Study finds ‘strikingly’ high risk of post-transplant lymphoproliferative disease in some patients

A large analysis of post-transplant lymphoproliferative disease (PTLD) after solid organ transplant has found a high early incidence after multivisceral transplant and an ongoing risk of disease for many years.

Reporting in the British Journal of Haematology, the UK researchers who looked at a database of more than 5,000 patients who had received several different types of solid organ transplant, found a cumulative incidence of PTLD of 5.9%.

But there were stark differences in data by organ type. Cumulative incidence was 18% at five years after multivisceral transplant and 1%–3% at five years following the other solid organ types.

They also reported that after 20 years, cumulative incidence was 2%–3% following liver and heart transplantation and 10% after kidney transplantation.

Median overall survival after solid organ transplant was 16 years and there was also a relatively high early mortality after a diagnosis of PTLD, which only starts to approach the longer term survival of solid organ transplant recipients after two years, they reported.

The analysis also suggested that a risk-stratified approach with first-line rituximab monotherapy is “effective and safe in the real world as well as in clinical trials”.

But the results show there is a need for other low-toxicity PTLD treatments and for safe and effective pre-emptive strategies, they concluded, particularly around the therapies directed at the Epstein-Barr virus, they added.

The “strikingly high early incidence” of PTLD in multivisceral organ transplant recipients is consistent with the large volume of lymphoid tissue in the graft as well as the high immunosuppressive burden associated with treatment, they explained.

And the high long-term cumulative incidence of PTLD in those who had undergone kidney-transplant is likely because of the longer duration of triple therapy in low immunological risk patients and tacrolimus, mycophenolate mofetil and prednisolone in high immunological risk patients, they added.

Study leader Dr Anna Santarsieri, from the Department of Haematology at Addenbrooke’s Hospital in Cambridge, said this was the largest UK dataset looking at PTLD in solid organ transplant patients.

“It reports PTLD incidence in a wider range of transplant types than other studies due to the comprehensive nature of the solid-organ transplant programme on the Cambridge Biomedical Campus,” she said.

“The study shows a predominance of EBV-associated PTLD, particularly in multivisceral transplant patients.

“This gives potential for the future use of EBV-directed therapies for PTLD. It may also encourage the use of pre-emptive therapies to treat EBV viraemia before PTLD develops,” she told the limbic.

“Our real-world outcomes support a risk-stratified approach using first-line rituximab monotherapy for monomorphic PTLD, DLBCL.

“However, there remain a high proportion of patients dying from non-PTLD causes both pre and post-remission and there is a need for other low-toxicity PTLD treatments and for pre-emptive strategies,” she said.

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