© 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...

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the αβ T-cell receptor and the remaining T-cells express the γδ T-cell receptor. As αβ T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts. The majority of γδ T-cells in the grafts expressed Vδ2 and/or Vγ9. Most patients receiving αβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study.

Our study highlights the importance of further exploration of graft composition before CB transplantation as a tool for risk prediction.

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