Document resource
Transplant Associated Thrombotic Microangiopathy (TA-TMA) is a syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenia caused by platelet clumping in the microcirculation and ultimately leads to organ injury. It is a frequently fatal complication post Bone Marrow Transplant (BMT) if not diagnosed or treated early, and it typically presents within the first 100 days. A prospective study covering 13 paediatric centres demonstrated a 19% incidence of TA-TMA in allogenic BMT recipients. 1 Clinical manifestations of this syndrome are wide-spread and depend on the organs affected; kidneys, central nervous system, cardiovascular system, gastrointestinal tract, skin, testes and polyserositis. The EBMT handbook, a key resource utilised across all JACIE-accredited BMT centres, suggests early diagnoses and treatment are essential to prevent organ injury and improve patient outcomes.2 However, approved treatment options remain exclusively supportive; transfusions, modifying immunosuppression, treating GvHD, infections, hypertension and optimising nutritional support. New agents with therapeutic targets that disrupt the underpinning mechanisms of TA-TMA (complement system and recipient or donor-specific ab anti-factor H antibodies) are unlicensed.3 Several targeted-treatments have been put forward for consideration in treating high-risk TA-TMA; eculizumab, narsopilmab, rituximab, defibrotide, ravulizumab, nomacopan, pegcetacoplan. Only the last three of which are currently in clinical trials.The ethical dilemma lies in that whilst there are no targeted-treatments approved for use across the NHS for TA-TMA, they are often accessed by individual NHS organisations via off-label or unlicensed formulary requests made on a patient-specific or a cohort basis. There are either funded by pharmaceutical companies offering compassionate use schemes or through hospital funding streams. This presents three ethical concerns; (a) treatments provided on free-of-change, compassionate use basis may be preferentially considered for formulary request applications over more expensive treatments as they may be more likely to be approved, (b) access to these treatments creates a postcode-lottery across NHS BMT centres as organisations can approve use of these treatments on a cohort basis, and (c) the unaccounted resources duplicated across the NHS in the preparation, evaluation and governance reviews of formulary applications that are processed in silos of individual hospitals for the same treatments used in the same indications.Lessons Learned There are several interventions pharmacy can make to address these dilemmas. These include; collaborating nationally to understand the extent of use of unlicensed and off-label targeted treatments for TA-TMA, collecting data on a national level and working with Pharma to support acquiring licenses for these treatments, and establishing a consensus on the preference and availability of treatments in different areas of the UK. This would allow for a proactive rather than reactive approach, encouraging cohort formulary applications in the first instance, and may be a cost-saving initiative through quantifying pharmacy resources spent on these governance processes. Whilst the NHS has multiple national treatment funding initiatives (i.e. policy propositions and innovative drug funds) for accessing novel treatments faster than full licensing processes, these still take too long for conditions such as TA- TMA, where paperwork and time taken to approve a targeted-treatment can make the difference between life and death.References Dandoy CE, Rotz S, Alonso PB, et al. A pragmatic multi-institutional approach to understanding transplant associated thrombotic microangiopathy after stem cell transplant. Blood Advances 2021;5:1–11.Sureda A, Corbacioglu S, Greco R, et al. The EBMT Handbook: Hematopoietic Cell Transplantation and Cellular Therapies. Springer. 2024;8th edition <https://doi.org/10.1007/978-3-031-44080-9> [Accessed 31 May 2025].Jodele S, Laskin BL, Dandoy CE, et al. A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Reviews 2015;29:191–204.