Post-Transplant Lymphoproliferative Disorders (PTLDs) After Heart Transplantation: Single Center Experience in Japan
TRANSPLANTATION(2018)
Abstract
Objective Post-transplant lymphoproliferative disorders (PTLDs) are one of most important cause of morbidity and mortality after heart transplantation (HTx), especially in children. Although Rituximab therapy combined with chemotherapy and reduced immunosuppression has been reported to be effective to suppress B cell type PTLD (B-PTLD), PTLDs relapse frequently and the outcome is still poor. Everolimus (EVL) has been reported to inhibit growth of human EBV-transformed B lymphocytes in vitro and in vivo. In this report, we described 4 adults and 4 children of PTLD after HTx. Material and Methods All 8 cases were suffered from B-PTLD and one concomitantly had leiomyoma. Duration between HTx and onset of PTLD in children was shorter than that in adults [a mean 20.0 (6 to 38) months vs 65.5 (18 to 104) months]. In all patients, final diagnosis was made by histological examination (lymph nodes in 4, tumors in 3 and ulcer in 1). All patients received calcineurin inhibitor (CNI) (cyclosporine in 3 and tacrolimus in 5) and 7 received mycophenolate mofetil and one received EVL prior to PTLD. Results All 4 children and 3 adult showed elevation of Epstein Barr virus (EBV) DNA. In children, chief complaints were fever and/or abdominal pain, but no adults showed abdominal pain. All patients were given Rituximab and chemotherapy with reduced. EVL was started to be given after chemotherapy to keep a trough level within 3-8 ng/ml. A girl showed relapse of PTLD in the trachea, but she was cured after Rituximab treatment and withdrawal of CNI. One adult showed relapse of T-PTLD 7 years after the onset of B-PTLD. One adult shoed relapse of PTLD in the chest and died 15 months after the onset of PTLD. One boy showed complete remission of B-PTLD but still had multiple leiomyoma in the intestine. Other 4 patients showed no relapse. Conclusion All patients had B-PTLD but showed different histology and clinical findings. Most patients were associated with EBV and combination therapy with Rituximab may be useful. However, to manage PTLD, individual strategy might be required, and histological examination is essential to decide treatment strategy. the Practical Research Project for Allergic Diseases and Immunology (Research on Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED (Grant No. 17ek0510017h0002).
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Key words
Post-Transplant Lymphoproliferative Disease
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