The identification of patients at higher risk of developing Epstein-Barr virus (EBV) infection in hematopoietic stem cell transplants (HSCT) is useful for the prevention of EBV-associated diseases A prospective observational study was developed that included 40 patients (27 male and 13 females, with mean age of 32.2±1.5 years old) undergoing allogeneic-HSCT between January and December 2015. EBV was examined in whole blood samples collected during routine procedures at day (D)+30, D +60, +90, D+120, D+150 and D+180 post-transplant. EBV was detected, at least once during the follow-up period in 70.0% of our patients. Results indicated that patients with unrelated donors had increased risk of developing EBV infection at D+60 and D+150 (OR=3.9, P=0.058; OR=8.0, P=0.043; respectively). Moreover, myeloablative conditioning (OR=4.3, P=0.052), anti-thymocyte globulin use (OR=12.0, P=0.030) and graft-vs.-host disease (OR=6.7, P=0.032) were associated with EBV infection at D+60, D+150 and D+90, respectively. In our series, none of these patients developed post-transplant lymphoproliferative disease. To the best of our knowledge, the present study is the first study to report EBV infection in patients undergoing aHSCT from Portugal. The study revealed that EBV infection is associated with different factors. These findings provide evidence towards the identification of high-risk patients for EBV-infection and associated disease.

Post‑transplant lymphoproliferative disorder (PTLD), despite its rarity, is an important mortality/morbidity event in transplant patients. The purpose of the present study was to retrospectively examine the clinical and pathologic characteristics, and outcomes of PTLD at the Portuguese Oncology Institute of Porto. A retrospective review of patient information was performed for patients that developed PTLD following allogeneic hematopoietic stem cell transplant (aHSCT) and were diagnosed between 2005 and 2012. The present study included a total of 15 patients, 8 females (53.3%) and 7 males (46.7%), with different clinicopathological characteristics. The most frequent clinical condition inducing aHSCT was acute lymphocytic leukemia (40.0%). Conditioning regimens consisted primarily in busulfan and cyclophosphamide, with anti‑thymocyte globulin, and myeloablation was the preferential treatment. Epstein‑Barr virus (EBV) was present in all patients with a median time of diagnosis following transplant of 75 days (range, 25‑485 days) and a median viral load of 4.75 log10 copies/ml (range, 3.30‑6.26 log10 copies/ml). PTLD diagnosis was mainly assessed by clinical findings, and histological confirmation was available for 5 patients: 3 monomorphic, 1 polymorphic and 1 with early lesions of PTLD. To the best of our knowledge, this is the first study to describe PTLD cases in HSCT patients in Portugal. The data reinforces the importance of performing EBV monitoring in high‑risk patients, particularly those receiving a transplant from mismatch/unrelated donors, and those with myeloablative conditioning regimen including antithymocyte globulin. The results also suggested that EBV viral load may be significant for the prediction of PTLD development.

Introduction Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Underlying mechanisms are poorly known and usually multifactorial. Its treatment is not well defined, mostly based in platelet transfusion. Thus, is important to identify new strategies to manage this important post-SCT complication. Romiplostim and Eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Some studies with very small number of cases have reported their potential efficacy in the allo-SCT setting. For this reason, the aim of our study is to analyze the efficacy and safety of TPO-RAs for severe and persistent thrombocytopenia after allo-SCT. Patients and methods We performed a retrospective multicenter study including patients from centers of GETH with prolonged isolated thrombocytopenia (PT) or secondary failure of platelet recovery (SFPR) after allo-SCT. PT was defined as the engraftment of all peripheral blood cell lines but with platelet count ≤20000/µL for 7 consecutive days or requirement of transfusion for more than 60 days after allo-SCT. SFPR was defined as a decline of platelet counts to ≤20000/µL for 7 consecutive days or requirement of transfusion after achievement platelets ≥50000/µL without transfusion for 7 days post-SCT. The primary endpoint was platelet recovery to ≥50000/µL. Results Eighty-six patients with thrombocytopenia after allo-SCT were included. The characteristic of the patients, are summarized in table 1. Sixteen (19%) of the patients had PT and 71 (82%) SFPR. TPO-RA was started at a median time of 127 days (27-1177) after allo-SCT (41% Romiplostim / 59% Eltrombopag). Median initial and maximum administered doses were 50 mg/daily (25-150) and 75 (25-150) for Eltrombopag and 1 µg/kg (1-7) and 5 (1-10) for Romiplostin, respectively. Eighteen patients (21%) were previously treated with cell infusion (67% mesenchymal cells and 33% CD34+ boost). Median platelet count before TPO-RA onset was 14000/µL (1000-57000). Platelet recovery to ≥50000/µL was 60% and the response was achieved at a median time of 56 days (2-247). Responses were similar considering all potential causes of thrombocytopenia evaluated. 81% of the patients had decrease number of megakaryocytes prior to treatment showing a worse response to therapy: median time to ≥20000/µL platelets 43 days versus 28 days (p=0.011), with also a lower rate of platelet recovery to ≥50000/µL (62% versus 85% if normal megakaryocytes). In patients treated with Eltrombopag, 27% had neutropenia <1000/µL and 74% achieved >1000/µL after therapy. The median treatment duration was 62 days (7-700) and 62% discontinued TPO-Ra maintaining response. Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the cases. At last follow up with a median of 10 months (1-59), 72% of the patients maintained the response and 61 (71%) were alive. Death rate was significantly lower in responder-patients to TPO-RAs, 15% versus 53% in non-responders (p<0.001). Causes of death were disease progression (28%), infections (48%), graft versus host disease (GvHD) (16%) and others (8%). Conclusion To our knowledge this is the biggest series analyzing the use of TPO-Ra after allo-SCT. Our results support the efficacy and safety in this new setting with responses around 60% and a low number of side effects. Additional studies to identify predictors of response are needed. Disclosures No relevant conflicts of interest to declare.

OutcOmes Of allOgeneic stem cell transplantatiOn amOng patients with acute myelOid leukemia presenting active disease: experience Of a single eurOpean cOmprehensive cancer center rev assoC med bras 2016; 62 (7) Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) represents a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant--related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results:The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months ) and median PFS, 3 months (95CI 1.835-4.165). Conclusion:In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.

Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS) of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic lymphocytic leukemia (CLL). Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.