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The aim of this cross-sectional study was to compare women who are not experiencing infertility, women who have experienced infertility in the past, and women who are currently experiencing infertility on illness representations of infertility. Participants were 668 women recruited via social media discussion forums and divided into three groups: not experiencing infertility ( n  = 299), experienced infertility in the past ( n  = 229), and currently experiencing infertility ( n  = 140). Their illness representations (cognitive and emotional) of infertility were measured with the Brief Illness Perception Questionnaire. Comparisons between the three groups showed that women who had not experienced infertility perceived fewer symptoms to be associated with infertility than the other two groups did and attributed infertility more to biological and psychological causes. Women who were currently experiencing infertility reported less negative emotions than the other two groups and attributed their infertility more to contraception, the medical profession, and their weight. Finally, women who experienced infertility in the past perceived more consequences of infertility, considered it to be more long-lasting and attributed it more to substances and environmental causes than the two other groups. Results revealed several differences between the illness representations of infertility in women. These findings highlight the need for information campaigns about infertility, with messages that are more closely tailored to the target population.

Purpose: The prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism., Method: In this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents)., Results: The results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents., Conclusion: The results confirm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly self-directed socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Trait anxiety, emotion regulation strategies, and metacognitive beliefs influence executive functions (EFs) and academic achievement. This study examines their interplay and impact on academic success. In total, 275 adolescents (10-17 years) and parents completed an online questionnaire assessing trait anxiety, emotion regulation strategies, metacognition, parent-reported behaviors related to executive functioning, and overall school average. Preliminary analyses confirmed consistency with the existing literature for each variable and their interaction. Furthermore, we conducted a network analysis among the main variables. This analysis supports the need to pay more attention to reflective variables-maladaptive emotion regulation strategies and metacognitive beliefs about worry-when studying trait anxiety. These variables were linked to problematic executive functioning in adolescents, and the latter was negatively linked to academic achievement. This study offers innovative insights by investigating relationships less explored in the scientific literature. It reveals high and significant correlations between metacognitive beliefs, maladaptive emotion regulation strategies, and trait anxiety (r > 0.500, p < 0.001) but also between these variables and both executive functioning and academic achievement. These findings offer new perspectives for research and underscore the importance of holistically examining the psychological factors related to academic success.

Introduction: The specific cutaneous toxicity of Bruton's tyrosine kinase inhibitors is poorly described. We report a case of severe systemic vasculitis induced by ibrutinib., Observation: A 73-year-old woman with chronic lymphocytic leukemia was treated with ibrutinib. Eighteen months after treatment onset, ulceronecrotic lesions on toes and tongue occurred. Skin biopsy found vasculitis of small and medium vessels. Biologic tests were negative. This vasculitis was refractory to systemic corticosteroid therapy and azathioprine. Ibrutinib was stopped on the hypothesis of drug-induced vasculitis. Skin lesions improved after discontinuation of ibrutinib., Conclusion: The mechanism of action of ibrutinib does not explain the occurrence of vasculitis and an immunoallergic mechanism is suspected., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: the mental health of students was particularly affected by the COVID-19 pandemic. The present study therefore examined the relationships between anxiety and depressive symptoms, eating-related problems, coping, fear of COVID-19, and intolerance of uncertainty., Methods: 2139 French students of 54 universities were recruited in the different regions of France during a French lockdown (between 21 April and 3 May 2021). Six variables were measured: fear of COVID-19, intolerance of uncertainty, coping, anxiety and depressive symptoms, and eating-related problems. To explore the directions of the relationships between our variables of interest, we calculated a directed acyclic graph., Results: our data highlighted the central roles of intolerance of uncertainty in students' anxiety and depressive symptoms, and the direct role of prospective intolerance of uncertainty on eating-related problems., Conclusions: these findings indicate that intolerance of uncertainty should be targeted by interventions designed to help students with high levels of anxiety, depressive symptoms, and/or eating-related problems.

Background: This systematic review and meta-analysis was based on the Common Sense Model, applied to infertility., Aims: The aim was to examine the relationships between cognitive (i.e. cause, coherence, consequences, controllability, identity and timeline) or emotional representations of infertility and both coping (i.e. maladaptive and adaptive) and psychosocial outcomes (i.e. distress, anxiety, depressive symptoms, social isolation, low well-being and poor quality of life), reporting followed PRISMA guidelines., Materials & Methods: Five databases (PubMed, PsycINFO, PsycARTICLES, PubPsych and CINAHL) were searched, and 807 articles were initially identified., Results: Seven cross-sectional studies (N = 1208 participants) were retained in qualitative and quantitative analyses. These studies assessed the associations of seven types of representations with either maladaptive or adaptive coping (20 effect sizes), or with psychosocial outcomes (131 effect sizes). A multivariate meta-analysis revealed that none (0/2) of the associations between the sole type of representation considered (i.e. controllability) and coping strategies were statistically significant, whereas three (3/7) of the associations between representations of infertility and psychosocial outcomes were statistically significant. Regardless of p-values, pooled estimates ranged from low (r = .03) to very high (r = .59)., Discussion: Future studies should validate specific measurement tools for measuring cognitive and emotional representations of infertility., Conclusion: Our results highlight the influence of representations of infertility (particularly cognitive representations of consequences and emotional representations) on the psychosocial outcomes of infertility., (© 2023 British Psychological Society.)

Parental burnout (PB) is a chronic stress-related condition resulting from long-lasting exposure to overwhelming parenting stress. Previous studies showing the seriousness of this condition stressed the urgent need to provide researchers and practitioners with effective assessment tools. Validated PB measures are the Parental Burnout Inventory (PBI) and the Parental Burnout Assessment (PBA). The good psychometric properties of these instruments have been replicated across different samples and countries, but thresholds for identifying impairing PB levels (i.e., cutoff scores) have not yet been established. The present study aims to fill this gap by adopting a multi-informant and multimethod approach to a sample of 192 burned-out and control parents. PBI and PBA cutoffs were derived from the combination of several PB indicators, based on a preregistered analysis strategy. Results identified a score of 74.6 (95% confidence interval (CI) = [69.48-79.68]) for the PBI and 86.3 (95% CI = [79.49-93.03]) for the PBA as indicators of the most severe PB levels.

We argue that: (1) disappointment in the effectiveness of i-frame interventions depends on realistic expectations about how they could work; (2) opportunities for system reform are rare, and i-frame interventions can lay important groundwork; (3) Chater & Loewenstein's evidence that i-frame interventions detract from s-frame approaches is limited; and (4) nonetheless, behavioural scientists should consider what more they can contribute to systemic reforms.

University students are a vulnerable population, and many recent studies show that anxiety, depressive symptoms, and academic burnout have been on the increase since the beginning of the COVID-19 pandemic. These findings point to a need for interventions to reduce these difficulties. The purpose of the present study was to assess the effects of 2 formats of an innovative program on students' mental health (anxiety, depressive symptoms, and academic burnout), intolerance of uncertainty, learned helplessness, and learning. Our sample was composed of 105 university students, recruited on a voluntary basis. They were divided into 3 groups: online intervention group (n = 36), face-to-face intervention group (n = 32), and control group (n = 37). The following variables were measured through online questionnaires: anxiety and depressive symptoms, academic burnout, intolerance of uncertainty, learned helplessness, perceived social support, learning strategies, and beliefs. There were 2 assessments 10 weeks apart (ie, before and after the program in the case of the 2 intervention groups). We performed nonparametric analyses to run comparisons between the 2 assessment timepoints in each group. Results showed that participants in the 2 intervention groups had lower levels of learned helplessness and intolerance of uncertainty at the end of the program. Furthermore, participants in the face-to-face group reported higher levels of perceived social support, academic self-efficacy, and help-seeking strategies. The present study highlighted the benefits of our innovative program, especially its face-to-face format. Clinical Trial - ID: NCT04978194.

Background: In metastatic colorectal cancer (CRCm), fatigue is pervasive, reduces quality of life, and is negatively associated with survival. Its course is explained in part by psychosocial variables such as emotional distress, coping strategies, or perceived control. Thus, to reduce fatigue, psychosocial interventions appear to be relevant. In some cancers, Cognitive Behavioral Therapies (CBT) reduce fatigue. Hypnosis is also used as a complementary therapy to reduce the side effects of cancer. While CBT requires specific training often reserved for psychologists, hypnosis has the advantage of being increasingly practiced by caregivers and is therefore less expensive (Montgomery et al., 2007). On the other hand, CBT and hypnosis remain understudied in the CRC, do not focus on the symptom of fatigue and in Europe such programs have never been evaluated., Objectives: Implementing an intervention in a healthcare setting is complex (e.g., economic and practical aspects) and recruiting participants can be challenging. The primary objective will therefore be to study the feasibility of two standardized interventions (hypnosis and CBT) that aim to reduce fatigue in patients with CRCm treated in a French cancer center., Methods and Design: A prospective, single-center, randomized interventional feasibility study, using mixed methods (both quantitative and qualitative). A total of 60 patients will be allocated to each intervention group [Hypnosis ( n = 30) and CBT ( n = 30)]. Participants will be randomized into two parallel groups (ratio 1:1). Both programs will consist of 6 weekly sessions focusing on the CRF management over a period of 6 weeks. Trained therapists will conduct the program combining 3 face-to-face sessions and 3 online sessions. The feasibility and experience of interventions will be evaluated by the outcome variables, including the adhesion rate, the reasons for acceptability, relevance or non-adherence, the satisfaction, the fatigue evolution (with ecological momentary assessments), and the quality of life. All questionnaires will be self-assessment using an online application from the cancer center., Discussion: Results will highlight the barriers/facilitators to the implementation of the program and the relevance of the program to the patients, and will be used to generate hypotheses for a randomized control trial., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04999306; https://clinicaltrials.gov/ct2/show/NCT04999306., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baussard, Cousson-Gélie, Jarlier, Charbonnier, Le Vigouroux, Montalescot, Janiszewski, Fourchon, Coutant, Guerdoux and Portales.)

While it is now clear that the COVID-19 pandemic has had a major impact on the mental health of individuals, especially the most vulnerable ones such as students, we have very little knowledge about the long-term consequences. The objective of this study was to compare the mental health and coping of French university students during the different phases of the pandemic in the first 2 years. To this end, French university students were evaluated at four time points: during France's first lockdown (April-May 2020; n T1 = 1357), the period after lockdown (June 2020; n T2 = 309), 1 year after the first lockdown, which was also a lockdown period (April-May 2021; n T1' = 2569); and 1 year after the end of the first unlock (June 2021; n T2' = 1136). Anxiety and depressive symptoms, coping and concerns were measured. In order to compare scores between the lockdown and unlock periods within the same year, paired samples t -tests were performed. To compare scores between the 2 years for different participants, independent samples t -tests were conducted. Our results showed that maladaptive strategies, concerns and symptoms were higher during lockdown periods, compared with unlock periods. In addition, symptom levels were higher in the second year of the pandemic compared with the first one. These argue that the psychological effects of COVID-19 were exacerbated by lockdowns but also by time. This highlights the need for more attention to be paid to students' mental health.

The COVID-19 pandemic has had a major impact on university students, particulary on their mental health. However, little is yet known about how to prevent and/or reduce this impact. Prior to COVID-19, some studies have shown that online stress management programs were successful enough to improve students' mental health and stress adjustment strategies, suggesting that these interventions should be further developed during the pandemic. Our study explored the effects on mental health of an online program that targeted stress management and learning. A total of 347 university students were initially recruited to take part in a non-randomized controlled study. After dropout, our final sample consisted of 114 participants, divided into two groups: an intervention group (participants who took part in the program) and the control group (participants who did not participate in the program). The variables measured were: anxiety and depressive symptoms, academic burnout, learned helplessness, and coping strategies. Means comparisons between baseline (T0) and an assessment at 8 weeks (T1) revealed reductions in anxiety symptoms and learned helplessness in the intervention group, but not in the control group. Our pilot study reports promising effects of an online program on students' psychological state., Competing Interests: None declared., (© 2022 Published by Elsevier Ltd.)

Parental burnout, postpartum depression and major depression are conditions that share common symptomologies, but are not to be confused with each other. It is therefore important to define each of these disorders before documenting the similarities, differences and the issue of differential diagnosis in each of these conditions., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Alopecia, although long considered an unavoidable consequence of cancer therapy, currently presents a multifaceted challenge. The knowledge of the physiology of the hair and consequently of the pathophysiology of alopecia has led to show that there is not one but several types of alopecia. Transposed to the world of oncology, different types of alopecia and subsequently molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. Thus, in patients with cancer, alopecia can be iatrogenic (chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy, surgery) or directly the consequence of the disease itself (malnutrition, scalp metastases, paraneoplastic syndromes). Knowledge of the incriminated mechanism(s) could thus make it possible to deploy an appropriate care component, whether on the preventive or curative sides or in terms of supportive care. These are particularly essential regarding the psychological repercussions caused by alopecia, with significant consequences on the quality of life of patients and with a potential impact on treatment compliance. On the preventive side, the last few years have seen the advent of the automated scalp cooling therapy, supported by several randomized clinical trials. On the curative side, several therapeutic proposals are currently deployed or under development in order to provide relevant treatments., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Many studies have highlighted the negative mental health consequences of lockdowns. However, to date, we do not know how these consequences change over time. The first objective of the present study was to track changes in adjustment strategies and clinical issues among French university students at different times of the pandemic. The second objective was to investigate the psychological and situational factors contributing to students' anxiety and depressive symptoms., Method: This cohort study was conducted between 23 April and 11 December 2020. Measurements were performed four times: during France's first national lockdown, during the period after lockdown, when universities were open, and finally during the second national lockdown. A total of 1294 university students were initially included, and 91 students completed the four measurement points over a 7-month period. Coping strategies (with the Brief-COPE), health concerns (with two questions), anxiety and depressive symptoms (with the HADS) were measured., Results: Results showed an evolution over time of anxiety (χ 2 = 21.59 ***) and depressive (χ 2 = 29.73 ***) symptoms. Depressive symptoms are significantly higher during lockdown periods compared to unlockdown periods. Anxiety symptoms are likewise particularly high during the two lockdowns, but also when the universities reopen. At different times, anxiety and depressive symptoms were positively associated with maladaptive strategies, such as the self-blame (rho between 0.33 and 0.51) and negatively with adaptive strategies, such as the positive reframing (rho between -0.23 and -0.44)., Conclusions: The trajectory of anxiety, which is elevated even in the absence of lockdown, raises concerns about the long-term effects of the pandemic on these symptoms.

Many studies have highlighted the impact of lockdowns on the lifestyle of university students. We do not, however, know how these lifestyles have changed over the course of the COVID-19 pandemic. The objective of the present study was to describe changes in the levels of physical activity, sedentary behaviors, and alcohol consumption in French university students during different periods of the pandemic. This cohort study was conducted between 23 April and 11 December 2020. Measurements were performed four times: Twice during two successive lockdowns and twice during the intervening period. A total of 1294 university students were initially included, and 91 students completed the four measurement points over a seven-month period. Alcohol consumption, physical activity, and sedentary behaviors were measured. The results revealed high levels of physical activity during the first lockdown, but a subsequent decline during the pandemic that was partly explained by time. The pandemic had a positive effect on alcohol consumption. Sedentary levels were higher during both lockdowns, and sedentary behaviors tended to persist over time. This study raises concerns about the long-term effects of the pandemic on students' health and lifestyle. The preponderance of distance learning should be reconsidered, given the negative impact of physical inactivity and sedentary behavior on long-term health, especially in young adults., Competing Interests: The authors declare no conflict of interest.

Even before the current pandemic, university students were known to have high levels of hassles, anxiety, and depressive symptoms. In all probability, the advent of COVID-19 has substantially raised these levels. The present study measured the emotional state of university students during lockdown and identified the relevant situational and psychological factors. To this end, 1,297 French university students were assessed during lockdown, which lasted from 16 March to 11 May in France. Situational factors included the belief that lockdown was compromising their future job prospects, COVID-19 symptoms, and health concerns. Psychological factors included students' implicit theory of emotion, and the coping strategies they used during lockdown. We explored the extent to which these factors were associated with levels of hassles, anxiety, and depressive symptoms. Results indicated that students' belief that lockdown was compromising their future job prospects was positively related to hassles ( r = .34, p < .001), while concerns about their own health and that of relatives were positively associated with anxiety ( r = .37 and .34; p < .001). In addition, use of the positive reframing coping strategy mediated the effect of students' implicit theory of emotion on their depressive symptoms. Even though the national lockdown is now over, the pandemic will continue to have a major impact on university students over the coming months. It is therefore essential for universities to provide them with adequate psychological support.

Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Next-generation sequencing (NGS) is used to investigate the presence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a reallife setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspected myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow samples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the application of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic mutations had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.

High levels of stress in the parenting domain can lead to parental burnout , a condition that has severe consequences for both parents and children . It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; M age = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-020-00028-4., Competing Interests: Conflict of InterestThe authors declare no competing financial interests or funding source that could have influenced the data collection, analysis, or conclusions. M.M. and I.R. have now founded a training institute (name currently masked for blind review) which delivers training on parental burnout to professionals. The institute did not participate in the funding of this study nor did it influence the process, the results, or their interpretation in any manner., (© The Society for Affective Science 2021.)

Enhancing positive affect (PA) and reducing negative affect (NA) are targets of positive psychology interventions, and well-being and positive functioning are core elements of mental health. However, the underlying temporal dynamics of these elements are unknown. This study aimed at identifying how a 42-day daily positive psychology intervention (PPI) impacts affective longitudinal dynamics compared to a control condition. This study employed an experience sampling method (self-observation diary including the Measurement of Affectivity: Valence/Activation scale, MAVA) with two non-randomised groups-a control group (n = 43) and an intervention group (n = 43)-taken from a community sample. Compared to the control participants, the PPI participants' trajectories for activated and deactivated NA showed an important decrease over the course of the PPI. The deactivated PA trajectory increased non-linearly across the PPI, whereas the activated PA trajectory showed a linear increase. This study suggests that PPIs change daily affective life., (© 2020 International Association of Applied Psychology.)

Thirty patients, with high-risk acute myeloid leukemia (AML, n = 20) or myelodysplastic syndrome (MDS, n = 10), were enrolled in a phase II trial entailing prophylactic post-transplant azacitidine (AZA) plus escalated doses of donor lymphocyte infusion (DLI). The median number of AZA cycles was 5 (1-12) with 10 patients (33%) completing the 12 projected cycles. DLI were performed in 17 patients: 5 received one DLI, 2 received 2 DLI and 8 received 3 infusions. AZA was well tolerated, but discontinued in 20 patients primarily due to graft-versus-host disease (GvHD) and relapse. The cumulative incidence (CI) of grade 1-3 acute GvHD was 31.5% and the chronic GvHD CI was 53% at 2 years. At a median follow-up of 49 months (27-63), 18 patients are alive. The overall and disease-free survivals are 65.5% (CI 95% = 48.2-82.8) at 2 years. Cause of death was mainly relapse for 9 patients. The median time to relapse was 7 months (2.5-58) and the cumulative incidence of relapse at 2 years was 27.6% (CI 95% = 12.8-44.6). These results confirm that AZA is well tolerated as a prophylactic treatment to reduce the risk of post-transplantation relapse and compared favorably to those of patients who receive no post-transplant maintenance.

Purpose: We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT)., Patients and Methods: We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients., Results: Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration., Conclusion: This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

This preliminary study aimed to understand the effects of an autonomous mindfulness-based intervention (MBI) on mindlessness propensities: rumination, automatic pilot functioning, and attentional distractibility. The ecological momentary assessment was completed by community participants assigned to two nonrandomized groups: an experimental group ( n = 45) that practiced 20-minute daily mindfulness meditation for 42 days and a control group ( n = 44) that was on the waiting list for the MBI. All participants completed a self-assessment on rumination and mindlessness propensities twice a day. The MBI led to a favorable gradual decrease in automatic pilot functioning and attentional distractibility. Rumination evolved in three stages: a rapid decrease during the first week, a stabilization phase between the 10th and 30th days, and an additional decrease after 30 days of practice. This innovative study provides a promising perspective regarding rumination, automatic pilot functioning, and attentional distractibility dynamic trajectories over the course of an MBI., (© 2018 Springer Publishing Company, LLC.)

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment. We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed. A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%. In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant., (© 2018 Wiley Periodicals, Inc.)

Background: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation., Methods: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate., Results: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT., Conclusions: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD., (© 2017 The Association for the Publication of the Journal of Internal Medicine.)

Gastrointestinal (GI) graft-versus-host-disease (GVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation, but clinical and histological features are unspecific. The aim of this study was to correlate the histological GI GVHD grade with the clinical outcomes. In a retrospective study of 112 patients with clinically suspected GI GVHD, colonic biopsies were reviewed by three pathologists without knowledge of the corresponding clinical data and classified in four scores, according to the NIH Consensus Project recommendations: no GVHD, possible, probable, and unequivocal GVHD. At the end of the study, the histological and clinical data were confronted with the following results: clinical diagnosis of GI GVHD was established for 70 patients (62.5%) and histological scores correlated well with the clinical diagnosis (p < 0.001) and particularly with the prognosis (p < 0.05).When severe lesions were observed, the 1 year overall survival declined to 9%. None of the features reported in the literature to support GVHD diagnosis, eosinophil count, endocrine cells aggregate, immunohistochemical analysis (cytomegalovirus, CD123, chromogranin), did not help us for diagnosis. So routine histopathology alone without immunohistochemistry is a strong and reproducible tool to diagnose GI GVHD with the help of clinical and biological information, and most importantly, histological grading proved to be a powerful prognostic value.

We examined age-related differences in the reactive and proactive use of affect regulation strategies. We collected data from 209 participants 13-80 years of age, using an experience sampling method. The most interesting finding was that, as hypothesized, compared with those under 20, adults 20 and over used the 2 strategies we focused on (i.e., problem solving and positive reappraisal) more intensely and in a reactive manner. By contrast, from the age of about 55 upward, adults were characterized by a more intensely proactive use of these strategies. Results are discussed in the light of age differences in motivation. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

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.

Background: Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet., Patients and Methods: This was a retrospective with the aim to compare the outcomes of NHL patients who received before allo-SCT a fludarabine/busulfan conditioning regimen, either of reduced intensity (FB2, 2 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 277) or at a myeloablative reduced-toxicity dose (FB3/FB4, 3 or 4 days of busulfan at 4 mg/kg/day oral or 3.2 mg/kg/day i.v.) (n = 101)., Results: In univariate analysis, the 2-year overall survival (FB2 66.5% versus 60.3%, P = 0.33), lymphoma-free survival (FB2 57.9% versus 49.8%, P = 0.26), and non-relapse mortality (FB2 19% versus 21.1%, P = 0.91) were similar between both groups. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) (FB2 11.2% versus 18%, P = 0.08), extensive chronic GVHD (FB2: 17.3% versus 10.7%, P = 0.18) and 2-year GVHD free-relapse free survival (FB2: 44.4% versus 42.8%, P = 0.38) were also comparable. In multivariate analysis there was a trend for a worse outcome using FB3/FB4 regimens (overall survival: HR 1.47, 95% CI: 0.96-2.24, P = 0.08; lymphoma-free survival: HR: 1.43, 95% CI: 0.99-2.06, P = 0.05; relapse incidence: HR 1.54; 95% CI: 0.96-2.48, P = 0.07). These results were confirmed using a propensity score-matching strategy., Conclusion: We conclude that reduced toxicity myeloablative conditioning with fludarabine/busulfan does not improve the outcomes compared with reduced-intensity conditioning in adults receiving allo-SCT for NHL., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study shows the long-term updated outcomes of a multicenter retrospective study which analyzed 843 patients with myelodysplastic syndrome (MDS) who underwent transplantation with an HLA-identical sibling donor with either reduced-intensity conditioning (RIC) in 213 patients, or standard myeloablative conditioning (MAC) in 630 patients. In multivariate analysis, the 13-year relapse rate was significantly increased after RIC (31% after MAC vs 48% in RIC; HR, 1.5; 95% CI, 1.1-1.9; P=0.04), but with no differences in overall survival (OS) (30% after MAC vs 27% in RIC; P=0.4) and PFS (29 vs 21%, respectively, P=0.3). Non-relapse mortality was higher in MAC (40 vs 31%; P=0.1), especially in patients older than 50 years (50 vs 33%, P<0.01). In addition, long-term follow-up confirms the importance of other variables on 13-year OS, mainly MDS risk category, disease phase, cytogenetics and receiving a high donor cell dose, irrespective of the conditioning regimen used.

High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.

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.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB)., Methods: Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment., Results: One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 10 3 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease., Conclusions: Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).

60-70% of AML patients have an indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their treatment. Graft versus host disease (GvHD), the major cause of mortality and comorbidities post-transplantation, develops by immunological mechanism and decides greatly prognosis and quality of life (QoL) of graft recipient. Current GvHD prophylaxis is not personalized. Infections, toxicities and leukemic infiltration complicate the first chemotherapy phases prior to allo-HSCT. They, to certain extent, induce local immune stimulation. Impact of immune stimulation of this period on incidence of GvHD has not been evaluated. We retrospectively studied 238 AML patients transplanted at first remission from 21 French centers in the ALFA-0702 protocol and found that cutaneous and digestive immune stimulation during induction increases the incidence of skin and gut aGVHD, respectively. Furthermore, prolonged febrile duration correlates with elevated incidence of grade II-IV aGvHD. Thus, we identified a group of patients with higher risk of aGvHD. The benefit of personalized GvHD prophylaxis should be explored in a prospective cohort to decrease incidence of aGvHD in these patients and improve their QoLs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24., (© 2017 by The American Society of Hematology.)

Background: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option., Methods: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry., Results: One hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients' age., Conclusions: In contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.

The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m 2 /day) and cytosine arabinoside (1 g/m 2 /day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26-64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174., (Copyright© Ferrata Storti Foundation.)

Background: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach., Methods: We analyzed long-term outcomes in a cohort of 1423 AML patients, age ≥50 years, after SCT from HLA-matched siblings, during the years 1997-2005, median follow-up 8.3 years (0.1-17)., Results: The 10-year leukemia-free survival (LFS) was 31 % (95CI, 27-35) and 32 % (28-35) after MAC and RIC, respectively (P = 0.57). The 10-year GVHD/ relapse-free survival (GRFS), a surrogate for quality of life was 22 % (18-25) and 21 % (18-24), respectively (P = 0.79). The 10-year non-relapse mortality (NRM) was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65-76) and 73 % (67-78) after MAC and RIC, respectively (P = 0.76). Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC., Conclusions: Long-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches.

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., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The idiopathic inflammatory bowel diseases (IBDs) Crohn's disease and ulcerative colitis are associated with increased risk of hematologic malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) could be a curative strategy in this setting, but has been thought to be associated with increased nonrelapse mortality (NRM). We conducted a national French retrospective analysis of patients with IBD who underwent allogeneic HSCT for hematologic malignancies and were matched with 3 controls according to recipient, donor, and transplant characteristics. Between 2004 and 2015, 18 patients with IBD underwent allogeneic HSCT. With a median follow-up of 33 months for the patients with IBD and 57 months for controls, the cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 39% for the patients with IBD and 40% for controls (hazard ratio [HR], 1.10; P = .82). The cumulative incidence of chronic GVHD at 48 months was 52% for the patients with IBD and 43% for controls (HR, 0.92; P = .89). Nonrelapse mortality at 48 months was 19% for the patients with IBD and 11% for controls (HR, 4.93; P = .067). Overall survival at 48 months was 59% for the patients with IBD and 60% for matched controls (HR, 1.35; P = .56). In conclusion, IBD should not be considered a contraindication for transplantation, and its impact on comorbidity indexes should be reduced., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia., (Copyright© Ferrata Storti Foundation.)

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes., Competing Interests: The authors report no potential conflicts of interest.

We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan-cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10(-5) and 10(-4), respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34-0.86), P=0.01) and overall survival (HR=0.54 (0.34-0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.

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.