• Dr. Vijay Ramanan

HSCT GUIDELINES – COVID PANDEMIC

EBMT GUIDELINES 2020- SUMMARY

COVID-19: Time from exposure to symptom development is between 2-14 days (median 5 days). Symptoms vary from no or very mild symptoms of an upper respiratory infection to very severe resulting in the need for intensive care and death from Acute Respiratory Distress Syndrome (ARDS).


Prevention policies and procedures: National, local and institutional guidelines should be followed. Avoiding exposure by adhering to recommended hygiene procedures, isolation of SARS-CoV-2 infected persons and social distancing are the only prevention strategies (see: The WHO recommendations).

Transplant centers: Visitors should be restricted as much as possible to transplant floors. Staff with respiratory symptoms should stay at home. Testing of staff should be done according to national and local guidelines. In the setting of known high community prevalence of SARS-CoV-2, clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible. Training of staff in proper procedures is critical.

Scheduling transplant procedures. Non-urgent transplants should be deferred as much as possible. Due to the rapidly changing situation, access to a stem cell donor might be restricted either due to the donor becoming infected, logistical reasons at the harvest centers in the middle of a strained health care system, or travel restrictions across international borders. 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 back-up. 2

Recommendation transplant candidates:

1. Patients planned to be admitted for a transplant should try to minimize the risk by home isolation 14 days before the start of the transplant conditioning. Non-necessary clinic visits should be avoided.

2. All patients should be tested for SARS-CoV-2 and the test results should be negative before start of the conditioning regardless of whether upper respiratory symptoms are present.

3. If a transplant candidate/patient is diagnosed with COVID-19, patients ought to be deferred for at least three months according to ECDC recommendations. However, this is not always possible due to the risk from the underlying disease. Therefore, in patients with high risk disease, HCT should be deferred until the patient is asymptomatic and has two repeated virus PCR negativity at least one week apart (deferral of 14 days minimum). In patients with low risk disease a three-month HCT deferral is recommended.

4. In case of close contact with a person diagnosed with COVID-19 any transplant procedures (PBSC mobilization, BM harvest, conditioning) shall not be performed within at least 14 preferably 21, days from the last contact. Patient should be closely monitored for the presence of COVID-19, with confirmed PCR negativity before any transplant procedure is undertaken.

Recommendations donors: SARS-CoV and MERS-CoV have been detected in blood, although there have not been any reports of transmission from donor to recipient either in transfusion of blood products or cellular therapies.

1. In case of diagnosis of COVID-19, donor must be excluded from donation. At this time it is not possible to give recommendations when such an individual can be cleared for donation but at least three months deferral can be considered unless the need for donation is urgent when individual consideration should be made.

2. In case of close contact with a person diagnosed with SARS-CoV-2, the donor shall be excluded from donation for at least 28 days. Donor should be closely monitored for the presence of COVID-19.

3. If the patient’s need for transplant is urgent, the donor is completely well, a test is negative for SARS-CoV-2 and there are no suitable alternative donors, earlier collection may be considered subject to careful risk assessment if local quarantine requirements permit.

4. In case of travel to high risk areas for COVID-19 (as defined by health authorities) or being a close contact with person travelling from such an area, donor shall be excluded from donation for at least 28 days.

5. Donors within 28 days before donation should practice good hygiene (see: Box 1. The WHO recommendations) and avoid crowded places and large group gatherings.

Recommendations stem cell transplant recipients:

1. Stem cell transplanted patients should restrict their risk of exposure to infected individuals as much as possible and to be very careful with hygienic routines including hand washing and use of alcohol containing hand sanitizers.

2. Stem cell transplant patients should refrain from travel according to national guidelines and if travel is absolutely necessary, travel by private car instead of train, bus, or plane is recommended if feasible. 3

3. Diagnostic procedures should be according to national guidelines. Patients, who reside in an area with high risk of transmission of SARS-CoV-2 or who have been in close contact to a person to such areas should be tested for the virus. It is important to note that a test for SARS-CoV-2 can be false negative and needs to be repeated if there is a strong suspicion of COVID-19 such is case of pneumonia or severe illness. It is also important to test for other respiratory viral pathogens including influenza and RSV preferably by multiplex PCR.

4. All patients positive for SARS-CoV-2 in an upper respiratory tract sample should undergo chest imaging preferably by CT and evaluation of oxygenation impairment.

5. Routine bronchoalveolar lavage (BAL) is not recommended if patient tested positive with SARS-CoV-2 given risk of transmission amongst health care workers, unless a co-infection is suspected. If chest imaging abnormal and in patients for whom it is clinically indicated (e.g., those receiving invasive mechanical ventilation), a lower respiratory tract aspirate or BAL sample should be collected and tested for SARSCoV-2. Co-pathogens should be evaluated and treated.

Treatment:

Currently there is no approved treatment options in India and there is no available vaccine.

Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) Revised Guidelines on Clinical Management of COVID – 19. 31ST MARCH 2020. No specific antivirals have been proven to be effective as per currently available data.

However, based on the available information (uncontrolled clinical trials), the following drugs may be considered as an off – label indication in patients with severe disease and requiring ICU management: • Hydroxychloroquine (Dose 400mg BD – for 1 day followed by 200mg BD for 4 days) In combination with • Azithromycin (500 mg OD for 5 days) These drugs should be administered under close medical supervision, with monitoring for side effects including QTc interval.

In case of diagnosis of COVID-19 infection:

1. It is unclear if patients with no/ mild u pper respiratory symptoms benefit from therapy.

2. In patients with progressing symptoms or lower respiratory tract symptoms, the possibilities of installing therapy should be investigated with participation in a clinical trial recommended if possible. The best data currently exist for chloroquine/hydroxychloroquine with increasing experience of use from several centers. Combination therapy has also been used. Revdesivir has been used as compassionate therapy in more severe cases.

3. Antinflammatory therapy can be considered in more severe cases.

4. Treatment for viral, bacterial, and fungal co-pathogens should be optimized.


The WHO recommendations on how to protect yourself and the others from COVID-19

1. Wash your hands frequently with an alcohol-based hand rub or with soap and water.

2. Maintain social distancing of at least 1 meter between yourself and anyone who is coughing or sneezing.

3. Avoid touching eyes, nose and mouth.

4. Practice respiratory hygiene (covering your mouth and nose with your bent elbow or tissue when you cough or sneeze and then dispose of the used tissue immediately).

5. If you have fever, cough and difficulty breathing, seek medical care early, but call in advance and follow the directions of your local health authority.

6. Stay informed and follow advice given by your healthcare provider, your national and local public health authority since they can provide you with reliable information on whether COVID-19 is spreading in your area.

7. Additionally, in case of persons who are in or have recently visited (past 14 days) areas where COVID-19 is spreading, stay at home if you begin to feel unwell, even with mild symptoms, until you recover, but if you develop fever, cough and difficulty breathing, seek medical advice promptly by calling your health provider to so you can be quickly directed to the right health facility.

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