Systematic review and meta‐analysis of post‐transplant lymphoproliferative disorder in lung transplant recipients

Abstract

A systematic review of papers in English on post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random-effects model, and heterogeneity among studies was quantitated using I values. Fourteen studies published from 2005 to 2015 were included in the meta-analysis. One hundred and sixty-four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67-fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98-29.70; P = .003). pOR of death for early onset PTLD (<1 year post-LT) vs late onset (>1 year post-LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20-1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI -0.48-0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08-2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31-3.52, P = .94). This meta-analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.

Malignancy after lung transplantation

“…The incidence of PTLD after lung transplantation has been reported to be between 3-9% and is associated with worse long-term survival and high mortality (78,79).…”

“…In contrast, late onset PTLD, is seen more commonly in extrathoracic locations (e.g., intestinal tract and lymph node tissue) is disseminated and more likely to be an EBV negative tumor. Late-onset PTLD is generally associated with worse prognosis (73,78,79,84).…”

“…Rituximab binding to these cells induces cell death. Response rates have ranged between 44-66% in various studies and rituximab may be used in isolation, in conjunction with immunosuppression reduction or in combination with more traditional cytotoxic chemotherapeutic agents (73,79,87). More recently, there has been interest in developing targeted immunotherapies to treat PTLD.…”

“…However, confounding factors such as age, indication for transplantation, severity of pre-transplant illness, frailty, intensity of immunosuppression could not be adjusted for. Thus, further study is needed to determine if double lung transplantation is independently associated with a survival advantage in patients with PTLD (79).…”

Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival

“…Existing literature surrounding risk factors for PTLD in LTRs is limited. While EBV mismatch has been well established, retrospective study and meta‐analysis findings suggesting risk in association with age, cystic fibrosis, and race have demonstrated conflicting results . Importantly, IPF was the only end‐stage lung diagnosis found to be a risk factor for the development of PTLD irrespective of age.…”