Background The thymus produces T-cells which help fight infections. Infants without a conditioning thymus have athymia, commonly associated with complete DiGeorge syndrome (cDGS). Due to the lack of functioning T-cells, these infants are likely to die within the first two years of life unless the problem can be corrected.¹

A 6-month-old patient from Spain, with congenital athymia in the context of cDGS secondary to FOXI3 haploinsufficiency was admitted for thymus transplantation. The patient has Omenn’s syndrome (erythroderma, lymphadenopathies, eosinophilia and oligoclonal T-cells expansions), facial dysmorphism, primary hypoparathyroidism, mild left hydronephrosis, but no significant cardiac defects. Ciclosporin was commenced pre-transplant for Omenn’s due to the recurrence of a skin rash on the cessation of topical steroids. The patient was given three doses of rabbit anti-thymocyte globulin (ATG), Genzyme, with methylprednisolone as conditioning on day-3 to day-1 prior to transplant day (day 0). Intravenous calcium infusion was commenced whilst receiving ATG and was gradually tapered and switched to oral calcium supplements, with concomitant alfacalcidol and colecalciferol. Incisions were made on left and right anterior thighs on day 0, where 17 fresh thymus tissues were transplanted into each thigh, with no complications. Oral prednisolone was started on day 0 and weaned over five days. Patient was discharged on day+19.

Pharmacy contributions As the Trust is one of only two centres in the world that performs thymus transplants, patients travel globally for this procedure, adding to the challenge in obtaining accurate drug histories and providing appropriate counselling to patients/families. cDGS patients are prone to hypocalcaemia, especially after conditioning and transplant procedure, which can precipitate seizures. Understanding the calcium management plan prior to transfer and undertaking medicines reconciliation on arrival helps pharmacists formulate and tailor the transplant protocol. Circulating oligoclonal T-cells in patients with Omenn’s can cause graft-versus-host disease-like complications post-conditioning.² Pharmacists’ expert understanding of patient’s immunology blood workup prior to transplant supports the discussion of immunosuppressants requirements pre-, peri- and post-transplant.

To minimise risk, the protocol was developed and reviewed in a multidisciplinary approach. Each protocol addresses patients’ pre-existing comorbidities, preferences, and crucial monitoring such as viral screens, calcium monitoring and steroid tapering plan. It also contains supportive therapy, such as immunoglobulin and fungal prophylaxis, along with their therapeutic drug monitoring plan.

Outcome No flare of Omenn’s syndrome or complications arose. A thymus biopsy was carried out three months post-transplant, where there was evidence of well-formed thymic tissue with established thymopoiesis. The patient was well, and parents did not have any health concerns. Immunophenotyping will be evaluated six months post-transplant.

Lessons learned Thymus transplant is a high-risk procedure requiring a detailed management plan. Establishing good working relationships with the referring and medical team enables pharmacists to plan prior to transfer of care, ensuring existing therapies and doses are transcribed and/or switched to a UK-equivalent to stabilise the patient prior to transplant. Pharmacy team’s expert pharmaceutical knowledge and understanding of disease progression, together with good communication skills plays a vital role. ~75% of cDGS patients had been reported to have a successful outcome post-thymus transplant.¹

References

1. Great Ormond Street Hospital. 50th patient treated with thymus transplant at GOSH. April 2021. https://www.gosh.nhs.uk/news/50th-patient-treated-thymus-transplant-gosh (Accessed 26 June 2023).

2. Immune Deficiency Foundation. SCID Compass. Monitoring chimerism after BMT is critical to good health. April 2023. https://primaryimmune.org/resources/news-articles/monitoring-chimerism-after-transplant-critical-good-health (Accessed 03 July 2023).