Abstract
Introduction: Post-transplant lymphoproliferative disease (PTLD) is an ultra-rare lymphoma following allogeneic hematopoietic stem cell transplant (HCT) or solid organ transplant (SOT). Incidence of PTLD varies over time after transplant with majority of cases occurring within the first year (yr) after HCT (Garcia-Cadenas, Eur J Haematol. 2019). In the SOT setting, PTLD can occur up to 30 yrs post-transplant and is largely dependent on the transplanted organ, the type and degree of immunosuppression, and transplant recipient characteristics (Dierickx, N Eng J Med. 2018; Trappe, J Clin Oncol. 2017). Published literature reports wide ranges of epidemiological estimates due to variation in the follow-up time, transplant type and sample size. We conducted a systematic literature review (SLR) to summarize the incidence of PTLD to better understand the reasons for such variation.
Methods: A SLR on the burden of PTLD was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines with the scope defined in terms of Population, Intervention Comparators, Outcomes and Study design (PICOS) criteria. Pertinent literature on epidemiology of PTLD published between January 2010 to February 2020 and relevant conference abstracts published between January 2018 to February 2020 were identified. Comprehensive literature searches were performed using the Ovid platform to identify articles indexed in PubMed, Embase, PsycINFO, and the National Health Service Economic Evaluation Database. Study designs were limited to population/registry-based studies, observational cohort studies (prospective/retrospective), and cross-sectional studies. Studies reporting incidence of PTLD were limited to those with at least 1000 total transplant recipients. All titles and abstracts were reviewed by two independent researchers with any discrepancies resolved by a third researcher. Incidence estimates were calculated by data extractors when it was not directly reported in the literature.
Results: A total of 177 studies reporting epidemiological data on PTLD were identified using pre-specified SLR criteria. Most of the studies (n=150) were retrospective in design. Incidence was reported in 114 studies. Majority of the studies reported cumulative incidence (CI) over specified times such as 5-yr or 10-yr incidence or proportion of patients (pts) with PTLD out of a sample of transplanted pts. In the HCT setting, only CI was reported; twelve studies reported CI ranging from 0.1% among 15094 pts receiving autologous HCT over a 19-yr period to 4% in a cohort of 1021 pts receiving allogeneic HCT over a 16-yr period. A total of 100 studies reported incidence of PTLD in SOT pts which was highly influenced by the study population, EBV status at the time of transplant and follow-up time. Of these, 12 reported incidence rates ranging from 24 EBV negative PTLD cases per 100,000 person-years (PY) within 1-5 yrs post-transplant to 3460 PTLD cases per 100,000 PY at 20 yrs post-transplant. Eighty studies reported CI, 19 of which reported CI for various timepoints. In a group of 23171 heart transplant pts CI was 1% during a median follow-up of 4.3 yrs, while in a subgroup of four pediatric multi-organ transplant recipients followed from 2003 to 2011 CI was 25%. Across studies, CI at 1-yr post-transplant ranged from 0.1% to 4.9% and 5-yr CI ranged from 0.7% to 12.1% in select group of transplant pts. Twenty-four studies reported CI by transplant organ type ranging from 0.2% in kidney transplant pts within the first year to 12.1% in lung transplant pts over 7.5 yrs, with higher estimates reported in studies with smaller sample sizes.
Conclusions: Our SLR shows large variation in the reported incidence of PTLD due to heterogeneity in the methodology and the study populations in both HCT and SOT settings. Published literature lacks the granularity to correctly interpret the incidence of PTLD in the general transplant population. Thus, additional methods and data considerations such as population type (HCT/SOT transplants, adult/pediatric pts, etc.), representativeness (single institutional data/multi-center/country level registry), unit of measurement of risk (CI/incidence rate, etc.), type of study (retrospective/prospective), length of follow-up, sample size, trends in transplant and treatment landscape over time are needed to ensure accuracy in the estimation of incidence of PTLD.
Disclosures
Thirumalai: Atara Biotherapeutics: Current Employment. Watson: Atara Biotherapeutics: Current Employment, Current holder of individual stocks in a privately-held company. Xun: Atara Biotherapeutics: Current Employment. Sadetsky: Atara Biotherapeutics: Current Employment. Schaible: Evidera: Current Employment. Barlev: Atara Biotherapeutics: Current Employment.
THE INDIVIDUAL TAILORING OF IMMUNOSUPPRESSIVE THERAPY AFTER HEART TRANSPLANTATION
