Explore the vast range of titles available.

The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% ( P <0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte–monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm ( P <0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted ( P <0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.

To evaluate the efficacy and safety of voriconazole in acute invasive aspergillosis (IA), an open, noncomparative multicenter study was conducted. Immunocompromised patients with IA were treated with intravenously administered voriconazole 6 mg/kg twice a day (b.i.d.) twice and then 3 mg/kg b.i.d. for 6-27 days, followed by 200 mg b.i.d. administered orally for up to 24 weeks. Response was assessed by clinical and radiographic change. A total of 116 patients were assessable. IA was proven in 48 (41%) and probable in 68 patients. Voriconazole was given as primary therapy in 60 (52%). Good responses were seen in 56 (48%); 16 (14%) showed complete response and 40 (34%) partial response. A stable response was seen in 24 patients (21%), and 36 (31%) of the infections failed to respond to therapy. Good responses were seen in 60% of those with pulmonary or tracheobronchial IA (n = 84), 16% with cerebral IA (n = 19), 58% with hematologic disorders (n = 67), and 26% of allogeneic stem cell transplant recipients (n = 23). Voriconazole is efficacious in treating acute IA.

To clarify the relationships between marginal zone lymphomas (MZLs) and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (WM/LPLs), immunoglobulin heavy chain variable gene ( IGHV ) features were analyzed and the occurrence of MYD88 L265P mutations was identified in a series of 123 patients: 53 MZLs from the spleen (SMZLs), 11 from lymph nodes (NMZLs), 28 mucosa-associated lymphatic tissue (MALT) lymphomas and 31 WM/LPLs. SMZLs were characterized by overrepresentation of IGHV1–2 gene rearrangements with a canonical motif, without selection pressure and with long CDR3 segments. NMZLs had increased frequencies of IGHV3 genes. The IGHV gene was unmutated in most cases, often with long CDR3 segments. MALT lymphomas were usually associated with a mutated IGHV gene, but with the absence of selection pressure. WM/LPLs were associated with an IGHV3–23 overrepresentation and high IGHV mutation rate, with features of selection pressure and short CDR3 segments. MYD88 L265P mutations were almost restricted exclusively to WM/LPL patients. Taken all diagnoses together, all patients with MYD88 L265P mutations had an immunoglobulin M peak and almost all patients except one had bone marrow infiltration. These results demonstrate that the history of antigen exposure of the four entities studied was different and MYD88 L265P was specifically associated with WM/LPLs. WM/LPL may thus be functionally associated with constitutive nuclear factor-κB activation.

Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity. We observed improvement in quality of life in 58 patients (97%). All parameters improved at 2 months. We observed significant differences at 2 months compared with baseline for the mean OSDI (86 versus 30, respectively, P <0.001), the mean Oxford score (3.2 versus 1.3, respectively, P <0.001) as well as visual acuity (Log MAR of 0.33 versus 0.10, respectively, P <0.001). Treatment with scleral lenses was discontinued in only 5 patients (8%) with a median follow-up of 20.5 months (range: 2–125 months). Scleral lenses were very efficient and well tolerated in patients with severe cGvHD-related KCS.

This study aimed to assess the impact of antithymocyte globulin (ATG) on patient outcome in a retrospective series of 91 patients (median age: 12 years) who underwent unrelated single-unit cord blood transplantation (allo-CBT) following a myeloablative conditioning regimen. Cord blood units were HLA-matched (6/6, n =18; 21%), one-Ag mismatched ( n =30, 35%) or two-Ag mismatched ( n =38; 44%). In this series, the OS, nonrelapse mortality (NRM) and cumulative incidence of relapse were 47±6%, 23±4% and 48±5%, respectively. Among 46 patients who received ATG as part of the conditioning regimen, the incidence of acute and chronic GVHD was lower than that in the group of 45 patients who did not receive ATG (20% vs 43%; P =0.03). However, multivariate statistical analysis revealed that the ATG use was associated with decreased OS and EFS rates and a high incidence of NRM (hazard ratio (HR)=1.99, 95% confidence interval (CI): 1.11–3.59, P =0.02), (HR=1.83, 95% CI: 1.08–3.10, P =0.02) and (HR=2.54, 95% CI: 1.03–6.26, P =0.04), respectively. Therefore, our results do not support the use of ATG as part of a myeloablative-conditioning regimen before single-unit allo-CBT in younger patients with hematological malignancies.

We investigated whether a young human leukocyte antigen (HLA)-matched unrelated donor (MUD) should be preferred as donor to an HLA-identical sibling (MRD) for older patients with myelodysplastic syndrome (MDS) (⩾50 years) who underwent allogeneic stem cell transplantation (AHSCT). Outcomes of 719 MDS patients with a median age of 58 years (range, 50–73 years) who received AHSCT from related ( n =555) or unrelated ( n =164) donors between 1999 and 2008 and reported to the European Group for Blood and Marrow Transplantation were analyzed. The median donor age of the MRD was 56 years (range: 35–78), in contrast to 34 years (range: 19–64) for the MUDs. Influence of donor’s age on survival was not observed for MRD (hazard ratio (HR): 1.01 (95% confidence interval (CI): 0.99–1.02), P =0.2), but there was a significant impact of MUD’s age on outcome (HR: 1.03 (95% CI: 1.01–1.06); P =0.02). Transplantation from younger MUDs (<30 years) had a significant improved 5-year overall survival in comparison with MRD and older MUDs (>30 years): 40% vs 33% vs 24% ( P =0.04). In a multivariate analysis, AHSCT from young MUD (<30 years) remained a significant factor for improved survival in comparison with MRD (HR: 0.65 (95% CI: 0.45–0.95), P =0.03), which should be considered in donor selection for older patients.

Non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (alloHSCT) can be predicted by the hematopoietic cell transplantation comorbidity index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score, which are composed of different parameters. We set out to integrate the parameters of both scores in patients with acute myeloid leukemia (AML) in first complete remission (CR1) receiving reduced intensity conditioning (RIC) alloHSCT. All parameters from the HCT-CI and the EBMT-score with the addition of patient and donor cytomegalovirus serology were evaluated in 812 patients by multivariable analysis with end-point NRM at 2 years. Subsequently, 16 parameters were selected based on hazard ratio >1.2, and were incorporated into a novel score, which was further internally validated by bootstrapping. Both the HCT-CI and the EBMT-score showed relatively weak predictive value, whereas the integrated score allowed to identify three clearly distinct risk groups with 2-year NRM estimates of 8±2% (low-risk), 17±2% (intermediate-risk) and 38±4% (high-risk), which also translated in prediction of overall survival. Collectively, integration of the most dominant parameters from the HCT-CI and the EBMT-score allowed to develop a simple and robust, integrated score with improved prediction of NRM for AML patients proceeding to RIC alloHSCT in CR1.

To describe outcomes, treatment and prognostic factors that influence survival of adult patients with acute lymphoblastic leukemia (ALL), who relapsed after allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed 465 ALL adult patients from European Group for Blood and Marrow Transplantation (EBMT) centers who relapsed after a first HCT performed in complete remission (CR1 65%, CR2/3 35%). Salvage treatments were: supportive care (13%), cytoreductive therapy (43%), donor lymphocyte infusion without or with prior chemotherapy (23%) and second HCT (20%). Median time from HCT to relapse was 6.9 months, median follow-up was 46 months and median survival after relapse was 5.5 months. Estimated 1-, 2- and 5-year post-relapse survival was 30±2%, 16±2% and 8±1%, respectively. In a multivariate analysis, adverse factors for survival were: late CR (CR2/3) at transplant ( P <0.012), early relapse after transplant (<6.9 months, P <0.0001) and peripheral blast percent at relapse ( P <0.0001). On the basis of multivariate model for survival, three groups of patients were identified with estimated 2 year survival of 6±2, 17±3 and 30±7%. Outcome of ALL patients relapsing after HCT is dismal and there is a need for new therapies. Our study provides the standard expectations in ALL relapse and may help in the decision of post-relapse therapy.

The objective of this registry study was to analyse the outcome of patients who underwent allogeneic or autologous haematopoietic stem cell transplantation (HSCT) for hepatosplenic T-cell lymphoma (HSTL), a rare and extremely aggressive peripheral T-cell lymphoma subtype. Patients were eligible if they had histologically verified HSTL and underwent HSCT between 2003 and 2011. Seventy-six patients were identified in the European Society for Bone and Marrow Transplantation database. Additional baseline and follow-up information could be obtained from the referring centres for 36 patients. Eleven of these were excluded following histopathology review, leaving 25 patients in the final study cohort (alloHSCT 18, autoHSCT 7). With a median follow-up of 36 months, 2 patients relapsed after alloHSCT, resulting in a 3-year progression-free survival of 48%. After autoHSCT, 5 patients relapsed and subsequently died. This study indicates that graft-versus-lymphoma activity conferred by alloHSCT can result in long-term survival for a substantial proportion of patients with HSTL.