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Haematopoietic stem cell transplantation: COVID-19 rapid guideline summary

This rapid NICE guideline (NG164) is designed to maximise the safety of patients who require haemopoietic stem cell transplantation (HSCT) as well as protecting staff and making the best use of NHS should services become limited due to COVID-19.

Patient communication
NG164 recognises the importance of communicating with patients to support their mental wellbeing during the pandemic and to help alleviate any anxieties or concerns that they might have about COVID-19. Patients requiring HSCT are likely to be immunosuppressed and clinics are required by the guidance to introduce measures to help minimise the potential for contracting or spreading COVID-19.

As an example, NG164 directs that healthcare staff minimise face-to-face patient contact and have telephone or video consultations. Non-essential follow-ups should be minimised and greater use made of home delivery services for medicines, or drive-through medicine pick-up points and that clinics coordinate access to blood tests for post-transplant investigations.

For essential clinic appointments, clinics are advised to ask patients to attend alone if possible and if not, with no more than one family member or carer. Patient wait times should be minimised through careful scheduling and patients discouraged from attending too early and to remain in their transport vehicle until sent a text message that they are ready to be seen at the clinic.

Patients known or suspected of having COVID-19
NG164 advises all staff (including those involved in receiving, assessing and caring) working with suspected or infected patients to follow the government infection and prevention control guidance.

Patients displaying new symptoms
NG164 suggests that clinics direct patients who feel unwell before an appointment, to contact their dedicated transplant programme helpline to ensure that symptoms are appropriately assessed. NG164 also reminds clinicians that immunosuppressed HSCT patients may display atypical COVID-19 symptoms although in those with a fever (with or without respiratory symptoms), neutropenic sepsis should be suspected. Because this condition can rapidly develop and is potentially life-threatening, NG164 advises that clinicians follow the NICE guideline on neutropenic sepsis and to immediately refer suspected cases to secondary or tertiary care and offer patients empiric antibiotic therapy.

If a patient is subsequently diagnosed with COVID-19 and not initially isolated, NG164 suggests that staff follow the current guidance for health professionals. Furthermore, where patients were not previously known to be infected develop new symptoms suggestive of COVID-19, staff are directed to follow guidance on investigation and initial clinical management which includes relevant information on testing and isolating patients.

Transplant recipients: pre-transplant guidance
Patients NOT known to have COVID-19
Solid organ transplant recipients are considered extremely vulnerable in the NHS shielding guidance and pre-transplant patients are advised to follow this guidance for at least two weeks before the procedure. Moreover, NG164 recommends that all patients are tested for respiratory viruses and COVID-19 at least once and 72 hours before their procedure. Further recent guidance on this topic has been produced by the British Society of Blood and Marrow Transplantation and Cellular therapy.

Autologous transplants
NG164 recommends deferral for all but exceptional cases of these transplants for myeloma, low-grade lymphoproliferative diseases and non-malignant indications and stresses that decisions should be made by a multidisciplinary team on an individual basis until the risks associated with the COVID-19 pandemic have passed.

Allogeneic transplant recipients
Equally, NG164 advises deferral for the majority of these transplants for any non-urgent indications and chronic haematological malignancies. Furthermore, NG164 instructs that allogeneic transplants should be deferred for three weeks if the recipient has been in close contact with an individual who has tested positive for COVID-19 within the last week.

Patients known or suspected of having COVID-19
NG164 advises testing patients for both COVID-19 and other respiratory viruses using the recent government guidance on investigation and initial clinical management of possible cases. This guidance directs that transplants are deferred by at least 3 months in those who test positive for COVID-19 except for patients who have a high risk of disease progression, morbidity or mortality.

However, for COVID-19 patients with a high risk of disease progression, NG164 advises that transplant is deferred until symptoms have resolved and they have at least three repeated negative PCR tests, conducted at least one week apart.

Transplant donors
Donors NOT known to have COVID-19
According to NG164, sibling donors should follow government social distance guidance for at least 4 weeks before donation and be fully informed of COVID-19 symptoms, the transmission risk and any related donation restrictions so that they are more likely to self-deter. Moreover, donation should be deferred for at least four weeks from the start of self-isolation.

For cryopreservation donations, NG164 advises testing for COVID-19 at the assessment and again at the harvest of stem cells or donor lymphocytes. If in exceptional circumstances, fresh cell donations are needed, NG164 recommends testing for COVID-19 at the assessment and again one or two days before starting conditioning.

Potential donors are advised to inform the coordinating registry and the collection centre at which they donated, if they develop any illness within two weeks after donating.

Donors known or suspected to have COVID-19
NG164 recommends that clinic staff defer donations by three months for infected or suspected infected patients from when symptoms have resolved.

If the HSCT is urgent and where there are no suitable donor available, NG164 suggests clinical staff assess the risk and liaise with the registry and explore alternative sources of haematopoietic stem cells, for example, HLA mismatched (haplo-identical) family members and cord blood. These alternatives should be discussed with the recipient and they should be kept fully informed of the donor situation.

NG164 also states that suspected or infected donors should not provide other blood products (and this includes lymphocytes) for at least three months from when their symptoms resolve.

Transplant recipients: post-transplant
All transplant patients are to be managed in a strict and protective isolated environment. If procedure is required outside isolation, staff should assess the risk against the risk of exposing the patient to COVID-19 exposure. As mentioned earlier, NG164 also advises that transplant patients follow the government shielding guidance until the risks associated with COVID-19 have passed.
This advice pertains to the following recipients:

• those who have had autologous transplants within last 12 months
• those who have had allogeneic transplants with the last TWO years
• if they are having continuous immunosuppressive therapy, they have chronic graft versus host disease or if there is evidence of any on-going immunodeficiency or if they meet the criteria for any other extremely vulnerable groups after clinical assessment

For COVID-19 patients, NG164 advises that they are isolated in negative pressure cubicles or alternatively neutral pressure cubicles.

Supporting staff and those who have self-isolated
NG164 suggests how staff working with transplant patients and who need to self-isolate can continue to work, if possible. This might include video or telephone consultations, attending virtual multidisciplinary team meetings and roles such as identification of patients suitable for remote monitoring or the more vulnerable and routine work, for example, data entry.

COVID-19 positive staff are advised not return to direct work with transplant patients until they no symptoms for seven days and test negative for COVID-19 but can work in other clinical areas after self-isolation, provided they follow the government advice on households with possible COVID-19 infections.

During the pandemic, NG164 recommends that there is visible leadership within transplant departments and supportive messaging to staff in an effort to maintain morale. Furthermore, during these difficult times staff should utilise the principles of good partnership working when developing local plans.

How to prioritise HSCT
The table was developed to help clinicians assess the risks and benefits for patients having HSCT. NG164 recommends the use of this table but reminds clinicians to use a case-by-case approach to balance of risks from patient’s disease compared to the post-transplant risk of becoming seriously ill from COVID-19, the potential for critical care support and disease relapse and finally any service capacity issues.

The table is based on advice provided by the British Society of Blood and Marrow Transplantation and Cellular therapy guidance.

NG164 suggests clinicians consider using transplant outcome predictive tools such as the refined disease risk index and the haematopoietic cell transplantation-comorbidity index where these are appropriate to aid with the decision-making process but also to be mindful of the limitations of these tools.

Modification to usual service provision
NG164 advises clinical teams to review usual care with a view to making best use of resources, reducing patient exposure to the virus and assessing capacity across the region. Teams are also advised to work within clinical networks to support stem cell processing and harvesting, specialised diagnostic and cryopreservation. Furthermore, all cases of COVID-19 should be reported to the European Society for Blood and Marrow transplantation prospective survey.

Another important aspect of service modification highlighted by NG164 is the need for extra vigilance with respect to quality management systems within the HSCT programme and JACIE accreditation requirements. Where a centre cannot meet these requirements, NG164 advises that temporary closure should be considered as an option.

However, if a centre does close, staff need to liaise within the clinical network to prioritise any urgent cases (see table) and for patients having allogeneic HSCT, a backup donor should be identified or blood cord unit just in case there are any problems with harvesting or transport. In addition, if a donor tests positive for COVID-19, their cells should be moved to a marker-positive tanks unless they are to be used within four weeks.

For paediatric patients, NG164 advises that clinical staff follow the advice from the Paed BMT group.

The HSCT guideline is available online and interested readers should check for any relevant updates.