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Background: The period of community re-entry following residential substance use treatment is associated with elevated risk for return to substance use. Although continuity of care is best practice, many individuals do not engage in follow-up treatment, struggle to engage in follow-up treatment, or continue to use substances while participating in follow-up treatment. There is a need to both characterize treatment engagement during community re-entry following residential substance use treatment as well as understand how treatment impacts substance use during this high-risk period., Method: This observational study used retrospective self-report to examine treatment engagement and substance use among individuals who had exited residential substance use treatment. Participants completed a Timeline Follow-back interview reporting substance use and treatment engagement in the 30 days following residential treatment., Results: Most participants (83.1 %) reported engaging in substance use treatment following discharge. The most common treatments were Alcoholics Anonymous/Narcotics Anonymous (61.1 %), medication for addiction treatment (40 %), and outpatient therapy (29.2 %). Participants were less likely to use substances on a day in which they engaged in outpatient therapy (OR = 0.32, 95 % CI [0.12, 0.90], p = 0.030) and more likely on days they engaged in medication treatment (OR = 21.49, 95 % CI [1.46, 316.74], p = 0.025)., Conclusion: Findings characterize engagement in substance use treatment in the month following residential treatment. Treatment engagement was common during community re-entry; however, only outpatient therapy was found to reduce substance use during this high-risk period. Findings may inform intervention efforts during the high-risk period of community re-entry., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report. This research was supported by a grant from the Rhode Island Foundation awarded to Nicole H. Weiss. Work on this paper by Nicole H. Weiss was also supported by a grant from the Center for Biomedical Research and Excellence (COBRE) on Opioids and Overdose funded by the National Institute on General Medical Sciences (P20GM125507). Work on this paper by Emmanuel D. Thomas was supported by National Institute on Alcohol Abuse and Alcoholism Grant F31AA030502 and by National Institute on Alcohol Abuse and Alcoholism Grant R25AA028464. Work on this paper by Silvi C. Goldstein was supported by National Institute on Alcohol Abuse and Alcoholism Grant F31AA029274. Work on this paper by Lyn Stein was supported by U01DA05044., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Substance use is highly prevalent among women experiencing intimate partner violence (IPV) and has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and resulting cortisol response. Posttraumatic stress disorder (PTSD) symptoms may play an important role in exacerbating the association between cortisol levels and substance use behaviors., Purpose: This study examined the role of PTSD symptoms in the relation between cortisol and past month substance use behaviors. The current study used hair cortisol as an index of past 30-day HPA-axis functioning and ecological momentary assessment (EMA) to characterize substance use behaviors more accurately over a 30-day period., Method: Participants were 90 community women who had experienced physical or sexual IPV in the past 30 days by their current male partner and used any amount of alcohol or drugs (M age = 40.71; 54.4 % white). Participants completed (a) a baseline interview, (b) EMA for 30-days, and (c) a follow up interview where they were asked to provide a hair sample for cortisol analyses. Data collection took place from 2018 to 2020., Results: PTSD severity moderated the relations between cortisol and days of drinking and binge drinking. In the context of high PTSD symptomology, women with high cortisol levels spent, on average, an additional 7.4 days drinking and 8.1 days binge drinking in the past 30 days compared to women with low cortisol levels, in a model adjusted for age., Conclusions: Results highlight the prominent role of PTSD symptoms in the association between cortisol and alcohol use among women experiencing IPV., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024. Published by Elsevier B.V.)

Background: Literature underscores the importance of emotion dysregulation in clinical research. However, one critical limitation of the existing investigations in this area involves the lack of psychometrically valid measures for assessing emotion dysregulation in individuals' daily lives. This study examined the factor structure and psychometric properties of momentary versions of the Difficulties in Emotion Regulation Scale (mDERS) and the Difficulties in Emotion Regulation Scale-Positive (mDERS-P)., Methods: Participants were 145 community women ( M age = 40.66, 40.7% white) experiencing intimate partner violence and using substances who participated in a baseline interview and then completed surveys three times a day for 30 days., Results: Analyses supported the reliability of the mDERS and the mDERS-P. The two-state, two-trait model, with separate factors for negative and positive emotion dysregulation at both the within-and between-levels, fit the data best. Momentary negative, but not positive, emotions were positively related to the mDERS; both momentary negative and positive emotions were positively related to the mDERS-P. Baseline trait negative, but not positive, emotion dysregulation, was related to greater variability in momentary negative and positive emotion dysregulation., Conclusion: Findings advance our understanding and measurement of emotion dysregulation using intensive longitudinal approaches.

Background: Minoritized racial/ethnic and sex assigned at birth/gender groups experience disproportionate substance-related harm. Focusing on reducing substance-related harm without requiring abstinence is a promising approach. Objectives: The purpose of this meta-epidemiologic systematic review was to examine inclusion of racial/ethnic and sex assigned at birth/gender in published studies of nonabstinence-inclusive interventions for substance use. Methods: We systematically searched databases (PubMed and PsycINFO) on May 26, 2022 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Articles were eligible for inclusion if they: 1) reported in English language, 2) had a primary goal of investigating a nonabstinence-inclusive intervention to address substance use, 3) used human subjects, and 4) only included adults aged 18 or older. Two coders screened initial articles and assessed eligibility criteria of full text articles. A third consensus rater reviewed all coding discrepancies. For the remaining full-length articles, an independent rater extracted information relevant to study goals Results: The search strategy yielded 5,759 records. 235 included articles remained. Only 73 articles (31.1%) fully reported on both racial/ethnic and sex assigned at birth/gender, and only seven articles (3.0%) reported subgroup analyses examining treatment efficacy across minoritized groups. Nine articles (3.8%) mentioned inclusion and diversity regarding both racial/ethnic and sex assigned at birth/gender in their discussion and four articles (1.7%) broadly mentioned a lack of diversity in their limitations Conclusion: Findings highlight that little is known about nonabstinence-inclusive interventions to address substance use for individuals from minoritized racial/ethnic and sex assigned at birth/gender groups.

Objective: Women of Color (WoC) experiencing intimate partner violence (IPV) have elevated rates of posttraumatic stress disorder (PTSD) and alcohol use and related harm (e.g., increased alcohol use and negative consequences). This secondary data analysis assessed the role of racial microaggressions in the association between PTSD and alcohol use and related harm among WoC experiencing IPV. Methods: Participants were 103 WoC currently experiencing IPV and using substances ( M age =40.39, 51.5% Black) who were recruited from the community and completed assessments of PTSD, racial microaggressions, and alcohol use and related harm. Results: Assumptions of Inferiority (e.g., intelligence; B  = 1.44, SE  = 0.90, 95% CI [0.10, 3.54]) and Environmental Microaggressions (e.g., portrayal in media; B  = 1.88, SE  = 1.03, 95% CI [0.28, 4.30]) explained the association between PTSD and alcohol use and related harm. Conclusions: Findings underscore the influence of specific microaggressions in the relation between PTSD and alcohol use and related harm among WoC experiencing IPV.

Background: Emotional suppression is a clinically significant aspect of emotion regulation with robust associations to psychopathology, including posttraumatic stress disorder (PTSD). Despite the fast-growing body of literature highlighting the role of positive emotion regulation difficulties in the development and maintenance of PTSD, extant work on emotional suppression and PTSD has almost exclusively focused on the role of negative emotions., Objective: The present study aimed to advance this literature by examining the associations between PTSD symptom clusters and participants' use of state emotional suppression during a laboratory task designed to elicit negative or positive emotions., Method: Participants were 108 community women ( M age = 39.55; 33% Black/African American) currently experiencing intimate partner violence (IPV) by a male partner and using substances. Participants were interviewed using a structured diagnostic assessment for PTSD and reported on state emotional intensity and emotional suppression following idiographic negative or positive emotion inductions., Results: Results of the moderation analyses showed that, when controlling for state emotional intensity, women experiencing clinical levels of PTSD symptom Clusters B (intrusive recollections), D (negative alterations in cognitions and mood), and E (alterations in arousal and reactivity) were significantly more likely to utilize emotional suppression, but only in the context of positive-not negative-emotions., Conclusions: Findings provide evidence for a link between PTSD and positive emotional suppression among women currently experiencing IPV by a male partner and using substances, highlighting positive emotional suppression as a potential target in PTSD treatment for IPV populations with comorbid substance use concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Substance use has been identified by Indigenous populations as contributing to health disparities facing their communities. Rates of trauma exposure and post-traumatic stress disorder are higher in Indigenous, compared to non-Indigenous, populations and have been linked to substance use. Historical trauma is thought to be one mechanism underlying substance use and related disorders. The purpose of the present study is to summarize the current state of the literature focusing on the association between trauma (historical and lived) and substance use among Indigenous populations in the United States and Canada. Databases were systematically searched using the preferred reporting items for systematic reviews and meta-analyses statement. The search strategy initially yielded 4,026 articles. After exclusion of ineligible articles, 63 articles remained for synthesis. Results of the present review provide evidence for a positive link between substance use and both historical trauma (i.e., 86.4% of studies) and lived trauma (i.e., 84.7% of studies). Indigenous participants reported that historical trauma and pain related to loss of cultural identity contributed to substance use in their communities. Indigenous participants also consistently described an association between lived trauma and substance use. Despite heterogeneity among Indigenous communities, findings suggest a significant association between trauma and substance use across many different tribes and settings (e.g., reservation/reserve, rural/urban). Indigenous participants identified healing from trauma and reconnecting with culture as necessary components for reducing substance use and maintaining sobriety. With this, the development and implementation of interventions should partner with Indigenous communities in a manner that promotes and enhances cultural values for healing., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: First Nations peoples experience disproportionate health inequities compared to most non-Indigenous populations. Historical trauma is one factor that has received growing attention in relation to health inequities among First Nations populations. The goal of the present study was to improve understanding of the specific forms, impacts, and mechanisms of transmission of events that lead to historical trauma and the historical trauma response in First Nations peoples., Method: Five focus groups were conducted among adult members of one First Nations community in Canada ( N = 34; 70.4% female)., Results: Conventional content analysis revealed the numerous forms that historical trauma take in this First Nations community; individual-, familial-, community-, and societal-level impacts of historical trauma; and ways in which historical trauma has been transmitted in this community. Loss of culture, alcohol use, and parenting were major themes identified across these domains., Conclusions: Findings provide important information on the experience of historical trauma in one First Nations community, highlighting the roles of loss of culture; alcohol use; and parenting in the forms, impacts, and transmission of historical trauma. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: Amazon's Mechanical Turk (MTurk) appears to be a reliable resource for studying clinical populations and accessing hard-to-reach populations. Recent research suggests that MTurk may also be a viable option for military recruitment., Objective: The goal of the current study was to examine the utility of collecting clinical data on military samples recruited via MTurk., Method: Participants were 535 military veterans ( M age = 37.45; 71.8% men; 69.5% White) who completed measures assessing trauma and mental health., Results: Findings indicate that rates of military traumas and mental health diagnoses were higher than published comparisons; posttraumatic stress disorder (PTSD) and depression symptoms were found to be higher than values found in a nationally representative sample, lower than a treatment-seeking sample, and comparable to a MTurk-recruited military sample. Alcohol misuse was found to be higher than both nationally representative and treatment-seeking samples. Psychometric analyses indicated support for convergent validity of measures, and confirmatory factor analysis results demonstrated that empirically supported factor models of PTSD were replicated in the current sample; the hybrid model demonstrated the best fit., Conclusions: Our findings support the utility of MTurk for collecting clinical data on military samples. Increasing access to and recruitment of military samples is important for advancing the field of military psychology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Women experiencing intimate partner violence (IPV) are at increased risk for developing hazardous patterns of cannabis use. Research suggests that women experiencing IPV use cannabis to cope with posttraumatic stress disorder (PTSD) symptoms. To advance research, we used experience sampling methods to explicate the within-day concurrent and proximal relations between PTSD symptom clusters and cannabis use among women experiencing IPV., Method: Participants were 145 community women (M age = 40.66, 41.6% white, 31.4% Black, 10.9% Hispanic or Latina, 8% American Indian/Alaska Native, 5.8% Bi-/multi-racial) experiencing IPV and using substances who completed three surveys a day for 30 days., Results: Externalizing behavior (OR = 1.37, 95% CI [1.15, 1.65], p < 0.001) and dysphoric arousal (OR = 1.27, 95% CI [1.09, 1.49], p = 0.002) PTSD symptom clusters were associated with cannabis use reported in the same survey period. Results from the lagged models found no proximal associations between PTSD symptom clusters and cannabis use., Conclusions: Results highlight the acute effects of externalizing behavior and dysphoric arousal PTSD symptoms on cannabis use among women experiencing IPV. These findings may inform prevention and intervention efforts for cannabis use in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

American Indian (AI) adolescents experience disproportionate alcohol-related consequences. The present study evaluated the psychometric properties and application of the American Drug and Alcohol Survey (ADAS™) alcohol-related consequence scale for AI adolescents through a secondary analysis of a large population-based sample of adolescents living on or near AI reservations. We found support for the ADAS alcohol-related consequence scale as a one-factor model, invariant discretely across race, sex assigned at birth, and age, and with good internal consistency. Evidence for construct validity was found through significant positive correlations between frequency of past 12 months of drinking, frequency of past 12 months of intoxication, and lifetime alcohol-related consequences. AI adolescents were significantly more likely to report more alcohol-related consequences than their non-Hispanic White peers. Race significantly interacted with frequency of drinking in predicting alcohol-related consequences such that these associations were stronger for AI adolescents. However, race did not significantly interact with frequency of intoxication in predicting alcohol-related consequences. Results from this study demonstrate the utility of the ADAS alcohol-related consequence scale for use across demographic groups with little risk of measurement bias.

Objective: People experiencing homelessness are disproportionately impacted by alcohol-related harm. Racially minoritized groups are disproportionately represented in the homeless population and are likewise disproportionately impacted by alcohol-related harm. Most alcohol outcome measures have not been adequately psychometrically studied in this marginalized population and across racial groups. This study documents psychometric properties, including measurement invariance, reliability, and convergent validity, of a measure of alcohol-related harm, the Short Inventory of Problems (SIP-2R), across Black, North American Indigenous (NAI), and White adults experiencing homelessness and alcohol use disorder (AUD)., Method: Adults experiencing homelessness and AUD who had participated in one of two randomized controlled trials of harm-reduction treatment ( N = 493; NAI = 205, Black = 125, and White = 163) were included in this psychometric study of the 15-item SIP-2R., Results: Multigroup confirmatory factor analysis (MGCFA) indicated that a model comprising one general alcohol-related harm factor overarching five factors, showed close fit and partial scalar invariance, χ ²(329, N = 493) = 624.902, p < .001, comparative fit index (CFI) = .966, root-mean-square error of approximation (RMSEA) = .074, 90% CI [.066, .083], standardized root-mean-square residual (SRMR) = .063, confirming acceptable measurement equivalence across racial groups. The SIP-2R showed internal consistency (α = .94, ω = .95) and convergent validity, that is, positive correlation between the total SIP-2R score and the number of drinks consumed the heaviest drinking day, ρ(490) = .30, p < .001., Conclusion: This study provided support for the internal consistency, convergent validity, and cross-group measurement equivalence of the SIP-2R for NAI, Black, and White adults experiencing homelessness with AUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Women experiencing intimate partner violence (IPV) experience a heightened prevalence of alcohol use disorder (AUD). Hypothalamic-pituitary-adrenal (HPA)-axis functioning has been associated with increased risk for AUD in other populations, including individuals with posttraumatic stress disorder (PTSD) symptoms. The goal of the present study was to determine whether PTSD symptom severity exacerbates the relationship between HPA-axis functioning and AUD. Participants were 151 community women who had experienced physical or sexual IPV in the past 30 days by their current male partners and used any amount of alcohol or drugs. A two-phase emotion induction protocol was utilized: Neutral mood induction followed by randomly assigned negative, positive, or neutral emotion induction. Saliva cortisol samples were obtained immediately following the neutral mood induction (baseline HPA-axis functioning), 20 min following the individualized emotion induction script (HPA-axis reactivity), and 40 min post the emotionally evocative cue (HPA-axis recovery). Findings revealed that PTSD symptom severity moderated the relations between baseline HPA-axis functioning and HPA-axis recovery and log odds of meeting criteria for AUD. Specifically, baseline HPA-axis functioning was positively associated with log odds of meeting criteria for AUD at high (but not low) PTSD symptom severity, whereas HPA-axis recovery was negatively associated with log odds of meeting criteria for AUD at high (but not low) PTSD symptom severity. Results contribute to our understanding of the biological processes involved in the etiology and maintenance of AUD among women experiencing IPV-specifically the prominent role of PTSD symptom severity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Adolescent alcohol use is a significant public health concern and rates of alcohol use are higher among American Indian (AI) adolescents than national samples of non-AI youth. A potential factor in understanding AI alcohol use is cultural identity, which can vary widely based on experiences of historical trauma. We used latent class analysis to examine cultural identity in AI and White adolescents and their alcohol use outcomes in relation to the latent class solutions., Methods: The samples included 3189 AI adolescents (M age  = 14.76, 48.9% female) and 1579 White adolescents (M age  = 15.56, 48.7% female) living on or near a reservation. Participants completed self-report measures of AI and White cultural identity affiliation, alcohol use, and alcohol-related problems. We examined (1) the best-fitting latent class solution with respect to American Indian (AI) and White cultural identity; (2) equivalence of the latent class solution; and (3) alcohol use outcomes across the optimal latent class solution., Results: Latent profile analyses indicated an optimal 3-class solution in both the AI and White samples, which differed by level of affiliation with AI and White cultural identity. While the optimal number of classes were similar across racial groups (configural profile similarity), the nature of the classes differed (structural profile dissimilarity). The three classes represented low overall scores on AI and White cultural identity (Marginalized), a mixture of high and low scores on AI and White cultural identity (Third Culture), and overall high scores on AI and White cultural identity (Bicultural). Alcohol-related problems predicted membership in the Third Culture class compared with the Marginalized class and the Bicultural class. Specifically, youth in the Third Culture class reported significantly fewer alcohol-related problems than youth in the Marginalized and Bicultural classes. Alcohol use did not predict latent class membership., Conclusions: The future-oriented nature of the Third Culture class may provide protection against adverse alcohol-related outcomes. Research is needed to test interventions that target greater future orientation and future plans to integrate culture into adolescents' lives., (© 2022 Research Society on Alcoholism.)

Aims: The present study assessed community and culturally specific alcohol-related harm among North American Indigenous (NAI) individuals, as well as the acceptability and feasibility of harm reduction approaches in one reserve-based NAI community., Methods: Participants lived on or near a NAI reserve in Canada. Semi-structured focus groups were conducted with health care workers (N = 8, 75% NAI) and community members (N = 9, 100% NAI). Self-report questionnaires were administered that measured acceptability and feasibility of harm reduction strategies., Results: Conventional content analysis revealed loss of culture as culturally specific alcohol-related harm. Health care workers rated harm reduction approaches to be acceptable and feasible, while community participants were more mixed. Majority of participants felt that some harm reduction strategies could provide opportunities for individuals who use alcohol to connect to Indigenous culture and traditions. However, there were mixed findings on whether harm reduction strategies are consistent with Indigenous cultural traditions and values., Conclusion: Future research is needed to evaluate potential utility of harm-reduction approaches for NAI communities., (© 2022 Wiley Periodicals LLC.)

Background: Research examining emotion dysregulation and alcohol use has increased exponentially over the past decade. However, these studies have been limited by their use of cross-sectional designs and narrow definitions of emotion dysregulation. To address these significant gaps in the extant literature, this study utilized state-of-the-art methodology (i.e., experience sampling) and statistics (i.e., dynamic structural equation modeling) to examine potential reciprocal associations between negative and positive emotion dysregulation and alcohol use at the momentary level., Methods: Participants were 145 community women (mean age = 40.56, 40.3% white) experiencing intimate partner violence (IPV) and using substances. Surveys assessing negative and positive emotion dysregulation and alcohol use (i.e., number of standard drinks) were administered three times a day for 30 days using phone-based interactive voice recording., Results: Significant contemporaneous effects indicated that negative and positive emotion dysregulation both co-occurred with alcohol use. However, levels of negative and positive emotion dysregulation did not predict later alcohol use, nor did alcohol use predict later levels of negative or positive emotion dysregulation. There was significant variability among participants in cross-lagged effects., Conclusions: Findings showed that negative and positive emotion dysregulation co-occurred with alcohol use and that there was significant interindividual variability in the cross-lagged associations between negative and positive emotion dysregulation and alcohol use. Research using idiographic approaches may identify women experiencing IPV for whom negative and positive emotion dysregulation drive alcohol use and alcohol use drives negative and positive emotion dysregulation., (© 2022 Research Society on Alcoholism.)

Background: American Indian (AI) adolescents report disproportionate higher rates of alcohol use and alcohol-related consequences than adolescents from other racial/ethnic groups. Trauma exposure is also reported at high rates among AI individuals and likely confers risk for alcohol use. The purpose of the present study was to examine the effects of assaultive trauma experiences (e.g., physical assault, sexual assault) on alcohol use and alcohol-related consequences in AI adolescents., Methods: We conducted a secondary analysis of self-reported data on trauma exposure, alcohol consumption, and lifetime alcohol-related consequences provided by AI 7th to 12th graders residing on or near a reservation (n = 3498, M age  = 14.8; 49.5% female). Institutional Review Boards, tribal authorities, and school boards approved the study protocols prior to beginning data collection., Results: Nearly half (49.3%, n = 1498) of AI adolescents reported having experienced at least one assaultive trauma in their lifetime. Those who had experienced assaultive trauma were more likely to report lifetime alcohol use (χ 2  = 111.84, p < 0.001) and experienced greater alcohol-related consequences (t(1746) = 12.21, p < 0.001) than those with no assaultive trauma exposure. Multilevel regression analyses indicated that a greater number of assaultive traumatic events was significantly associated with greater odds of lifetime alcohol use (p < 0.001, OR = 1.81, 95% CI [1.65, 2.00]) and having experienced a greater number of alcohol-related consequences (b = 0.36, SE = 0.04, t = 16.95, p < 0.001, 95% CI [0.31, 0.46])., Conclusions: Findings of the present study highlight the relevance of exposure to assaultive trauma to AI adolescents' use of alcohol and experiences of alcohol-related consequences. These findings support the need for trauma-informed interventions in addressing alcohol use among AI adolescents., (© 2022 by the Research Society on Alcoholism.)

Given the disproportionate alcohol-related consequences experienced by North American Indigenous youth, there is a critical need to identify related risk and protective factors. Self-compassion, which has been found to mitigate the effects of trauma exposure, may serve as one such protective factor given the high-degree of historical trauma and contemporary discrimination identified as contributing to the alcohol-related disparities experienced by Indigenous communities. However, no research has examined how self-compassion (i.e., the ability to be kind and accepting and to extend compassion towards oneself) plays a unique role in Indigenous peoples' experiences with alcohol. First Nation adolescents between the ages of 11 and 18 living on a reserve in Eastern Canada ( N =106, M age =14.6, 50.0% female) completed a pencil-and-paper survey regarding their alcohol use, alcohol-related problems, and self-compassion. Self-compassion was significantly inversely associated with alcohol-related problems ( b =-.51, p =.01, 95% CI [-.90, -.12], and significantly interacted with frequency of alcohol use in predicting alcohol-related problems ( b =-.42, p =.04, 95% CI [-.82, -.03]). Simple slopes analyses revealed that the association between frequency of alcohol use and frequency of experiencing alcohol-related problems was significant and positive at low ( b =4.68, p <.001, 95% CI [2.62, 6.73]), but was not significant at high ( b =-.29, p =.89, 95% CI [-4.35, 3.77]) levels of self-compassion. Binary logistic regression revealed that higher scores of self-compassion were associated with a lower odds of being in the high-risk group for AUD (OR=0.90, 95% CI [0.83, 0.98], p =.02). Our results suggest self-compassion may be protective against experiencing alcohol problems in Indigenous youth and thus may be a target for behavioral interventions.

Positive psychology research has led to the development of brief interventions designed to promote positive emotions: positive psychological interventions (PPIs). Randomized controlled trials examining PPIs have found them to be effective in increasing well-being and decreasing depressive symptoms. PPIs have been studied in samples consisting primarily of White Americans; however, PPIs may be useful for members of North American Indigenous groups. PPIs align well with Indigenous views on health, which tend to be strengths-based, holistic, and encompassing the whole body (including the medicine wheel's four dimensions of spirit, mind, heart, and body). This paper provides a framework for the adaptation of PPIs for Indigenous communities and a review of preliminary data on the relationships between positive psychological characteristics and health outcomes including substance use. Implications include the potential widespread impact of culturally adapted PPIs given their alignment with Indigenous thoughts on health and relative ease of administration., (© 2021. Society for Prevention Research.)

Aims: This secondary study characterized components of and engagement in the life-enhancing alcohol-management program (LEAP), which is resident-driven housing first programming., Methods: We used a process akin to conventional content analysis to operationalize the LEAP according to its component activities. We used generalized linear modeling to identify predictors of LEAP activity participation and to predict alcohol and quality-of-life outcomes from participation in specific LEAP activities categories., Results: Overall, 86% of participants attended at least one LEAP activity, which comprised three categories: administrative leadership opportunities, meaningful activities, and pathways to recovery. Employment status alone predicted LEAP activity attendance: Employed residents attended 88% fewer LEAP activities than unemployed residents. Participants who sought out more pathways to recovery activities were more likely daily drinkers and more impacted by alcohol-related harm. Those engaging in administrative leadership opportunities were overall less impacted by alcohol use and had a higher quality of life generally, and their alcohol outcomes further improved over time., Conclusions: Programming developed with Housing First residents was well-attended but could be made more inclusive by including evening programming to accommodate residents employed full time and engaging more severely impacted participants in administrative leadership activities, where the greatest benefits of programming were seen., (© 2020 Wiley Periodicals LLC.)

Infections in adult patients with hematological malignancies (HM) and stem cell transplant (SCT) recipients are a significant cause of morbidity and mortality. A timely diagnosis of infections can have a major impact on outcomes. Tools that help rule out infectious causes of fever can decrease antibiotic use, toxicities, hospitalization costs, and potentially decrease antibiotic resistance in the long term. We retrospectively evaluated the ability of cell-free DNA next-generation sequencing (NGS) testing in the timely identification of pathogenic microorganisms and its impact on the antimicrobial management of immunocompromised patients with hematologic malignancies. In the period between 2018 to 2020, 95 samples were reviewed, of which 31 adult patients (32 tests) had hematologic malignancies or were recipients of SCT. The NGS tests were performed in the following patients: (a) patients with prolonged fever and negative conventional tests, (b) persistent fever despite positive conventional test and appropriate antimicrobials, and (c) fever-free patients with imaging suspicious for infection. The median time from fever to NGS sampling was 5 days (range, 1-28). The median time to NGS results was 2 days (range, 1-6). The NGS resulted in an escalation of antibiotics in 28% of cases (9/32) and de-escalation of antibiotics in 31% of cases (10/32). Overall, NGS testing changed management in nearly 59% (19/32) of patients. The sensitivity and specificity of NGS to detect clinically significant infection was 80% and 58%, respectively. The test identified uncommon and difficult to diagnose organisms such as Nocardia, Legionella, Toxoplasma and Pneumocystis jirovecii resulting in rapid antimicrobial interventions. In conclusion, in patients with HM or SCT recipients, microbial cell-free DNA sequencing allowed rapid and actionable treatment. This strategy can target appropriate antibiotic use, avoid overtreatment, and potentially decrease the hospital length-of-stay., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has resulted in the increased use of cryopreserved grafts for allogeneic hematopoietic cell transplantation (HCT). However, information about the effect of cryopreservation on outcomes for patients receiving allogeneic donor grafts is limited. We evaluated outcomes of HCT recipients who received either fresh or cryopreserved allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) grafts reported to the Center for International Blood and Marrow Transplant Research. A total of 7397 patients were included in the analysis. Recipients of cryopreserved graft were divided into 3 cohorts based on graft source: HLA-matched related PBSC donors (n = 1051), matched unrelated PBSC donors (n = 678), and matched related or unrelated BM donors (n = 154). These patients were propensity score matched with 5514 patients who received fresh allografts. The primary endpoint was engraftment. Multivariate analyses showed no significant increased risk of delayed engraftment, relapse, nonrelapse mortality (NRM), or survival with cryopreservation of BM grafts. In contrast, cryopreservation of related donor PBSC grafts was associated with decreased platelet recovery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68 to 0.78; P < .001) and an increased risk of grade II-IV (HR, 1.27; 95% CI, 1.09 to 1.48; P = .002) and grade III-IV (HR, 1.48; 95% CI, 1.19 to 1.84; P < .001) acute graft-versus-host disease. Cryopreservation of unrelated PBSC grafts was associated with delayed engraftment of neutrophils (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001) and platelets (HR, 0.61; 95% CI, 0.56 to 0.66; P < .001) as well as an increased risk of NRM (HR, 1.4; 95% CI, 1.18 to 1.66; P < .001) and relapse (HR, 1.32; 95% CI, 1.11 to 1.58; P = .002) and decreased progression-free survival (HR, 1.36; 95% CI, 1.20 to 1.55; P < .001) and overall survival (OS) (HR, 1.38; 95% CI, 1.22 to 1.58; P < .001). Reasons for cryopreservation were not routinely collected; however, in a subset of unrelated donor HCT recipients, the reason was typically a change in patient condition. Products cryopreserved for patient reasons were significantly associated with inferior OS in multivariate analysis (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). We conclude that cryopreservation is associated with slower engraftment of PBSC grafts, which may be associated with inferior transplantation outcomes in some patient populations. However, the small numbers in the cryopreserved BM cohort and the lack of information on the reason for cryopreservation in all patients suggests that these data should be interpreted with caution, particularly in the context of the risks associated with unexpected loss of a graft during the pandemic. Future analyses addressing outcomes when cryopreservation is universally applied are urgently required., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

People experiencing homelessness are disproportionately affected by alcohol use disorder (AUD). Abstinence-based treatment, however, does not optimally engage or treat this population. Thus, Harm Reduction Treatment for Alcohol (HaRT-A) was developed together with people with the lived experience of homelessness and AUD and community-based agencies that serve them. HaRT-A is a compassionate and pragmatic approach that aims to help people reduce alcohol-related harm and improve quality of life (QoL) without requiring abstinence or use reduction. The parent RCT showed that HaRT-A precipitated statistically significant reductions in alcohol use, alcohol-related harm, AUD symptoms, and positive urine toxicology tests. This secondary study tested HaRT-A effects on more distal, 6-month pre-to-posttreatment changes on jail and emergency department (ED) utilization. People experiencing homelessness and AUD (N = 168; 24% women) were recruited in community-based clinical and social services settings. Participants were randomized to receive HaRT-A or services as usual. Over four sessions, HaRT-A interventionists delivered three components: (a) collaborative tracking of participant-preferred alcohol metrics, (b) elicitation of harm-reduction and QoL goals, and (c) discussion of safer-drinking strategies. Administrative data on jail and ED utilization were extracted for 6 months pre- and posttreatment. Findings indicated no statistically significant treatment group differences on 6-month changes in jail or ED utilization (ps > .23). Exploratory analyses showed that 2-week frequency of alcohol use was positively correlated with number of jail bookings in the 12 months surrounding their study participation. Additionally, self-reported alcohol-related harm, importance of reducing alcohol-related harm, and perceived physical functioning predicted more ED visits. Future studies are needed to further assess how harm-reduction treatment may be enhanced to move the needle in criminal justice and healthcare utilization in the context of larger samples, longer follow-up timeframes, and more intensive interventions.

Introduction: Substance use among American Indian (AI) adolescents is a significant public health concern, as they report greater health disparities related to substance use compared to other racial/ethnic groups. The present study examines differences across classes of substance use behaviors regarding alcohol- and drug-related consequences., Methods: The current study was a secondary analysis of the dataset used by Stanley and Swaim (2018). AI adolescents (n = 3498, 47.8% female, M age  = 14.8) completed a survey including substance use and related consequences. Protocols were approved by institutional IRB, tribal authority, school boards, and parental consent/child assent were obtained., Results: In line with Stanley and Swaim (2018), we identified four classes of substance use: no past month substance use; marijuana and cigarette use only; alcohol, marijuana, and cigarette use only; and polysubstance use. Cross-class comparisons revealed that adolescents in classes characterized by the use of a greater number of substances also reported experiencing greater alcohol- and drug-related consequences with one exception: the class characterized by marijuana and cigarette use reported greater drug-related consequences compared to the class characterized by alcohol, marijuana, and cigarette use., Conclusions: AI adolescents who engage in the use of multiple substances should be provided with psychoeducation around the increased risk of associated negative consequences. Given the health disparity experienced by AI adolescents, interventions to alleviate the burden of negative consequences are necessary., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Indigenous youth often exhibit high rates of alcohol use and experience disproportionate alcohol-related harm. We examined the moderating role that valuing cultural activities has on the relationship between positive alcohol expectancies and alcohol use and heavy drinking in a sample of Indigenous youth., Method: First Nation adolescents between ages 11 and 18 living on a reserve in eastern Canada (N = 106; mean age = 14.6; 50.0% female) completed a pencil-and-paper survey regarding their positive alcohol expectancies, alcohol use, and beliefs about the importance of cultural activities., Results: A significant interaction was identified between positive alcohol expectancies and valuing cultural activities on past-3-month alcohol use (b = -0.01, SE = 0.001, p < .001) and past-3-month heavy drinking (b = -0.01, SE = 0.001, p < .001). Simple slopes analysis revealed that the association between positive alcohol expectancies and past-3-month alcohol use and heavy drinking was significant for those with low (b = 0.06, SE = 0.007, p < .001; b = 0.07, SE = 0.008, p < .001; respectively) but not high levels of valuing cultural activities (b = 0.01, SE = 0.008, p = .12; b = 0.01, SE = 0.009, p = .08; respectively)., Conclusions: Highly valuing cultural activities may interrupt the relationship between positive alcohol expectancies and alcohol use. This suggests that community interventions and treatment programs targeting alcohol use among Indigenous adolescents should prioritize increasing the value of cultural activities by perhaps making them more available.

Purpose: North American Indigenous (NAI) communities often cite substance misuse as problematic in their communities. The Competing Life Reinforcers (CLRs) model suggests that when reinforcers are valued, important, and incompatible with substance use, they will be associated with less substance misuse. Three categories of CLRs were identified in our formative work and include the following: cultural, social, and extracurricular activities. The aims of the current study were to test the associations among valuing and availability of CLRs and NAI adolescent alcohol and marijuana use., Methods: Adolescents living in rural First Nation reserve communities (N = 106, 50.0% female) reported their substance use and perceived availability and valuing of CLRs (e.g., smudging and after school activities)., Findings: Greater value placed on cultural reinforcers was significantly associated with reduced likelihood of past 3-month drinking to get drunk (OR = 0.85, 95% CI[0.73, 0.98]). Greater value placed on social reinforcers was associated with lower likelihood of past 3-month drinking (OR = 0.94, 95% CI[0.89, 0.995]) and past-3 month drinking to get drunk (OR = 0.94, 95% CI[0.88, 0.99]). Greater valuing extracurricular activities were associated with lower likelihood of past month marijuana use (OR = 0.84, 95% CI[0.72, 098]), past 3-month drinking (OR = 0.77, 95% CI[0.64, 0.92]), and past 3-month drinking to get drunk (OR = 0.76, 95% CI[0.63, 0.92])., Conclusions: CLRs may be protective against NAI adolescent substance use and may be useful targets for prevention and treatment for NAI adolescent substance use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Azacitidine (AZA) maintenance following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) may reduce relapse risk and improve survival. Given logistic and toxicity-related challenges, identifying subgroups appropriate for this approach is an unmet need. Using data from two centers, we retrospectively compared event-free survival (EFS) and overall survival (OS) of AML and MDS patients who received AZA maintenance ( n  = 59) with historic controls ( n  = 90). Controls were selected according to the following criteria: no death, relapse, or Grade III-IV acute GVHD for 100 days after transplant. In multivariable analysis, AZA maintenance yielded significantly improved EFS ( p  = 0.019) and OS ( p  = 0.011). Outcomes differed according to regimen intensity. For reduced-intensity transplant, EFS ( p  = 0.004) and OS ( p  = 0.004) were significantly improved and equivalent to myeloablative transplant. A significant benefit following myeloablative transplant was not observed. Within the limitation of its retrospective nature, this study suggests that AZA maintenance improves outcomes following reduced-intensity HCT, comparable to myeloablative HCT.

Background: Indigenous youth are at increased risk of initiating substance use at early ages and suffer greater negative consequences related to substance use as compared to non-Indigenous youth. Behavioral Theories of Choice suggests that substance use is contingent on the availability of substances and the availability of alternatives to substance use. Objectives: The present study aimed to investigate risk and protective factors associated with substance use in one group of First Nation adolescents. Methods: Using a modified grounded theory approach, the present study conducted qualitative focus groups and individual interviews with fifteen reserve-dwelling (75% female, M age = 15.2 years) First Nation adolescents to assess categories of risk and protective factors based upon Behavioral Theories of Choice. Results: Adolescents identified peer influences, parental/family influences, and community influences and issues as risk and protective factors associated with substance use. Conclusions: Results highlight possible targets of culturally appropriate prevention strategies for Indigenous populations.

Thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small-molecule thrombopoietin receptor agonist that has been approved for use in immune thrombocytopenic purpura and aplastic anemia; but its use after allo-SCT is limited. Between 2014 and 2017, we treated 13 patients with eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation, including 6 patients with primary platelet engraftment failure and 7 with secondary platelet engraftment failure. Eltrombopag was started at an initial dose of 25 or 50 mg per day, and dose adjustments were made in accordance with the manufacturer's recommendation. The cumulative incidence of platelet recovery to ≥50,000/μL without the need for transfusion for at least 7 days was defined as response. The overall response rate was 62% (n = 8). Of the 6 patients with primary isolated platelet failure, 3 (50%) responded, and of the 7 patients with secondary platelet failure, 5 (71%) responded. The median time to response was 33 days (range, 11 to 68 days). In addition, no significant differences in platelet recovery were noted in patients with adequate and decreased bone marrow megakaryocytic reserve (60% and 67%, respectively). Although eltrombopag was well tolerated, and no patient discontinued treatment because of adverse events, only 3 patients were alive at the end of the observation period, with relapse and graft-versus-host disease accounting for majority of the deaths. This suggested that despite the relatively good overall response rate to eltrombopag, inadequate platelet engraftment is a harbinger of poor outcome in allo-SCT., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: People experiencing homelessness are disproportionately affected by alcohol use disorder (AUD). Abstinence-based treatment, however, does not optimally engage or treat this population. Thus, harm reduction treatment for alcohol (HaRT-A) was developed together with people with lived experience of homelessness and AUD and community-based agencies that serve them. HaRT-A is a compassionate and pragmatic approach that aims to help people reduce alcohol-related harm and improve quality of life (QoL) without requiring abstinence or use reduction. A three-month, two-arm randomized controlled trial was conducted to test the initial efficacy of HaRT-A compared to a services-as-usual control condition., Methods: People experiencing homelessness and AUD (N = 168; 24% women) were recruited in community-based clinical and social services settings. Self-reported alcohol use, alcohol-related harm, motivation, and QoL as well as urinary ethyl glucuronide were assessed over a 3-month follow-up. Participants were randomized to receive HaRT-A or services as usual. Over four sessions, HaRT-A interventionists delivered three components: a) collaborative tracking of participant-preferred alcohol metrics, b) elicitation of harm-reduction and QoL goals, and c) discussion of safer-drinking strategies., Results: Compared to control participants, HaRT-A participants reported significantly greater increases in confidence to engage in harm reduction and decreases in peak alcohol use, alcohol-related harm, AUD symptoms, and positive urinary ethyl glucuronide tests (ps < .05). Findings were inconclusive regarding group differences on QoL (ps > .12)., Conclusion: A low-barrier, low-intensity, patient-driven, harm-reduction approach has at least short-term efficacy in improving AUD outcomes in this population. Future studies are needed to establish its longer-term efficacy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Smoking prevalence and mortality is 5 times higher for the chronically homeless versus general population. Unfortunately, traditional smoking cessation treatment does not optimally engage this population. In a preliminary study, smokers experiencing chronic homelessness suggested providers avoid giving advice to quit and instead use a more compassionate, nonjudgmental style to discuss a broader menu of patient-driven options, including safer nicotine use. Most had negative perceptions of smoking cessation medications; however, 76% expressed interest in a switchover to electronic nicotine delivery systems (ENDS). Methods: Using a community-based participatory research approach, we codeveloped harm-reduction treatment for smoking (HaRT-S) together with people with lived experience of chronic homelessness and smoking and a community-based agency that serves them. In HaRT-S, interventionists embody a compassionate, advocacy-oriented "heart-set" and deliver manualized components: a) participant-led tracking of smoking-related outcomes, b) elicitation of harm-reduction goals and progress made toward them, c) discussion of relative risks of nicotine delivery systems, and d) distribution and instructions on use of safer nicotine products. We then conducted a single-arm, 14-week pilot of HaRT-S ( N  = 44). Results: Participants rated procedures "totally acceptable/effective," which was reflected in 26% overrecruitment within a 4-month period and 70% retention at the 14-week follow-up. For each week in the study, participants experienced an 18% increase in odds of reporting 7-day, biochemically verified, point-prevalence abstinence. All participants reporting abstinence used ENDS. Participants evinced reductions in cigarette dependence (-45%), frequency (-29%), and intensity (-78%; p s < .05). Participants who used ENDS experienced an additional 44% reduction in smoking intensity and a 1.2-point reduction in dependence compared to participants who did not. Conclusions: Harm-reduction counseling plus ENDS shows promise for smokers experiencing chronic homelessness. Randomized controlled trials are needed to establish the efficacy of this approach in decreasing smoking-related harm and improving health-related quality of life for this marginalized and disproportionately affected population.

Corticosteroid resistance after acute graft-versus-host disease (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation. Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness because of poor response or excessive toxicity, primarily from infection. α 1 -Antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by downmodulating inflammation and increasing ratios of regulatory (T reg ) to effector T cells (T eff s). In this prospective multicenter clinical study, we sought to determine the safety and response rate of AAT administration in SR-aGVHD. Forty patients with a median age of 59 years received intravenous AAT twice weekly for 4 weeks as first-line treatment of SR-aGVHD. The primary end point was overall response rate (ORR), the proportion of patients with SR-aGVHD in complete (CR) or partial response by day 28 without addition of further immunosuppression. Treatment was well tolerated without drug-related adverse events. A significant increase in serum levels of AAT was observed after treatment. The ORR and CR rates by day 28 were 65% and 35%, respectively, and included responses in all aGVHD target organs. At day 60, responses were sustained in 73% of patients without intervening immunosuppression. Infectious mortality was 10% at 6 months and 2.5% within 30 days of last AAT infusion. Consistent with preclinical data, correlative samples showed an increase in ratio of activated T reg s to T eff s after AAT treatment. These data suggest that AAT is safe and may be potentially efficacious in treating SR-aGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01700036., (© 2018 by The American Society of Hematology.)

Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (⩽2.3 ng/mL, hazard ratio (HR)=5.8, P=0.03) and high (>5.7 ng/mL, HR=5.4, P=0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies.

This study is the first to document suicidality among chronically homeless people with alcohol problems (N = 134) and examine its trajectory following exposure to immediate, permanent, low-barrier housing (i.e., Housing First). Suicidal ideation, intent, plans, and prior attempts were assessed at baseline and during a 2-year follow-up. Baseline suicidal ideation was over four times higher than in the general population. Two-year, within-subjects, longitudinal analyses indicated severity of suicidal ideation decreased by 43% from baseline to follow-up. Significant decreases were also found for intent and clinical significance of ideation. No participants died by suicide during the 2-year follow-up., (© 2016 The American Association of Suicidology.)

Donor leukocyte infusion (DLI) is used to treat relapsed leukemia after allogeneic hematopoietic stem cell transplant (HCT). Data comparing outcomes after unrelated DLI (uDLI) to matched sibling DLI (msDLI) are scant. We performed a retrospective analysis to assess differences in time to administer uDLI versus msDLI, and impact on outcomes. Fifty three patients with relapsed acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) after allogeneic HCT received uDLI (n = 18) or msDLI (n = 35) from 2000 to 2011. Median time from relapse to uDLI request was 15 days (range 0-66). Median time from relapse to uDLI was 56 days versus 40 days for msDLI patients (p = 0.034). 35% of msDLI and 44% of uDLI patients developed acute GVHD (p = 0.50). There was no significant difference in Grade C/D GVHD among uDLI and msDLI (28% and 21%, p = 0.58) or median OS after DLI between uDLI and msDLI (95 versus 75 days, p = 0.76). For patients with relapsed acute leukemia and MDS after allogeneic HCT, time from relapse to uDLI was longer than to msDLI, but incidence of GVHD and overall survival were similar. Access to uDLI does not appear to be a barrier to DLI administration. Outcomes unfortunately remain poor regardless of donor source., (© 2016 Wiley Periodicals, Inc.)

Despite the ongoing advent of more effective immunomodulators and proteasome inhibitors, multiple myeloma (MM) remains incurable and no effective therapy is available for advanced aggressive disease. Although allogeneic (Allo) hematopoietic cell transplantation (HCT) has a curative potential, the outcomes remain poor because of high treatment-related mortality (TRM), mostly due to regimen-related toxicities and graft-versus-host disease (GVHD) in case of myeloablative conditionings, high relapse rate in case of reduced-intensity or nonmyeloablative regimens, and possibly other unknown MM-specific issues. In an attempt to improve TRM, without compromising conditioning intensity, we prospectively explored the feasibility and efficacy of a myeloablative but reduced-toxicity conditioning regimen, consisting of fludarabine and busulfan (FluBu4; fludarabine 40 mg/m(2)/day and busulfan 3.2 mg/kg/day i.v. × 4 days) in 22 patients with high-risk or advanced refractory MM. The majority (14 of 22, 64%) had prior autologous HCT. The median HCT-specific comorbidity index score was 3 (range, 0 to 6), with 46% having a Karnofsky performance score < 80%. Ten patients had unrelated donors, 3 of whom were 7/8 HLA-loci matched. GVHD prophylaxis was tacrolimus and methotrexate in 20 (91%). Most patients had active MM at transplantation, with a partial response in 12 of 22 (46%) and stable disease in 1 of 22 (4.5%). All 22 patients tolerated the FluBu4 conditioning well, without early toxic deaths or graft failure. Common regimen-related toxicities included mild to moderate mucositis (18 of 22, 82%) and mild transient liver function abnormality (9 of 22, 41%). There were no grade 4 toxicities but grade 3 mucositis occurred in 7 of 22 patients (32%). The cumulative incidence of severe, grades III and IV acute GVHD at day 180 was 23% (95% confidence interval [CI], 10% to 47%) and that of chronic GVHD was 68% (95% CI, 46% to 88%). The cumulative incidences of TRM at 100 days, 1 year, and 3 years were 9% (95% CI, 2% to 33%), 19% (95% CI, 7% to 44%), and 29% (95% CI, 13% to 55%), respectively. Two TRMs were due to idiopathic pneumonia syndrome and 1 was due to cirrhosis. They all had decreased pre-HCT corresponding organ function, with HCT-specific comorbidity index scores of > 3. With a median follow-up of 58.7 (range, 39 to 82) months, the cumulative incidences of relapse at 1 and 3 years were 37% (95% CI, 20% to 61%) and 50% (95% CI, 29% to 75%); those for 1-year and 3-year overall survival (OS) were 58% (95% CI, 40% to 83%) and 29% (95% CI, 15% to 57%), respectively, and those for the 1-year and 3-year progression-free survivals (PFS) were 40% (95% CI, 23% to 67%) and 15% (95% CI, 5% to 42%), respectively. In summary, the use of the myeloablative FluBu4 conditioning Allo-HCT for high-risk MM resulted in decreased TRM, compared with that of Allo-HCT using conventional myeloablative regimens; however, the relapse rate was high, including in those developing moderate-to-severe chronic GVHD. This suggested a less robust graft-versus-myeloma effect against high-risk MM, thus resulting in poor PFS and OS. Nonetheless, the FluBu4 regimen may be used as a lower-TRM platform to combine with other strategies, eg, addition of an MM-targeted agent and/or maintenance therapy with these agents, to decrease relapse or progression in patients with high-risk MM., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Bronchiolitis obliterans syndrome (BOS) is a significant post-transplant complication with low survival. BOS stage 0p (BOS 0p) is a parameter detected on pulmonary function tests (PFTs) after lung transplantation to identify patients at risk to develop BOS. We performed a retrospective study on 442 patients who underwent allogeneic stem cell transplant from 2007 to 2011 to evaluate whether development of BOS 0p is a risk factor in this population for BOS. Patients who met criteria for BOS 0p were significantly more likely to develop BOS (hazard ratio [HR], 3.22; P < .001). BOS 0p was significantly associated with a history of lung disease pretransplant (HR, 2.48; P = .001) and chronic graft-versus-host disease (GVHD) outside the lung post-transplant (HR, 23; P < .001). Finally, BOS 0p criteria were adequately sensitive in predicting BOS (85%), with a high negative predictive value (98%). Our findings suggest a routine PFT screening strategy with the intent of detecting BOS 0p, especially among patients with prior lung disease and who developed chronic GVHD, could suitably identify an at-risk population for the development of BOS., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34-0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.

We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after myeloablative allogeneic hematopoietic cell transplantation (HCT). Patients received increasing doses of MAPC (1, 5, or 10 million cells per kilogram recipient weight) as a single i.v. dose on day +2 after HCT (n = 18), or once weekly for up to 5 doses (1 or 5 million cells per kilogram; n = 18). Infusional and regimen-related toxicities were assessed for 30 days after the last MAPC dose. Of 36 allogeneic HCT donors (17 related and 19 unrelated), 35 were 6/6 HLA matched. MAPC infusions were well tolerated without associated infusional toxicity, graft failure, or increased incidence of infection. Median times to neutrophil (n = 36) and platelet (n = 31) engraftment were 15 (range, 11 to 25) and 16 (range, 11 to 41) days, respectively. The overall cumulative incidences of grades II to IV and III and IV acute graft-versus-host disease (GVHD) at day 100 were 37% and 14%, respectively (n = 36). In the group that received the highest single MAPC dose (10 million cells/kg), day 100 incidence of grade II to IV GVHD was 11.1% (1 of 9) with no observed cases of grade III and IV GVHD. We found no evidence for MHC class II allogeneic antibody induction, although some patients showed an increase in serum anticlass I titers compared with baseline. MAPC contribution to blood chimerism was negligible. These phase I data support the safety of stromal stem cell therapy and suggest that MAPC should be tested prospectively as a novel therapeutic option for GVHD prophylaxis after HCT., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Corticosteroids are the accepted primary therapy for acute graft-versus-host disease (GVHD), but durable responses are seen in only about half of the patients. Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0802, a phase 3 multicenter randomized double-blinded trial, was designed to test whether mycophenolate mofetil (MMF) plus corticosteroids was superior to corticosteroids alone as initial therapy for acute GVHD. Patients with newly diagnosed acute GVHD were eligible if they required systemic therapy. Patients were randomized to receive prednisone with either MMF or placebo. The primary end point was acute or chronic GVHD-free survival at day 56 after initiation of therapy. A futility rule for GVHD-free survival at day 56 was met at a planned interim analysis after 235 patients (of 372) were enrolled: 116 MMF, 119 placebo. Baseline characteristics were well balanced between treatment groups including grade and organ distribution of GVHD. GVHD-free survival at day 56, cumulative incidence of chronic GVHD at 12 months, overall survival, Epstein-Barr virus reactivation, severe, life-threatening infections, relapse at 12 months, and quality of life were similar. The addition of MMF to corticosteroids as initial therapy for acute GVHD does not improve GVHD-free survival compared with corticosteroids alone. This trial was registered at www.clinicaltrials.gov as #NCT01002742., (© 2014 by The American Society of Hematology.)

Donor leukocyte infusion (DLI) can induce potent graft-versus-leukemia (GVL) activity in patients with relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, except in patients with chronic-phase chronic myelogenous leukemia, responses to DLI have been disappointing. GVL induction is likely to be most effective in the setting of minimal residual disease. Prevention of relapse through the provision of prophylactic DLI to high-risk patients may improve the outcome of allogeneic HSCT. We previously reported that ex vivo costimulated T cell infusion of activated DLI (aDLI) as treatment for relapse is safe and has potent GVL effects. We hypothesized that prophylactic aDLI can be given safely and prevent relapse in high-risk patients after allogeneic HSCT. Eighteen patients with acute myeolgenous leukemia (n = 14), acute lymphoblastic leukemia (n = 3), or myelodysplastic syndrome (n = 1) underwent allogeneic HSCT after a reduced-intensity conditioning (RIC) regimen with alemtuzumab, fludarabine, and busulfan. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate with a planned early and rapid taper of tacrolimus. Patients without GVHD, off immune suppression, and in remission received aDLI at a dose of 1 × 10(7) CD3(+) cells/kg (aDLI 1) at day +120, followed by a second infusion of 1 × 10(8) CD3 cells/kg (aDLI 2) at day +180. At a median follow-up of 58 months, 5 of the 18 patients (28%) were alive, and 4 patients were in remission. Eleven patients (65%) relapsed, at a median time of 191 days. Twelve of the 18 patients received at least one aDLI, and 6 of these 12 patients also received aDLI 2. Six patients did not receive any aDLI owing to early relapse (n = 2), protocol ineligibility (n = 1), or GVHD (n = 3). Only 2 of the 12 patients who received aDLI 1 developed GVHD. Two out of the 12 patients remain in remission at the time of this report. Disease recurrence was the cause of death in 10 of the 13 patients (77%) who died. Our data indicate that prophylactic ex vivo costimulated CD3/CD28 DLI is safe, feasible, and not associated with significant GVHD. Relapse remains the major cause of treatment failure after RIC HSCT even with rapid withdrawal of immune suppression and the use of prophylactic aDLI, and better strategies to prevent relapse are needed., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Although peripheral blood stem cells (PBSCs) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC versus BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004 to 2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the 2 donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2 to 4 pain as well as grade 2 to 4 toxicities during the pericollection period. In contrast, BM donors were more likely to experience grade 2 to 4 toxicities at 1 week and pain at 1 week and 1 month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, whereas 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female sex. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC versus BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.

Idiopathic Pneumonia Syndrome (IPS) is a common complication after allo-SCT and results in high mortality rates. Conventional treatment for IPS typically includes supportive care and high-dose corticosteroids (CS). Data suggests that TNF-α is important in the pathogenesis of IPS and that the TNF-α inhibitor etanercept may be useful for IPS treatment. We performed a retrospective comparison of consecutive patients treated at our center for IPS with CS only from 1999 to 2003 (group 1, n=22) or CS plus etanercept from 2004 to 2007 (group 2, n=17). In all, 18% of patients in group 1 vs 53% in group 2 were successfully taken off respiratory support and discharged from the hospital (P=0.039). OS was significantly better for recipients of CS plus etanercept (P=0.003). The estimated survival at 28 days and 2 years after IPS was 36.4% (95% CI 17-56%) and 9.1% (95% CI 2-25%) for group 1 and 88.2% (95% CI 61-97%) and 18% (95% CI 4-38%) for group 2, respectively. Our retrospective comparison suggests that the addition of etanercept to CS for IPS improves response rates and OS. However, outcomes remain limited in both groups, highlighting the need for more effective interventions to treat early and late complications of IPS.

We retrospectively analyzed 44 patients undergoing first-line treatment for mantle cell lymphoma with R-HyperCVAD, with or without rituximab (R) maintenance or auto-SCT. The primary study end point was PFS; secondary end point was overall survival.Median follow up for all patients was 3.3 years. Median age was 54 years, and 95% (n=42) were stage III or IV at diagnosis. In all, 17 patients underwent consolidative auto-SCT and 12 patients received R maintenance. The overall response rate was 95%, with 91% achieving complete response (CR). Median PFS for all patients was 3.5 years. Median PFS was 2.3 years for patients treated with R-HyperCVAD alone vs 3.9 years (P=0.02) with R-HyperCVAD+ R maintenance and 4.5 years (P=0.01) with R-HyperCVAD+ auto-SCT. For patients who did not achieve CR at interim staging, PFS for R-HyperCVAD alone was 1.4 years vs not reached for R-HyperCVAD+ consolidation (either R maintenance or auto-SCT) (P=0.02). PFS for patients with CR at interim staging was 3.3 years vs not reached (P=0.04) after consolidation. Our data suggest potential improvement in PFS when R-HyperCVAD is consolidated with either R maintenance or auto-SCT. This benefit appears particularly significant in those patients who do not achieve CR at interim restaging.

Background: Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic hematopoietic stem-cell transplantation (HSCT). The chemokine receptor CCR5 appears to play a role in alloreactivity. We tested whether CCR5 blockade would be safe and limit GVHD in humans., Methods: We tested the in vitro effect of the CCR5 antagonist maraviroc on lymphocyte function and chemotaxis. We then enrolled 38 high-risk patients in a single-group phase 1 and 2 study of reduced-intensity allogeneic HSCT that combined maraviroc with standard GVHD prophylaxis., Results: Maraviroc inhibited CCR5 internalization and lymphocyte chemotaxis in vitro without impairing T-cell function or formation of hematopoietic-cell colonies. In 35 patients who could be evaluated, the cumulative incidence rate (±SE) of grade II to IV acute GVHD was low at 14.7±6.2% on day 100 and 23.6±7.4% on day 180. Acute liver and gut GVHD were not observed before day 100 and remained uncommon before day 180, resulting in a low cumulative incidence of grade III or IV GVHD on day 180 (5.9±4.1%). The 1-year rate of death that was not preceded by disease relapse was 11.7±5.6% without excessive rates of relapse or infection. Serum from patients receiving maraviroc prevented CCR5 internalization by CCL5 and blocked T-cell chemotaxis in vitro, providing evidence of antichemotactic activity., Conclusions: In this study, inhibition of lymphocyte trafficking was a specific and potentially effective new strategy to prevent visceral acute GVHD. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00948753.).

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas that are considered incurable. The role of allogeneic hematopoietic SCT (HSCT) in the treatment of CTCL is not well defined but may provide potent graft-vs-lymphoma (GVL) activity independent of the conditioning therapy. We present outcomes of 12 extensively-pretreated patients with CTCL who underwent allogeneic HSCT using, most commonly, a reduced intensity conditioning regimen. Median age at diagnosis of CTCL was 49 years, and median time to transplantation from diagnosis was 3.3 years. Transplantation induced and maintained CR in six patients with active disease, supporting the presence of a GVL effect. TRM was low, and 42% of patients were alive and disease-free a median duration of 22 months after transplant. Two patients showed strong and direct evidence of a GVL-effect with a direct response to withdrawal of immunosuppression or to donor leukocyte infusion. Our data show that HSCT can provide long-term disease control in patients with advanced CTCL, which otherwise was refractory to immunotherapy and chemotherapy.

Eight centers participated in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303 to determine the effect of extensive T cell depletion (TCD) on the outcome of HLA matched sibling donor transplantation for acute myeloid leukemia. One goal of the study was to determine if TCD could be performed uniformly among study sites. TCD was achieved using the CliniMACS(®) CD34 Reagent System for CD34 enrichment. Processed grafts needed to contain ≥ 2.0 × 10(6) CD34(+)cells/kg with a target of 5.0 × 10(6) CD34(+) cells/kg and <10(5) CD3(+) T cells/kg. Up to 3 collections were allowed to achieve the minimum CD34(+) cell dose. In total, 86 products were processed for 44 patients. Differences in the starting cell products between centers were seen in regard to total nucleated cells, CD34(+) cells, and CD3(+) T cells, which could in part be ascribed to a higher dose of granulocyte-colony stimulating factor used for mobilization early in the trial. Differences between centers in processing outcomes were minimal and could be ascribed to starting cell parameters or to differences in graft analysis methods. Multivariate analysis showed that CD34(+) cell recovery (66.1% ± 20.3%) was inversely associated with the starting number of CD34(+) cells (P = .02). Median purity of the CD34 enriched fraction was 96.7% (61.5%-99.8%) with monocytes and B cells the most common impurity. All patients received the minimum CD34(+) cell dose, and 39 patients (89%) came within 10% or exceeded the target CD34(+) cell dose without exceeding the maximum T cell dose. All patients proceeded to transplantation and all achieved initial engraftment. Products processed at multiple centers using the CliniMACS System for CD34 enrichment were comparably and uniformly highly enriched for CD34(+) cells, with good CD34(+) cell recovery and very low CD3(+) T cell content., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)