A Strategy for Studying Epigenetic Diversity in Natural Populations: Proof of Concept in Poplar and Oak.

These last 20 years, several techniques have been developed for quantifying DNA methylation, the most studied epigenetic marks in eukaryotes, including the gold standard method, whole-genome bisulphite sequencing (WGBS). WGBS quantifies genome-wide DNA methylation but has several inconveniences rendering it less suitable for population-scale epigenetic studies. The high cost of deep sequencing and the large amounts of data generated prompted us to seek an alternative approach. Restricting studies to parts of the genome would be a satisfactory alternative had there not been a major limitation: the need to select upstream targets corresponding to differentially methylated regions (DMRs) as targets. Given the need to study large numbers of samples, we propose a strategy for investigating DNA methylation variation in natural populations, considering the structural complexity of the genomes with their size and their content in unique as coding regions versus repeated regions as transposable elements. We first identified regions of highly variable DNA methylation in a representative subset of genotypes representative of the biological diversity in the population by WGBS. We then analysed the variations of DNA methylation in these targeted regions at the population level by Sequencing Capture Bisulphite (SeqCapBis). The entire strategy was then validated by applying it to another species. Our strategy was developed as a proof of concept on natural populations of two forest species: Populus nigra and Quercus petraea.

Postremission Consolidation by Autologous Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia in First Complete Remission (CR) and Negative Implications for Subsequent Allogeneic HCT in Second CR: A Study by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

After autologous hematopoietic cell transplantation (HCT) in the first complete remission (CR1), patients with acute myeloid leukemia (AML) may relapse and undergo allogeneic HCT in the second complete remission (CR2). The aim of this study was to analyze the outcome of allogeneic HCT performed in CR2 comparing patients with prior consolidation by autologous HCT versus patients with chemotherapy consolidation. Included were 2619 adults with allogeneic HCT in CR2 from 2000 to 2017 with (n = 417) or without (n = 2202) prior autologous HCT. Patient groups were not entirely comparable; patients with prior autologous HCT were younger, had less often a favorable cytogenetic profile, had more commonly donors other than matched siblings, and more often received reduced-intensity conditioning. In multivariate analysis, nonrelapse mortality risks in patients with prior autologous HCT were 1.34 (1.07 to 1.67; P = .01) after adjustment for age, cytogenetic risk, transplant year, donor, conditioning intensity, sex matching, interval diagnosis-relapse, and relapse-allogeneic HCT as compared with chemotherapy consolidation. Similarly, risks of events in leukemia-free survival and graft-versus-host disease, relapse-free survival were higher with prior autologous HCT, 1.17 (1.01 to 1.35), P = .03 and 1.18 (1.03 to 1.35), P = .02, respectively. Risk of death was also higher, 1.13 (0.97 to 1.32), P = .1, but this was not significant. Postremission consolidation with autologous HCT for AML in CR1 increases toxicity of subsequent allogeneic HCT in CR2.

Acidity of SiO2-Supported Metal Oxides in the Presence of H2O Using the AEIR Method: 2. Adsorption and Coadsorption of NH3 and H2O on TiO2/SiO2 Catalysts.

Two different TiO2/SiO2 compounds containing TiO2 nanodomains dispersed over SiO2 were investigated applying the AEIR method at the adsorption equilibrium of NH3 and H2O from 300 to 723 K, particularly for the measurement of the individual heats of adsorption of the different species on Lewis acidic sites (LAS) and Brønsted acidic sites (BAS) as evaluation of the strength of the sites. It revealed two types of NH3 adsorption sites: the first ones could correspond either to NH3 species H-bonded to free OH groups or to coordinated weak LAS (named L1). The second ones (L2) were attributed to strongest LAS similar to those present at the surface of TiO2 nanocrystallites. They also correspond to the stronger adsorption sites of H2O. Two types of Brønsted acid sites (BAS) were additionally evidenced by the AEIR method and proposed to be specifically located on the Si-O-Ti bridging bonds at the TiO2/SiO2 interface. The heats of adsorption of the different adsorbed species provided by the AEIR method were consistent with literature data on average values of the heats of adsorption of NH3 and H2O from microcalorimetry measurements. The surface acidity of the two compounds in the presence of H2O was determined using NH3-H2O coadsorption. At T ≥ 473 K, the NH3 species on the L2 sites were not significantly displaced from the surface whatever the partial pressure of H2O studied in agreement with the Temkin competitive model using the individual heats of adsorption of the NH3 and H2O species. This model also revealed the presence of a small amount of H2O species adsorbed on L2 sites allowing H2O dissociation or/and hydrolysis of SiOTi or TiOTi bridges, leading to the formation of a much higher amount of BAS. Therefore, this original work combining the AEIR method and the Temkin competitive model provided new insights for understanding water effects on acidic oxide catalysts.

Long-term fatigue and quality of life among epithelial ovarian cancer survivors: a GINECO case/control VIVROVAIRE I study.

BACKGROUND: Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. PATIENTS AND METHODS: EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. RESULTS: A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). CONCLUSION: Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Reactivity and structural evolution of urchin-like Co nanostructures under controlled environments.

In situ transmission electron microscopy (TEM) of samples in a controlled gas environment allows for the real time study of the dynamical changes in nanomaterials at high temperatures and pressures up to the ambient pressure (105 Pa) with a spatial resolution close to the atomic scale. In the field of catalysis, the implementation and quantitative use of in situ procedures are fundamental for a better understanding of the behaviour of catalysts in their environments and operating conditions. By using a microelectromechanical systems (MEMS)-based atmospheric gas cell, we have studied the thermal stability and the reactivity of crystalline cobalt nanostructures with initial 'urchin-like' morphologies sustained by native surface ligands that result from their synthesis reaction. We have evidenced various behaviors of the Co nanostructures that depend on the environment used during the observations. At high temperature under vacuum or in an inert atmosphere, the migration of Co atoms towards the core of the particles is activated and leads to the formation of carbon nanostructures using as a template the initial multipods morphology. In the case of reactive environments, for example, pure oxygen, our investigation allowed to directly monitor the voids formation through the Kirkendall effect. Once the nanostructures were oxidised, it was possible to reduce them back to the metallic phase using a dihydrogen flux. Under a pure hydrogen atmosphere, the sintering of the whole structure occurred, which illustrates the high reactivity of such structures as well as the fundamental role of the present ligands as morphology stabilisers. The last type of environmental study under pure CO and syngas (i.e. a mixture of H2 :CO = 2:1) revealed the metal particles carburisation at high temperature.

A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study.

BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679.

[Emotion regulation in adolescents with conduct disorder and controls]. / Régulation émotionnelle chez des adolescents présentant des troubles des conduites et chez des témoins.

OBJECTIVES: Although many authors have highlighted similarities between conduct disorder (CD) and alexithymia, little empirical research has actually investigated the contribution of emotion processing to CD. The purpose of this study was to explore the relationships between CD and scores on affect regulation scales among 75 adolescents: a group of 30 adolescents with CD and a group of 45 controls, ranging in age from 13 to 18. METHOD: All participants filled in a socio-demographic questionnaire. CD diagnosis was assessed in regard to DSM-IV criteria using the specific CD section of the Kiddie-Sads. Affect regulation was measured with two self-reports: TAS-20 (Toronto Alexithymia Scale), known as the gold standard for alexithymia measurement, and DERS (Difficulties in Emotion Regulation Scale), a recently validated scale. In addition, since depression may influence the correlations between CD and alexithymia, it was also measured with the BDI. In order to have more information on the CD group, the CTQ was also used. One way analyses of variance adjusting for age were used for mean score comparisons. Partial correlations adjusting for age were used to investigate the link between the CD severity (the severity index was calculated from the Kiddie-Sads) and affect regulation scores. Finally, discriminant analyses were conducted to explore whether affect regulation could correctly categorize controls and adolescents with CD. RESULTS: These results provided some additional data in order to understand the relationship between affect regulation and CD. Controls and adolescents with CD had significantly different emotion regulation scales scores at both scales (TAS-20 and DERS) and in most of their dimensions. Moreover, they also point out the positive correlation between difficulties in affect regulation and CD severity. To our knowledge, this is the first study to have investigated relationships between CD and alexithymia using a severity index of CD. Finally, discriminant analyses showed that the two emotion regulation scales permitted the significant discrimination of both groups. These results are consistent with previous works highlighting the theoretical relationship between deficit in mental elaboration and acting-out. They point to the need to develop therapeutic programs in order to improve emotion regulation of teenagers with CD. Finally, an additional analysis showed a relationship between emotional neglect in childhood (measured with CTQ) and the CD severity. A task for future research would be to study the relationships between attachment, emotional regulation and CD in adolescence.

Patterns of arboreal and terrestrial space use by non-volant small mammals in an Araucaria forest of southern Brazil.

Despite the advances in the techniques for researching arboreal small mammals, detailed ecological data, such as habitat use patterns, are practically nonexistent for many species. Using 150 live-traps installed on the ground, understory (1.0-5.0m) and canopy (>5.0m) we investigated patterns of arboreal and terrestrial space use by small mammals in an Araucaria Forest in southern Brazil (29°29'08″S; 50°12'26″W). We also measured 19 microhabitat variables that could potentially influence the abundance of such mammals on each trap station. The results indicated that Akodon montensis and A. serrensis were mainly terrestrial. Delomys dorsalis was also terrestrial, but it also used understory (17.24% of captures). Juliomys sp. and Gracilinanus microtarsus were the most arboreal small mammals recorded. A. montensis was associated with dense vegetation, while A. serrensis selected positively opened areas. Juliomys sp. and G. microtarsus were associated to microhabitat variables related to the access and movement within the canopy. Moreover, bromeliads on arboreal layer were an important factor for these two arboreal species. This is the first study to report microhabitat associations by Juliomys sp. and A. serrensis, and we demonstrated that vertical stratification and microhabitat use were both synergic mechanisms to determine habitat use by small mammals on the Araucaria Forest of southern Brazil.

[Vaccination post hematopoietic stem cell transplantation: which vaccines and when and, how to vaccinate? An SFGM-TC report]. / Vaccinations post-allogreffe de cellules souches hématopoïétiques: lesquels? Quand? Comment?

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding vaccination post Hematopoietic Stem Cell Transplantation with practical focus on which vaccines to use and when and how to vaccinate?

Acute myeloid leukemia after infliximab: a case report.

Concern has arisen regarding a possible increase in the risk of malignant diseases such as lymphoproliferative disorders in a patient taking TNF-alpha antagonists for the treatment of chronic inflammatory diseases. The evidence of a causal link remains unclear. We report a case of 60-year-old male patient who developed acute myeloid leukemia during infliximab therapy for ankylo-sing spondylitis.

Recent improvement in outcome of unrelated donor transplantation for aplastic anemia.

The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 32+/-8% before 1998 to 57+/-8% after 1998 (P<0.0001). When comparing the cohort before (n=149) and after 1998 (n=349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, P<0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P=0.02) and less chronic GvHD (22 vs 38%, P=0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.

Phase I dose-escalation study of a novel antitumor agent, SR271425, administered intravenously in split doses (d1-d2-d3) in patients with refractory solid tumors.

BACKGROUND: SR271425 is a novel DNA-binding cytotoxic agent with a broad spectrum of antitumor activity in preclinical models,across a variety of the schedule of administration. In toxicological studies, it has been reported to prolong QTc proportionally to C (max). In order to circumvent this C (max)-related QTc prolongation, 5 phase I studies were initiated to investigate 1-h, 24-h, weekly, and split iv infusions. This phase I study assessed a split-dose regimen (a 1-h infusion on each of Days 1 to 3, repeated every 3 weeks) to establish the dose limiting toxicities (DLT), to recommended a phase II dose, and to characterize PK/PD. METHODS: Patient with advanced solid tumors, adequate bone marrow, hepatic, renal function and on specific cardiac criteria were eligible and "3 + 3" design was used for dose escalation. That dose escalation was guided by PK data, toxicities observed and information from other ongoing phase I studies with SR271425. SR271425 plasma levels (PK samples) were measured using a validated LC-MS/MS method. Careful monitoring of ECGs was done, and ECGs were read centrally. RESULTS: Three centers enrolled 19 heavily pretreated patients to six dose levels, from 75 to 450 mg/m(2)/day (i.e., 225-1,350 mg/m(2)/cycle): 12 males and 7 females. Median age 56. Median ECOG, PS = 1. Main tumor types were brain, breast, gynecological, and urological. Patients received a median of 2 cycles (range: 1-6). NCI-CTC Grade 1-2 toxicities included nausea, vomiting, asthenia, rash, and yellow skin discoloration. No DLTs were reported, and there were no dose-limiting prolongations of QTc. Both C (end) and AUC increased in a dose-related manner, with no evidence of accumulation between Day 1 and Day 3, consistent with the mean (+/-SD) terminal elimination half-life of 5.11 +/- 1.21 h. Stable disease was observed in five cases. CONCLUSION: Split doses allow high cumulative exposure to SR271425 without significant toxicity, especially without QTc prolongation. MTD was not reached due to the early termination of the SR271425 program by the sponsor.

A truncated herpes simplex virus thymidine kinase phosphorylates thymidine and nucleoside analogs and does not cause sterility in transgenic mice.

Dividing eukaryotic cells expressing the herpes simplex virus type 1 thymidine kinase (TK) gene are sensitive to the cytotoxic effect of nucleoside analogs such as acyclovir or ganciclovir (GCV). Transgenic mice with cell-targeted expression of this conditional toxin have been used to create animals with temporally controlled cell-specific ablation. In these animal models, which allow the study of the physiological importance of a cell type, males are sterile. In this study, we showed that this phenomenon is due to testis-specific high-level expression of short TK transcripts initiated mainly upstream of the second internal ATG of the TK gene. This expression is DNA methylation independent. To obtain a suicide gene that does not cause male infertility, we generated and analyzed the properties of a truncated TK (delta TK) lacking the sequences upstream of the second ATG. We showed that when expressed at sufficient levels, the functional properties of delta TK are similar to those of TK in terms of thymidine or GCV phosphorylation. This translated into a similar GCV-dependent toxicity for delta TK- or TK-expressing cells, both in vitro and in transgenic mice. However, delta TK behaved differently from TK in two ways. First, it did not cause sterility in delta TK transgenic males. Second, low-level delta TK RNA expression did not confer sensitivity to GCV. The uses of delta TK in cell-specific ablation in transgenic mice and in gene therapy are discussed.

High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia.

Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.

[ABO incompatibility and non myeloablative allogeneic stem cell transplantation]. / Incompatibilité ABO et greffe allogénique de cellules souches hématopoïétiques à l'ère des conditionnements non myéloablatifs.

ABO incompatibility is not a barrier for allogeneic hematopoietic stem cell transplantation but is associated with specific complications. Major ABO incompatibility is associated with delayed erythroid engraftment, increased transfusion requirement and cases of pure red cell aplasia. Minor ABO incompatibility may be responsible for acute haemolytic reactions in the first months following transplantation. The widely used non myeloablative conditioning regimens might modify the management of ABO incompatibility. They could favour pure red cell aplasia development in the setting of major ABO mismatch since they are associated with a prolonged persistence of host anti-donor isohemagglutinins after allogeneic hematopoietic stem cell transplantation. In the setting of minor ABO incompatibility, the use of peripheral blood stem cells and the nature of graft-versus-host disease prophylaxis regimen may have an impact on the incidence of haemolytic reactions. In that review, the clinical and therapeutic aspects of ABO incompatibility are studied, especially regarding the impact of the conditioning regimen intensity.

[Early pneumonia after allogenic stem cell transplantation]. / Complications pulmonaires précoces des allogreffes de cellules souches hématopoïétiques.

INTRODUCTION: Pneumonia is one of the main causes of mortality following allogenic stem cell transplantation, especially in the first months after the transplant has been performed. STATE OF THE ART: Pneumonia is the most common infection occurring after transplant and the infection with the highest mortality. Following the classical, myeloablative approach to transplant, two thirds of the pneumonias that occur are of infectious origin. Their causes roughly follow the timing of the immune reconstitution, and may depend on the type of transplant, the match between donor and recipient, and, overall, the occurrence of graft-versus-host disease. Most bacterial pneumonias occur during the initial neutropenic phase. The 2nd and 3rd month post transplant are mainly complicated by viral pneumonia, especially respiratory virus and adenovirus pneumonia in deeply immunosuppressed patients. Preemptive and prophylactic strategies have considerably reduced the incidence of cytomegalovirus pneumonia. Pneumonia due to encapsulated bacteria, such as Haemophilus influenzae and Streptococcus pneumoniae, usually considered to be late infections, may actually be observed from the second month post-transplant. PERSPECTIVES: The increasing use of reduced-intensity conditioning regimens has modified the time course of the main adverse events following transplantation, including the timing of the infectious pneumonias. The pneumonias that are specifically related to allogenic transplant are idiopathic interstitial pneumonia, bronchiolitis obliterans, and bronchiolitis obliterans organizing pneumonia, which are all considered to be pulmonary manifestations of graft-versus-host disease, and treated as such. Prophylaxis for many of these infectious pneumonias (i.e., P jiroveci, S pneumoniae, toxoplasmosis) are well standardized. CONCLUSIONS: Much remains to be done to decrease the incidence of pneumonia in these patients and to understand their mechanisms.

Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68-48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04-16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17-0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease.