Successful treatment of Epstein-Barr virus-associated primary central nervous system lymphoma due to post-transplantation lymphoproliferative disorder, with ibrutinib and third-party Epstein-Barr virus-specific T cells.

Autor: Law SC; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Hoang T; Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.; Hue University of Medicine and Pharmacy, Hue, Vietnam., O'Rourke K; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Tobin JWD; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Gunawardana J; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Loo-Oey D; Proteomics Core Facility, Translational Research Institute, Woolloongabba, QLD, Australia., Bednarska K; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Merida de Long L; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Sabdia MB; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia., Hapgood G; Haematology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia., Blyth E; Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia., Clancy L; Cellular Therapies, NSW Government Health Pathology, Westmead, NSW, Australia., Hennig S; Certara Inc., Princeton, New Jersey.; School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany., Keane C; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.; Haematology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia., Gandhi MK; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.; Haematology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2021 Oct; Vol. 21 (10), pp. 3465-3471. Date of Electronic Publication: 2021 Jun 11.
DOI: 10.1111/ajt.16628
Abstrakt: Primary central nervous system lymphoma (PCNSL) occurring following organ transplantation (post-transplantation lymphoproliferative disorder [PTLD]) is a highly aggressive non-Hodgkin lymphoma. It is typically treated with high-dose methotrexate-based regimens. Outcomes are dismal and clinical trials are lacking. It is almost always Epstein-Barr virus (EBV) associated. Two patients (CA1-2) presented with EBV-associated PCNSL after renal transplant. CA1 was on hemodialysis and had prior disseminated cryptococcus and pseudomonas bronchiectasis, precluding treatment with methotrexate. CA2 was refractory to methotrexate. Both were treated off-label with the first-generation Bruton's tyrosine kinase inhibitor ibrutinib for 12 months. Cerebrospinal fluid penetration at therapeutic levels was confirmed in CA1 despite hemodialysis. Both patients entered remission by 2 months. Sequencing confirmed absence of genetic aberrations in human leukocyte antigen (HLA) class I/II and antigen-presentation/processing genes, indicating retention of the ability to present EBV-antigens. Between Weeks 10 and 13, they received third-party EBV-specific T cells for consolidation with no adverse effects. They remain in remission ≥34 months since therapy began. The strength of these findings led to an ongoing phase I study (ACTRN12618001541291).
(© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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