Management of paediatric monomorphic post-transplant lymphoproliferative disorders with low-intensity treatment: A multicentre international experience

Pilar Guerra-García; Simon Bomken; Rebecca Ling; Arina Lazareva; Girish Gupte; Persis Amrolia; Mara Andrés; Jesús Diez-Sebastián; Mary M Taj

doi:10.1002/pbc.31053

Management of paediatric monomorphic post-transplant lymphoproliferative disorders with low-intensity treatment: A multicentre international experience

Pediatr Blood Cancer. 2024 May 16:e31053. doi: 10.1002/pbc.31053. Online ahead of print.

Authors

Pilar Guerra-García^{1

2}, Simon Bomken^{3

4}, Rebecca Ling⁵, Arina Lazareva⁶, Girish Gupte⁷, Persis Amrolia⁶, Mara Andrés⁸, Jesús Diez-Sebastián⁹, Mary M Taj¹⁰

Affiliations

¹ Paediatric Haematology and Oncology Department, University Hospital La Paz, Madrid, Spain.
² Translational Research in Paediatric Oncology, Haematopoietic Transplantation and Cell Therapy, University Hospital La Paz Institute for Health Research - IdiPAZ, Madrid, Spain.
³ The Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁴ Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
⁵ MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
⁶ Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, UK.
⁷ Liver Unit, Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham, UK.
⁸ Department of Paediatric Oncology, University Hospital La Fe, Valencia, Spain.
⁹ Epidemiology and Statistics, University Hospital La Paz, Madrid, Spain.
¹⁰ The Royal Marsden Hospital, Sutton, London, UK.

PMID: 38757407
DOI: 10.1002/pbc.31053

Abstract

Background: Monomorphic post-transplant lymphoproliferative disorder (mPTLD) is a major cause of morbidity/mortality following solid organ transplant (SOT), with infection, mPTLD progression and organ rejection presenting equal risks. Balancing these risks is challenging, and the intensity of therapy required by individual patients is not defined. Although an increasing body of evidence supports the use of a stepwise escalation of therapy through reduction in immunosuppression (RIS) to rituximab monotherapy and low-dose chemo-immunotherapy, many centres still use B-cell non-Hodgkin lymphoma (B-NHL) protocols, especially when managing Burkitt/Burkitt-like (BL) PTLD. This study sought to define outcomes for children managed in the UK or Spanish centres using low-intensity first-line treatments.

Procedure: Retrospective data were anonymously collected on patients younger than 18 years of age, with post-SOT mPTLD diagnosed between 2000 and 2020. Only patients given low-intensity treatment at initial diagnosis were included.

Results: Fifty-six patients were identified. Age range was 0.9-18 years (median 10.7). Most (62.5%) had early-onset PTLD. Haematopathological analysis showed 75% were diffuse large B-cell like, 14.3% were BL and nine of 33 (27%) harboured a MYC-rearrangement. Stage III-IV disease was present in 78.6%. All but one had RIS, 26 received rituximab monotherapy and 24 low-dose chemo-immunotherapy, mostly R-COP. Intensified B-NHL chemotherapy was required in 10/56 (17.9%). There were a total of 13 deaths in this cohort, three related to PTLD progression. The 1-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 92.8%, 78.6% and 80.2%, respectively.

Conclusions: R-COP provides an effective low-dose chemotherapy option. Escalation to more intensive therapies in the minority of inadequately controlled patients is an effective strategy.

Keywords: PTLD; low‐dose chemo‐immunotherapy; paediatric monomorphic PTLD; post‐transplant lymphoproliferative disorder.