rules apply for all patients with cancer, regardless of age, said Markham. Measures include thorough handwashing, staying home when sick, and avoiding sick contacts.
Markham, who acts as an expert spokesperson for the American Society of Clinical Oncology, provides information on what patients with cancer need to know about COVID-19 at Cancer.net, the society’s website for patients with cancer.
“Unfortunately, this outbreak of COVID-19 is happening rapidly and in real time,” Markham noted. “The entire medical community is learning as we go, rather than having the luxury of years of evidence-based literature to guide us.”
Another expert agrees. “Unfortunately, there are not a lot of data on how COVID-19 affects cancer patients,” Cardinale Smith, MD, PhD, director of Quality for Cancer Services in the Mount Sinai Health System, New York City, said in an interview.
“We need to minimize the risk for patients and minimize our own exposure by treating this situation like we would a really bad flu season,” Smith told Medscape Medical News. “Some patients have had a bad outcome, but the vast majority do not. The best we can do is stay calm and focused.”
At Mount Sinai, for patients with cancer, routine, nonurgent appointments are being rescheduled for May, Smith said. Those in active treatment are screened by telephone 24 to 48 hours before arrival, after which they undergo a full risk assessment in an isolation room. Those with a respiratory infection are given a mask.
“Patients are very anxious and worried about COVID-19,” said Smith, who has young children and an elderly parent at home. “We don’t have all the answers, and this can heighten anxiety.”
To help allay fears, social workers are asking patients with cancer who express anxiety to discuss their concerns and provide information. A one-page handout on both flu and COVID-10 is available in the waiting room.
The Web portal MyChart gives patients access to updated information on COVID-19 precautions and provides links to the hospital website and to the US Centers for Disease Control and Prevention. Patients who are not feeling well can speak to someone or get answers if they have additional questions.
When counseling patients, Smith advises them to use “an abundance of caution” and to be creative in efforts to minimize risk. “My suggestion is to use FaceTime and Skype to connect and communicate with your community,” she said.
Some churches are conducting services via teleconferencing to minimize risk, and seniors’ centers that offer yoga and other classes are also beginning to provide services virtually, she pointed out.
Data from China
A report published February 14 in the Lancet Oncology appears to be the first analysis in the literature to focus on COVID-19 in patients with cancer.
“Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery,” write the authors, led by Wenhua Liang, MD, of Guangzhou Medical University. However, in correspondence published in the Lancet Oncology, other experts in China question some of Liang’s and colleagues’ findings.
The report by Liang and colleagues concerns a prospective cohort of 1590 patients with COVID-19.
There were 2007 laboratory-confirmed cases of COVID-19 among patients admitted to 575 hospitals throughout China as of January 31. Of those cases, 417 were excluded from the analysis because of insufficient information regarding disease history.
The team reports that of 18 patients with cancer and COVID-19, 39% were at significantly higher risk for “severe events.” By comparison, of 1572 patients with COVID-19 who did not have cancer, 8% were at significantly higher risk (P = .0003). These events included rapid clinical deterioration that required admission to intensive care; invasive ventilation; or death.
Patients with cancer experienced a much more rapid deterioration in clinical status than did those without cancer. The median time to severe events was 13 days, vs 43 days (hazard ratio [HR] adjusted for age, 3.56; P < .0001).
The analysis also shows that patients who underwent chemotherapy or surgery in the past month had a 75% risk of experiencing clinically severe events, compared with a 43% risk for those who had not received recent treatment.
After adjusting for other risk factors, including age and smoking history, older age was the only risk factor for severe events (odds ratio [OR], 1.43; 95% confidence interval [CI], 0.97 – 2.12; P = .072), the study authors say.
Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (20% vs 62%, respectively; P = .294).
Liang and colleagues conclude that these findings provide “a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration.”
The team also proposes three strategies for managing patients with cancer who are at risk for COVID-19 or any other severe infectious disease. They recommend that intentional postponement of adjuvant chemotherapy or elective surgery be considered for patients with stable cancer who live in areas where disease is endemic. Stronger “personal protection provisions” could also be made for patients with cancer or for cancer survivors. Lastly, for patients with cancer who have COVID-19, especially those who are older or who have comorbidities, more intensive surveillance or treatment should be considered.
However, in comments in the Lancet Oncology, other authors in China say these findings should be interpreted with caution.
One group suggests that the increased susceptibility to COVID-19 in patients with cancer could be the result of higher rates of smoking compared with patients who did not have cancer. “Overall, current evidence remains insufficient to explain a conclusive association between cancer and COVID-19,” say Huahao Shen, PhD, of Zhejiang University School of Medicine, Hangzhou, Zhejiang, and colleagues.
Another group suggests that the significantly higher median age of patients with cancer compared with noncancer patients (63 years vs 49 years) may have contributed to poor prognosis.
These authors, led by Li Zhang, MD, PhD, and Hanping Wang, MD, of Peking Union Medical College and the Chinese Academy of Medical Sciences, Beijing, emphasize that patients with cancer need online medical counseling and that critical cases need to be identified and treated.
“In endemic areas outside Wuhan, decisions on whether or not to postpone cancer treatment need to made on a patient-by-patient basis and according to the risk to the patient and the prevailing situation because delays could lead to tumor progression and ultimately poorer outcomes,” they write.
The study was funded by the China National Science Foundation and the Key Project of Guangzhou Scientific Research Project. Liang and coauthors, Shen and coauthors, Zhang, Wang, and Smith have disclosed no relevant financial relationships. Markham has relationships with Aduro Biotech, Lilly, Tesaro, Novartis, and VBL Therapeutics.
This article first appeared on Medscape.com.
For oncologists and other clinicians caring for patients with cancer, the COVID-19 pandemic represents a dynamic clinical challenge that is changing daily and that can feel overwhelming at times, say experts.
“Oncology clinicians are well versed in caring for immunosuppressed patients with cancer, of all ages,” Merry-Jennifer Markham, MD, interim chief of the Division of Hematology and Oncology at the University of Florida Health, Gainesville, told Medscape Medical News.
However, she emphasized that, during this COVID-19 outbreak, “we must be especially diligent about screening for symptoms and exposure, and we must recognize that our older patients with cancer may be especially vulnerable.”
Patients with cancer who are in active treatment are immunosuppressed and are more susceptible to infection and to complications from infection, Markham pointed out. “While we don’t yet have much data on how COVID-19 impacts patients with cancer, I have to suspect that patients undergoing active cancer treatment may be especially vulnerable to the more severe illness associated with COVID-19,” she said.
Indeed, a recent report from China that was published in the Lancet Oncology supports this. The authors suggest that patients with cancer are at higher risk for COVID-19 and have a worse prognosis if they become infected than do those without cancer.
Commonsense rules
Commonsense rules apply for all patients with cancer, regardless of age, said Markham. Measures include thorough handwashing, staying home when sick, and avoiding sick contacts.
Markham, who acts as an expert spokesperson for the American Society of Clinical Oncology, provides information on what patients with cancer need to know about COVID-19 at Cancer.net, the society’s website for patients with cancer.
“Unfortunately, this outbreak of COVID-19 is happening rapidly and in real time,” Markham noted. “The entire medical community is learning as we go, rather than having the luxury of years of evidence-based literature to guide us.”
Another expert agrees. “Unfortunately, there are not a lot of data on how COVID-19 affects cancer patients,” Cardinale Smith, MD, PhD, director of Quality for Cancer Services in the Mount Sinai Health System, New York City, said in an interview.
“We need to minimize the risk for patients and minimize our own exposure by treating this situation like we would a really bad flu season,” Smith told Medscape Medical News. “Some patients have had a bad outcome, but the vast majority do not. The best we can do is stay calm and focused.”
At Mount Sinai, for patients with cancer, routine, nonurgent appointments are being rescheduled for May, Smith said. Those in active treatment are screened by telephone 24 to 48 hours before arrival, after which they undergo a full risk assessment in an isolation room. Those with a respiratory infection are given a mask.
“Patients are very anxious and worried about COVID-19,” said Smith, who has young children and an elderly parent at home. “We don’t have all the answers, and this can heighten anxiety.”
To help allay fears, social workers are asking patients with cancer who express anxiety to discuss their concerns and provide information. A one-page handout on both flu and COVID-10 is available in the waiting room.
The Web portal MyChart gives patients access to updated information on COVID-19 precautions and provides links to the hospital website and to the US Centers for Disease Control and Prevention. Patients who are not feeling well can speak to someone or get answers if they have additional questions.
When counseling patients, Smith advises them to use “an abundance of caution” and to be creative in efforts to minimize risk. “My suggestion is to use FaceTime and Skype to connect and communicate with your community,” she said.
Some churches are conducting services via teleconferencing to minimize risk, and seniors’ centers that offer yoga and other classes are also beginning to provide services virtually, she pointed out.
Data from China
A report published February 14 in the Lancet Oncology appears to be the first analysis in the literature to focus on COVID-19 in patients with cancer.
“Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery,” write the authors, led by Wenhua Liang, MD, of Guangzhou Medical University. However, in correspondence published in the Lancet Oncology, other experts in China question some of Liang’s and colleagues’ findings.
The report by Liang and colleagues concerns a prospective cohort of 1590 patients with COVID-19.
There were 2007 laboratory-confirmed cases of COVID-19 among patients admitted to 575 hospitals throughout China as of January 31. Of those cases, 417 were excluded from the analysis because of insufficient information regarding disease history.
The team reports that of 18 patients with cancer and COVID-19, 39% were at significantly higher risk for “severe events.” By comparison, of 1572 patients with COVID-19 who did not have cancer, 8% were at significantly higher risk (P = .0003). These events included rapid clinical deterioration that required admission to intensive care; invasive ventilation; or death.
Patients with cancer experienced a much more rapid deterioration in clinical status than did those without cancer. The median time to severe events was 13 days, vs 43 days (hazard ratio [HR] adjusted for age, 3.56; P < .0001).
The analysis also shows that patients who underwent chemotherapy or surgery in the past month had a 75% risk of experiencing clinically severe events, compared with a 43% risk for those who had not received recent treatment.
After adjusting for other risk factors, including age and smoking history, older age was the only risk factor for severe events (odds ratio [OR], 1.43; 95% confidence interval [CI], 0.97 – 2.12; P = .072), the study authors say.
Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (20% vs 62%, respectively; P = .294).
Liang and colleagues conclude that these findings provide “a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration.”
The team also proposes three strategies for managing patients with cancer who are at risk for COVID-19 or any other severe infectious disease. They recommend that intentional postponement of adjuvant chemotherapy or elective surgery be considered for patients with stable cancer who live in areas where disease is endemic. Stronger “personal protection provisions” could also be made for patients with cancer or for cancer survivors. Lastly, for patients with cancer who have COVID-19, especially those who are older or who have comorbidities, more intensive surveillance or treatment should be considered.
However, in comments in the Lancet Oncology, other authors in China say these findings should be interpreted with caution.
One group suggests that the increased susceptibility to COVID-19 in patients with cancer could be the result of higher rates of smoking compared with patients who did not have cancer. “Overall, current evidence remains insufficient to explain a conclusive association between cancer and COVID-19,” say Huahao Shen, PhD, of Zhejiang University School of Medicine, Hangzhou, Zhejiang, and colleagues.
Another group suggests that the significantly higher median age of patients with cancer compared with noncancer patients (63 years vs 49 years) may have contributed to poor prognosis.
These authors, led by Li Zhang, MD, PhD, and Hanping Wang, MD, of Peking Union Medical College and the Chinese Academy of Medical Sciences, Beijing, emphasize that patients with cancer need online medical counseling and that critical cases need to be identified and treated.
“In endemic areas outside Wuhan, decisions on whether or not to postpone cancer treatment need to made on a patient-by-patient basis and according to the risk to the patient and the prevailing situation because delays could lead to tumor progression and ultimately poorer outcomes,” they write.
The study was funded by the China National Science Foundation and the Key Project of Guangzhou Scientific Research Project. Liang and coauthors, Shen and coauthors, Zhang, Wang, and Smith have disclosed no relevant financial relationships. Markham has relationships with Aduro Biotech, Lilly, Tesaro, Novartis, and VBL Therapeutics.
This article first appeared on Medscape.com.
For oncologists and other clinicians caring for patients with cancer, the COVID-19 pandemic represents a dynamic clinical challenge that is changing daily and that can feel overwhelming at times, say experts.
“Oncology clinicians are well versed in caring for immunosuppressed patients with cancer, of all ages,” Merry-Jennifer Markham, MD, interim chief of the Division of Hematology and Oncology at the University of Florida Health, Gainesville, told Medscape Medical News.
However, she emphasized that, during this COVID-19 outbreak, “we must be especially diligent about screening for symptoms and exposure, and we must recognize that our older patients with cancer may be especially vulnerable.”
Patients with cancer who are in active treatment are immunosuppressed and are more susceptible to infection and to complications from infection, Markham pointed out. “While we don’t yet have much data on how COVID-19 impacts patients with cancer, I have to suspect that patients undergoing active cancer treatment may be especially vulnerable to the more severe illness associated with COVID-19,” she said.
Indeed, a recent report from China that was published in the Lancet Oncology supports this. The authors suggest that patients with cancer are at higher risk for COVID-19 and have a worse prognosis if they become infected than do those without cancer.
Commonsense rules
Commonsense rules apply for all patients with cancer, regardless of age, said Markham. Measures include thorough handwashing, staying home when sick, and avoiding sick contacts.
Markham, who acts as an expert spokesperson for the American Society of Clinical Oncology, provides information on what patients with cancer need to know about COVID-19 at Cancer.net, the society’s website for patients with cancer.
“Unfortunately, this outbreak of COVID-19 is happening rapidly and in real time,” Markham noted. “The entire medical community is learning as we go, rather than having the luxury of years of evidence-based literature to guide us.”
Another expert agrees. “Unfortunately, there are not a lot of data on how COVID-19 affects cancer patients,” Cardinale Smith, MD, PhD, director of Quality for Cancer Services in the Mount Sinai Health System, New York City, said in an interview.
“We need to minimize the risk for patients and minimize our own exposure by treating this situation like we would a really bad flu season,” Smith told Medscape Medical News. “Some patients have had a bad outcome, but the vast majority do not. The best we can do is stay calm and focused.”
At Mount Sinai, for patients with cancer, routine, nonurgent appointments are being rescheduled for May, Smith said. Those in active treatment are screened by telephone 24 to 48 hours before arrival, after which they undergo a full risk assessment in an isolation room. Those with a respiratory infection are given a mask.
“Patients are very anxious and worried about COVID-19,” said Smith, who has young children and an elderly parent at home. “We don’t have all the answers, and this can heighten anxiety.”
To help allay fears, social workers are asking patients with cancer who express anxiety to discuss their concerns and provide information. A one-page handout on both flu and COVID-10 is available in the waiting room.
The Web portal MyChart gives patients access to updated information on COVID-19 precautions and provides links to the hospital website and to the US Centers for Disease Control and Prevention. Patients who are not feeling well can speak to someone or get answers if they have additional questions.
When counseling patients, Smith advises them to use “an abundance of caution” and to be creative in efforts to minimize risk. “My suggestion is to use FaceTime and Skype to connect and communicate with your community,” she said.
Some churches are conducting services via teleconferencing to minimize risk, and seniors’ centers that offer yoga and other classes are also beginning to provide services virtually, she pointed out.
Data from China
A report published February 14 in the Lancet Oncology appears to be the first analysis in the literature to focus on COVID-19 in patients with cancer.
“Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery,” write the authors, led by Wenhua Liang, MD, of Guangzhou Medical University. However, in correspondence published in the Lancet Oncology, other experts in China question some of Liang’s and colleagues’ findings.
The report by Liang and colleagues concerns a prospective cohort of 1590 patients with COVID-19.
There were 2007 laboratory-confirmed cases of COVID-19 among patients admitted to 575 hospitals throughout China as of January 31. Of those cases, 417 were excluded from the analysis because of insufficient information regarding disease history.
The team reports that of 18 patients with cancer and COVID-19, 39% were at significantly higher risk for “severe events.” By comparison, of 1572 patients with COVID-19 who did not have cancer, 8% were at significantly higher risk (P = .0003). These events included rapid clinical deterioration that required admission to intensive care; invasive ventilation; or death.
Patients with cancer experienced a much more rapid deterioration in clinical status than did those without cancer. The median time to severe events was 13 days, vs 43 days (hazard ratio [HR] adjusted for age, 3.56; P < .0001).
The analysis also shows that patients who underwent chemotherapy or surgery in the past month had a 75% risk of experiencing clinically severe events, compared with a 43% risk for those who had not received recent treatment.
After adjusting for other risk factors, including age and smoking history, older age was the only risk factor for severe events (odds ratio [OR], 1.43; 95% confidence interval [CI], 0.97 – 2.12; P = .072), the study authors say.
Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (20% vs 62%, respectively; P = .294).
Liang and colleagues conclude that these findings provide “a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration.”
The team also proposes three strategies for managing patients with cancer who are at risk for COVID-19 or any other severe infectious disease. They recommend that intentional postponement of adjuvant chemotherapy or elective surgery be considered for patients with stable cancer who live in areas where disease is endemic. Stronger “personal protection provisions” could also be made for patients with cancer or for cancer survivors. Lastly, for patients with cancer who have COVID-19, especially those who are older or who have comorbidities, more intensive surveillance or treatment should be considered.
However, in comments in the Lancet Oncology, other authors in China say these findings should be interpreted with caution.
One group suggests that the increased susceptibility to COVID-19 in patients with cancer could be the result of higher rates of smoking compared with patients who did not have cancer. “Overall, current evidence remains insufficient to explain a conclusive association between cancer and COVID-19,” say Huahao Shen, PhD, of Zhejiang University School of Medicine, Hangzhou, Zhejiang, and colleagues.
Another group suggests that the significantly higher median age of patients with cancer compared with noncancer patients (63 years vs 49 years) may have contributed to poor prognosis.
These authors, led by Li Zhang, MD, PhD, and Hanping Wang, MD, of Peking Union Medical College and the Chinese Academy of Medical Sciences, Beijing, emphasize that patients with cancer need online medical counseling and that critical cases need to be identified and treated.
“In endemic areas outside Wuhan, decisions on whether or not to postpone cancer treatment need to made on a patient-by-patient basis and according to the risk to the patient and the prevailing situation because delays could lead to tumor progression and ultimately poorer outcomes,” they write.
The study was funded by the China National Science Foundation and the Key Project of Guangzhou Scientific Research Project. Liang and coauthors, Shen and coauthors, Zhang, Wang, and Smith have disclosed no relevant financial relationships. Markham has relationships with Aduro Biotech, Lilly, Tesaro, Novartis, and VBL Therapeutics.
This article first appeared on Medscape.com.