Explore the vast range of titles available.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age ( P =0.028), unrelated donor ( P =0.0178), stem cell source ( P =0.0001), HLA mismatching ( P =0.0022) and BU in conditioning regimen ( P =0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) ( P =0.0005) and peripheral blood stem cells ( P =0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity ( P =0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization ( P <0.0001), more RBC ( P =0.0003) and platelet transfusions ( P <0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at €2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6–19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells ( P =0.0021), in patients with a one mismatched donor ( P =0.041) and in patients who had received ATG in the conditioning regimen ( P =0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

We have conducted a retrospective study on 251 patients from three centers in France and Switzerland between 2004 and 2010 with the goal to evaluate the impact of HLA-DRB3/B4/B5 allele mismatching after HLA-10/10-matched unrelated allogeneic hematopoietic stem cell transplantation (HSCT). Fourteen (5.5%) patients receiving HSCT from an HLA-10/10-matched unrelated donor had a mismatched DRB4 donor, 23 (9.5%) patients had a mismatched DRB3 donor and 214 (85%) had a fully matched unrelated donor (HLA-10/10) without DRB3- or DRB4-mismatched donor. We compared the outcomes of 37 patients with a DRB3 or DRB4 mismatch with the rest of the population. The median survival for a patient without DRB3/4 mismatch was 18 months (95% confidence interval (CI), 13–29), for DRB3-mismatched patients 32 months (95% CI, 13-NR) and for DRB4-mismatched patients 7 months (95% CI, 3-NR). The multivariate analysis showed a significant impact of DRB4 mismatching on survival (Hazards ratio (HR)=2.1 (95% CI, 1.01–4.67), P =0.045), acute GvHD (HR=2.66 (95% CI, 0.99–7.09) P =0.05) and on transplant-related mortality (HR=2.8; (95% CI, 1.7−4.4) P =0.024). In the view of an impact of DRB4 locus mismatch on clinical outcome, it would be important to confirm this observation in a prospective study as it may be worth considering DRB4 in the unrelated donor selection.

The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO ( N   =  61) or MRD ( N   =  90) between January 2011 and January 2016. GRFS was defined as the probability of being alive without evidence of relapse, grade 3–4 acute GVHD or chronic GVHD. In multivariable analysis, MRD donors were independently associated with lower GRFS compared to HAPLO donors (HR  =  2.95, P    < 0.001). Disease status at transplant other than CR was also associated with lower GRFS in multivariable analysis (HR  =  1.74, P   =  0.01). In addition, the administration of ATG was independently linked to higher GRFS (HR  =  0.52, P   =  0.009). In summary, we observed significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT-Cy platform compared to MRD.

We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM‐TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow‐up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60.8 years, AML 62%, CR1 69%, median follow‐up: 22.4 months) RIC regimen. In multivariate analysis, FB2A2 was associated with significant lower overall survival (OS, HR: 2.14; 95%CI: 1.05–4.35, P = 0.04) and higher relapse incidence (RI, HR: 2.17; 95%CI: 1.02–4.61, P = 0.04) and a trend for lower leukemia‐free survival (LFS, HR: 1.75; 95%CI: 0.94–3.26, P = 0.08). These results were confirmed using a propensity score‐matching strategy. However, when considering AML and MDS patients separately, the benefit of the CLOB2A2 regimen was restricted to AML patients (2‐year OS FB2A2: 38% [14.5–61.6] vs. CloB2A2: 79.2% [62.9–95.4], P = 0.01; 2‐year LFS FB2A2: 38% [16–59.9] vs. CloB2A2: 70.8% [52.6–89], P = 0.03). The better survivals were due to the lower risk of relapse in this CloB2A2 AML subgroup (2‐year RI FB2A2: 41.2% [19–62.4] vs. CloB2A2: 16.7% [5–34.2], P = 0.05). This retrospective comparison suggests that the CloB2A2 RIC regimen can likely provide longer survival than that awarded by a FB2A2 RIC regimen and may become a new standard of care RIC regimen for allotransplanted AML patients. A prospective phase 3 randomized study is warranted. CloB2A2 RIC regimen provided better OS and leukemia‐free survival compared to the standard FB2A2 RIC regimen in allografted acute myeloid leukemia (AML) patients. The better survivals observed in the CloB2A2 AML subgroup was due to a lower risk of relapse, confirming the higher antileukemic activity of clofarabine versus fludarabine.

Modern cell biologists typically use reporter genes either alone or co-expressed with a protein of interest to facilitate the localization or quantification of protein expression. Our work demonstrates that reporter genes should be used cautiously, as several common reporter gene products are toxic to primary cortical neuronal cultures. We used the herpes simplex virus-based viral amplicon vector to transduce cortical neurons with three different reporter genes and assessed whether any reporter gene products were toxic over time, by monitoring neurite disintegration and apoptosis. Toxicity varied as a function of the reporter gene, the gene product localization, and the level of reporter gene expression. Transduction of enhanced green fluorescent protein or nuclear-localized β-galactosidase was more toxic than non-nuclear localized β-galactosidase. This work underscores the need for careful design of gene expression constructs. Moreover, in studies where cell injury or toxicity is being evaluated, their use should be carefully considered.