Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation

Abstract

We evaluated 26 901 patients who underwent allogeneic hematopoietic cell transplantation (HCT) at 271 centers worldwide to define patterns of posttransplantation lymphoproliferative disorders (PTLDs). PTLDs developed in 127 recipients, with 105 (83%) cases occurring within 1 year after transplantation. In multivariate analyses, we confirmed that PTLD risks were strongly associated (P < .001) with T-cell depletion of the donor marrow, antithymocyte globulin (ATG) use, and unrelated or HLA-mismatched grafts (URD/HLA mismatch). Significant associations were also confirmed for acute and chronic graftversus-host disease. The increased risk associated with URD/HLA-mismatched donors (RR ‫؍‬ 3.8) was limited to patients with T-cell depletion or ATG use (P ‫؍‬ .004). New findings were elevated risks for age 50 years or older at transplantation (RR ‫؍‬ 5.1; P < .001) and second transplantation (RR ‫؍‬ 3.5; P < .001). Lower risks were found for T-cell depletion methods that remove both T and B cells (alemtuzumab and elutriation, RR ‫؍‬ 3.1; P ‫؍‬ .025) compared with other methods (RR ‫؍‬ 9.4; P ‫؍‬ .005 for difference). The cumulative incidence of PTLDs was low (0.2%) among 21 686 patients with no major risk factors, but increased to 1.1%, 3.6%, and 8.1% with 1, 2, and more than 3 major risk factors, respectively. Our findings identify subgroups of patients who underwent allogeneic HCT at elevated risk of PTLDs for whom prospective monitoring of Epstein-Barr virus activation and early treatment intervention may be particularly beneficial. (Blood. 2009;113: 4992-5001)

Epstein–Barr virus microRNAs reduce immune surveillance by virus-specific CD8 + T cells

“…For immunosuppressed patients, it appears clear that T-cell deficiency favors appearance of latency III malignancies (3), that adoptive T-cell therapy can prevent this (4,5), and that T-cell therapy fails if the EBV strain in question does not express crucial CD8 + T-cell epitopes in a latency III protein (50). Regarding infection in immunocompetent carriers, there were early arguments against a T-cell surveillance of latency III (51), but later studies showed that latency III-associated CD8 + T-cell epitopes are in fact under a selective pressure that depends on the frequency of HLA class I allotypes in a population (52,53).…”

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

“…In an international study of 26,901 allogeneic HCT recipients during 1964–1994, the observed to expected ratio of PTLD was 29.7. 13,80 MDS/AML risk after allogeneic HCT is thought to be comparable to that of other cancer survivors who have received particular cytotoxic chemotherapeutic agents and radiotherapy, with such risks often exceeding 10-fold. 81 There is also some evidence that MDS/AML risks may be even higher after autologous HCT because of the substantial cumulative doses received during pre-transplant chemotherapy and radiotherapy, chemotherapy-based stem cell mobilization and HCT conditioning.…”

“…For example, immune activation or chronic immune damage of tissues from GVHD could act synergistically with viruses to impact risk of cancers such as oral cavity SCC. 80,172–175 Similarly, immunosuppression could lead to the reappearance of latent HPV infection, affecting risk of cutaneous SCC or cervical cancer. 176,177 …”

EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT

“…2,3 Published experience regarding the incidence of EBV-PTLD after allogeneic HCT ranges between 0.5 and 17% and is mainly based on single-centre experiences or retrospective studies limited by small numbers and diverse patient characteristics. [4][5][6][7] However, Landgren et al 8 collected data on 127 EBV-PTLD cases from 271 centres and found an elevated risk for developing PTLD especially in the first year after HCT (83%) with the highest occurrence during the first 6 months. However, late EBV-PTLD could be observed even up to 10 years after HCT.…”