Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation

Abstract

© F e r r a t a S t o r t i F o u n d a t i o norder to decrease the lag time for CTL transfer. Among other things, interferon-gamma capture of virus-specific CTL and allogeneic CTL banks containing CTL against the most common HLA haplotypes have been used with some success. 16,22,23 Our group has tried separation of peptide-specific T cells with the help of magnetic beads and MHC multimers. 17,18 Even though this has shown promising results, none of these strategies is yet part of standard clinical practice.In this retrospective analysis we analyzed possible risk factors associated with the development of PTLD after SCT at our center. The earlier part of the cohort of patients was previously included in the studies by Sundin et al. and Omar et al. 1,24 We found several factors that were independently associated with an increased risk of PTLD. Some of the factors seem to act synergistically, which adds additional risk of PTLD in the patients. Moreover, in spite of improved prophylaxis and rituximab use, the long-term survival of affected patients is poor. Methods PatientsIn total 1021 patients who underwent SCT at Karolinska University Hospital in Huddinge, Stockholm, between 1996 and 2011 were included in this retrospective analysis of risk factors for and clinical outcome of PTLD. This study was approved by the regional ethical committee in Stockholm (n. 425/97). A review of patients' charts and the clinical database identified 40 cases of verified PTLD. The characteristics of patients with and without PTLD are displayed in Table 1. Diagnosis and treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative diseaseThe diagnosis of PTLD was made according to the histological criteria reported for B-cell lymphoproliferative states following transplantation. 25 After July 2005 (total of 446 individuals) all patients considered to be at high risk of developing PTLD were screened weekly or biweekly for EBV during the first 3 months post-SCT. In patients at low risk, quantitative polymerase chain reaction (PCR) analysis was performed if EBV reactivation was suspected. From July 2005 all patients were treated with rituximab if the EBV load was >10 000 copies/mL. Thirty-five of the patients were treated with rituximab. More details are available in the Online Supplementary Methods section.Conditioning regimen, graft-versus-host disease prophylaxis and stem-cell source RIC was used in 402 patients, while myeloablative conditioning was given to 619 patients. Antithymocyte globulin (ATG) was given to 705 patients as part of the conditioning with the last dose on day -1. ATG was used in all patients with an unrelated or mismatched donor and in all patients with a non-malignant disease, independently of the type of donor. A few patients with a sibling donor treated with RIC (n=44) were also given ATG. The graft source was bone marrow in 361 cases, peripheral blood in 608 and umbilical cord blood in 52. For more details regarding conditioning regimens, GVHD prophylaxis and stem-cell source see th...

Impact of Epstein Barr virus-related complications after high-risk allo-SCT in the era of pre-emptive rituximab

“…This finding is consistent with prior studies reporting PTLD in 0-10% of transplant recipients. 18,[22][23][24] Even if the early introduction of Rituximab initially resolves this complication in most cases, a recent report by Uhlin et al 25 showed that only 20% of patients with PTLD were alive 3 years later. In our study, nine of the 13 patients suffering from this complication died between 4 and 445 days after diagnosis.…”

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

“…Risk factors for developing EBV-PTLD can be considered as existing pre- 20,24,[33][34][35] or developing post-transplant 7,[34][35][36][37] ( Table 3). Importantly, assessing the risk of EBV-PTLD is dependent on the HSCT context with potentially complex interactions between the primary hematological malignancy, HSCT procedure, source, and other factors.…”

Stromal cells–are they really useful for GVHD?

“…Co-infusion of BM-MSCs with cord blood transplantation delays immune reconstitution, as shown by lower levels of T-cell receptor excision circles and serum IgG and IgM. 21 It has further been found to be associated with the development of EBV-related post-transplant lymphoproliferative disorder, 9,22 and invasive fungal infections. 23 There are also worries that MSCs may promote cancer cell growth.…”