Guidelines

COVID-19: ASTCT provides interim guidelines for transplantation

View on the News

Dealing with 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.

Dr. Zainab Shahid of University of North Carolina-Chapel Hill

Dr. Zainab Shahid

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.


 

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].”

Recommended Reading

Several factors may drive recent improvements in allo-HCT outcomes
MDedge Hematology and Oncology
CAR T-cell therapy may worsen mental health in some patients
MDedge Hematology and Oncology
Survival for older AML patients better with HSCT from unrelated donors
MDedge Hematology and Oncology
Safer CAR uses modified NK cells for advanced CLL, NHL
MDedge Hematology and Oncology
No reduction in oral mucositis with folinic acid post transplant
MDedge Hematology and Oncology
Stored CD34 cells for multiple myeloma patients largely unused
MDedge Hematology and Oncology
HIV free 30 months after stem cell transplant, is the London patient cured?
MDedge Hematology and Oncology
Younger children can safely visit HSCT recipients (sometimes)
MDedge Hematology and Oncology
NMA haploidentical allo-BMT plus post-transplant cyclophosphamide deemed safe, effective for CLL
MDedge Hematology and Oncology
Second transplant a good salvage option for children with ALL, AML, or MDS
MDedge Hematology and Oncology