A Phase 1 Clinical Trial of NKTR-255 with CD19-22 CAR-T Cell Therapy for Refractory B-cell Acute Lymphoblastic Leukemia.

While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed / refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, nine of whom successfully received CAR19-22 followed by NKTR-255. There were no dose limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with eight out of nine patients (89%) achieving measurable residual disease negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).

LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.

Mutations in five canonical Ras pathway genes (NF1, NRAS, KRAS, PTPN11 and CBL) are detected in nearly 90% of patients with juvenile myelomonocytic leukemia (JMML), a frequently fatal malignant neoplasm of early childhood. In this report, we describe seven patients diagnosed with SH2B3-mutated JMML, including five patients who were found to have initiating, loss-of-function mutations in the gene. SH2B3 encodes the adaptor protein LNK, a negative regulator of normal hematopoiesis upstream of the Ras pathway. These mutations were identified to be germline, somatic or a combination of both. Loss of function of LNK, which has been observed in other myeloid malignancies, results in abnormal proliferation of hematopoietic cells due to cytokine hypersensitivity and activation of the JAK/STAT signaling pathway. In vitro studies of induced pluripotent stem cell-derived JMML-like hematopoietic progenitor cells also demonstrated sensitivity of SH2B3-mutated hematopoietic progenitor cells to JAK inhibition. Lastly, we describe two patients with JMML and SH2B3 mutations who were treated with the JAK1/2 inhibitor ruxolitinib. This report expands the spectrum of initiating mutations in JMML and raises the possibility of targeting the JAK/STAT pathway in patients with SH2B3 mutations.

Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry.

BACKGROUND: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. METHODS: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years). RESULTS: Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up. CONCLUSIONS: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.

Physical examination of the female cancer patient with sexual concerns: What oncologists and patients should expect from consultation with a specialist.

Answer questions and earn CME/CNE Sexual concerns are prevalent in women with cancer or cancer history and are a factor in patient decision making about cancer treatment and risk-reduction options. Physical examination of the female cancer patient with sexual concerns, regardless of the type or site of her cancer, is an essential and early component of a comprehensive evaluation and effective treatment plan. Specialized practices are emerging that focus specifically on evaluation and treatment of women with cancer and sexual function problems. As part of a specialized evaluation, oncologists and their patients should expect a thorough physical examination to identify or rule out physical causes of sexual problems or dysfunction. This review provides oncology professionals with a description of the physical examination of the female cancer patient with sexual function concerns. This description aims to inform anticipatory guidance for the patient and to assist in interpreting specialists' findings and recommendations. In centers or regions where specialized care is not yet available, this review can also be used by oncology practices to educate and support health care providers interested in expanding their practices to treat women with cancer and sexual function concerns. CA Cancer J Clin 2016;66:241-263. © 2016 American Cancer Society.

Frontline treatment patterns and outcomes among older adults with acute myeloid leukemia: A population-based analysis in the modern era.

BACKGROUND: Traditionally, conventional induction chemotherapy has been the primary frontline treatment for acute myeloid leukemia (AML); however, older adults are often poor chemotherapy candidates. Recently, several nonconventional frontline AML regimens, including hypomethylating agents, the BCL-2 inhibitor venetoclax, and targeted therapies, have emerged, and they may offer new options for older adults. This study was aimed at describing treatment patterns and outcomes of older adult AML in a modern population-based cohort. METHODS: This study evaluated patients aged ≥60 years with a first primary diagnosis of AML (2014-2017) in the California Cancer Registry linked to inpatient hospitalizations. Multivariable regression examined factors associated with the frontline treatment regimen and survival. RESULTS: In all, 3068 patients were included; 36% received frontline therapy with a conventional chemotherapy backbone, 42% received nonconventional therapy, and 22% received no treatment. The use of nonconventional therapy increased over time from 38% of patients in 2014 to 47% in 2017 (P < .001). In multivariable analyses, receipt of treatment was associated with an age younger than 80 years, fewer than 2 comorbidities, and care at a National Cancer Institute-designated cancer center (NCI-CC). Compared with conventional chemotherapy, nonconventional therapy was associated with Black race/ethnicity, public health insurance, fewer hospital admissions, and fewer inpatient days. Receiving frontline therapy at an NCI-CC was independently associated with superior overall survival. CONCLUSIONS: Using a population-based approach, this study has demonstrated that patterns of care for frontline AML treatment in older adults are changing, with increasing use of nonconventional therapies. A significant proportion of older adults remain untreated. At the population level, there remain opportunities to increase therapy access for older adults with AML.

Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent.

We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.

Symptomatic presentation of cervical cancer in emergency departments in California.

PURPOSE: Through screening and HPV vaccination, cervical cancer can mostly be prevented or detected very early, before symptoms develop. However, cervical cancer persists, and many women are diagnosed at advanced stages. Little is known about the degree to which U.S. women may begin their diagnostic workup for cervical cancer in Emergency Departments (ED). We sought to quantify the proportion of women presenting symptomatically in the ED prior to their diagnosis with cervical cancer and to describe their characteristics and outcomes. METHODS: We identified women diagnosed from 2006 to 2017 with cervical cancer in the California Cancer Registry. We linked this cohort to statewide ED discharge records to determine ED use and symptoms present at the encounter. Multivariable logistic regression models examined associations with ED use and multivariable Cox proportional hazards regression models examined associations with survival. RESULTS: Of the more than 16,000 women with cervical cancer in the study cohort, 28% presented symptomatically in the ED prior to diagnosis. Those presenting symptomatically were more likely to have public (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.06-1.27) or no insurance (OR 4.81; CI 4.06-5.71) (vs. private), low socioeconomic status (SES) (OR 1.76; CI 1.52-2.04), late-stage disease (OR 5.29; CI 4.70-5.96), and had a 37% increased risk of death (CI 1.28-1.46). CONCLUSION: Nearly a third of women with cervical cancer presented symptomatically, outside of a primary care setting, suggesting that many women, especially those with low SES, may not be benefiting from screening or healthcare following abnormal results.

Optimizing Antithymocyte Globulin Dosing for Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Based on Recipient Absolute Lymphocyte Count.

Antithymocyte globulin (ATG) is used as prophylaxis against graft-versus-host disease (GVHD). Current dosing regimens for ATG are empiric and weight-based, and do not account for patient-specific factors. Furthermore, the target of ATG, recipient T cells post-cytotoxic chemotherapy, is not a function of recipient weight. We hypothesized the recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration would interact with the dose of ATG administered to predict transplantation outcomes. We retrospectively analyzed 135 patients who received ATG for GVHD prophylaxis for unrelated allogeneic hematopoietic cell transplantation at 3 different doses: 10 mg/kg, 7.5 mg/kg, and 5 mg/kg. There was no difference in 2-year overall survival (OS) among ATG dosing groups; however, deaths from infectious complications were significantly higher with higher doses of ATG (3.7% versus 19% versus 26.7%; P = .02). Severity of chronic GVHD was lower with higher doses of ATG (28% versus 24% versus 4%; P = .03). In multivariate analysis, the median peripheral blood ALC on day of ATG administration and the total amount of ATG interacted to predict OS (hazard ratio, .09; P = .03). For low recipient ALC (10th percentile, or .56 × 102/µL), a higher total ATG dose was associated with a greater risk of death, whereas for high recipient ALC (90th percentile, or 24.96 × 102/µL), a higher ATG dose was associated with a lower risk of death. Our findings suggest that the interaction between ATG and its target, the recipient lymphocyte, could represent a new paradigm for ATG dosing.

Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia.

Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.

Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and Rituximab Is Associated with Improved Outcomes Compared with Fludarabine and Busulfan after Allogeneic Stem Cell Transplantation for B Cell Malignancies.

Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab-containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined. We retrospectively analyzed 94 patients who received an allogeneic transplant for a B cell lymphoid malignancy. Of these, 33 received RIC with fludarabine, cyclophosphamide, and rituximab (FCR) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin inhibitor and mini-methotrexate, and 61 received RIC with fludarabine and busulfan (FluBu) and GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The 2-year overall survival was superior in patients who received FCR versus FluBu (72.7% versus 54.1%, P = .031), and in multivariable analysis adjusted for Disease Risk Index and donor type, only the conditioning regimen (FluBu versus FCR: HR, 2.06; 95% CI, 1.04 to 4.08; P = .037) and Disease Risk Index (low versus intermediate/high: HR, .38; 95% CI, .17 to .86; P = .02) were independent predictors of overall survival. The 2-year cumulative incidence of chronic GVHD was lower in patients who received FCR versus FluBu (24.2% versus 51.7%, P = .01). There was no difference in rate of relapse/progression or acute GVHD. Our results demonstrate that the use of RIC with FCR and GVHD prophylaxis with a calcineurin inhibitor and mini-methotrexate is associated with decreased chronic GVHD and improved overall survival.

Does adherence to epilepsy quality measures correlate with reduced epilepsy-related adverse hospitalizations? A retrospective experience.

In 2011, the American Academy of Neurology (AAN) established eight epilepsy quality measures (EQMs) for chronic epilepsy treatment to address deficits in quality of care. This study assesses the relationship between adherence to these EQMs and epilepsy-related adverse hospitalizations (ERAHs). A retrospective chart review of 475 new epilepsy clinic patients with an ICD-9 code 345.1-9 between 2010 and 2012 was conducted. Patient demographics, adherence to AAN guidelines, and annual number of ERAHs were assessed. Fisher's exact test was used to assess the relationship between adherence to guidelines (as well as socioeconomic variables) and the presence of one or more ERAH per year. Of the eight measures, only documentation of seizure frequency, but not seizure type, correlated with ERAH (relative risk [RR] 0.343, 95% confidence interval [CI] 0.176-0.673, p = 0.010). Among patients in the intellectually disabled population (n = 70), only review/request of neuroimaging correlated with ERAH (RR 0.128, 95% CI 0.016-1.009, p = 0.004). ERAHs were more likely in African American patients (RR 2.451, 95% CI 1.377-4.348, p = 0.008), Hispanic/Latino patients (RR 4.016, 95% CI 1.721-9.346, p = 0.016), Medicaid patients (RR 2.217, 95% CI 1.258-3.712, p = 0.009), and uninsured patients (RR 2.667, 95% CI 1.332-5.348, p = 0.013). In this retrospective series, adherence to the eight AAN quality measures did not strongly correlate with annual ERAH.

Can you ask? We just did! Assessing sexual function and concerns in patients presenting for initial gynecologic oncology consultation.

OBJECTIVES: To describe patterns of response to, and assess sexual function and activity elicited by, a self-administered assessment incorporated into a new patient intake form for gynecologic oncology consultation. METHODS: A cross-sectional study of patients presenting to a single urban academic medical center between January 2010 and September 2012. New patients completed a self-administered intake form, including six brief sexual activity and function items. These items, along with abstracted medical record data, were descriptively analyzed. Logistic regression was used to assess the association between sexual activity and function and disease status, adjusting for age. RESULTS: Median age was 50 years (range 18-91, N=499); more than half had a final diagnosis of cancer. Most patients completed all sex-related items on the intake form; 98% answered at least one. Among patients who were sexually active in the prior 12 months (57% with cancer, 64% with benign disease), 52% indicated on the intake form having, during that period, a sexual problem lasting several months or more. Of these, 15% had physician documentation of the sexual problem. Eighteen women were referred for care. Providers reported no patient complaints about the inclusion of sexual items on the intake form. CONCLUSIONS: Nearly all new patients presenting for gynecologic oncology consultation answered self-administered items to assess sexual activity and function. Further study is needed to determine the role of pre-treatment identification of sexual function concerns in improving sexual outcomes associated with cancer diagnosis and treatment.

Hyaluronan contributes to bronchiolitis obliterans syndrome and stimulates lung allograft rejection through activation of innate immunity.

RATIONALE: Although innate immunity is increasingly recognized to contribute to lung allograft rejection, the significance of endogenous innate ligands, such as hyaluronan (HA) fragments, in clinical or experimental lung transplantation is uncertain. OBJECTIVES: To determine if HA is associated with clinical bronchiolitis obliterans syndrome (BOS) in lung transplant recipients, and evaluate the effect of low- or high-molecular-weight HA on experimental lung allograft rejection, including dependence on innate signaling pathways or effector cells. METHODS: HA concentrations were measured in bronchoalveolar lavage and plasma samples from lung recipients with or without established BOS. BOS and normal lung tissues were assessed for HA localization and expression of HA synthases. Murine orthotopic lung recipients with established tolerance were treated with low- or high-molecular-weight HA under varied experimental conditions, including Toll-like receptor (TLR) 2/4 and myeloid differentiation protein 88 deficiency and neutrophil depletion. MEASUREMENTS AND MAIN RESULTS: HA localized within areas of intraluminal small airways fibrosis in BOS lung tissue. Moreover, transcripts for HA synthase enzymes were significantly elevated in BOS versus normal lung tissues and both lavage fluid and plasma HA concentrations were increased in recipients with BOS. Treatment with low-molecular-weight HA abrogated tolerance in murine orthotopic lung recipients in a TLR2/4- and myeloid differentiation protein 88-dependent fashion and drove expansion of alloantigen-specific T lymphocytes. Additionally, TLR-dependent signals stimulated neutrophilia that promoted rejection. In contrast, high-molecular-weight HA attenuated basal allograft inflammation. CONCLUSIONS: These data suggest that accumulation of HA could contribute to BOS by directly activating innate immune signaling pathways that promote allograft rejection and neutrophilia.

Assessment of bowel function in the peripartum period.

PURPOSE: Obstetric patients frequently experience changes in bowel function, throughout pregnancy and into the postpartum period. Little is known regarding the timing and consistency of bowel movements immediately postpartum. The primary aim of this study was to characterize the timing and consistency of the first bowel movement after obstetric delivery in a racially diverse population at an academic medical center. METHODS: Patients were approached on the day of delivery. Patients received a data collection survey to record the date and consistency of their first bowel movement. Consistency was assessed using the Bristol Stool Form Scale. RESULTS: One hundred and sixty-nine patients were enrolled and 101 completed surveys were returned, for a response rate of 59%. The average number of days to first bowel movement was 1.55 versus 3.38 (p < 0.01), for vaginal delivery and cesarean section, respectively. Univariate analysis revealed cesarean delivery (+1.79 days, p < 0.01) and breastfeeding (-0.64 days, p = 0.01) as independent factors affecting the timing of the first bowel movement. CONCLUSIONS: Both route of delivery and breastfeeding status may affect timing and consistency of the first bowel movement after obstetric delivery.

Long-Term Clinical Outcomes and B Cell Immune Reconstitution Following Allo-HCT With Prophylactic, Post-Transplant Rituximab.

Chronic graft-versus-host disease (cGVHD) remains a significant source of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Post-transplant, prophylactic rituximab has successfully decreased cGHVD rates in clinical trials, but the durability of this strategy is uncertain. The long-terms effect of post-HCT B cell depletion on immune reconstitution, B cell function, and infectious complications are also unknown. In this study, we provide 10 yr follow-up and correlative analyses on patients given post-HCT, prophylactic rituximab. The objective of the study is to examine the durability of cGVHD protection as well as the long-term effect of rituximab prophylaxis on protective immune reconstitution, B cell function, and alloantibody formation. We analyzed 35 patients given prophylactic rituximab on phase II clinical trial. Clinical outcomes included cGVHD development, relapse and survival outcomes, and infectious outcomes. Correlative analyses included B cell subset analysis, development of antibodies to infectious antigens, and, for male patients receiving female donor grafts, development of antibodies to HY antigens. To further investigate the effect of rituximab on immune reconstitution and function, we also analyzed 43 similarly transplanted patients who did not receive post- or peri-HCT rituximab as a comparator group. For patients who received rituximab, the 8-yr cumulative incidence of cGHVD and freedom from immunosuppression were 20.0% and 76.2%, respectively. Importantly, no late incidences of cGVHD developed beyond 14 mo post-HCT. Relative to patients who did not receive rituximab, post-HCT rituximab was associated with increased B cell aplasia at 1 yr post-HCT (42.9% versus 11% of patients, P = .037); by 3 yr post-HCT, this aplasia resolved. Patients who received rituximab also had a significantly lower proportion of IgD+/CD38+ transitional B cells at 3 yr post-HCT (78.8% versus 89.9%, P = .039); at 10 yr post-HCT, this percentage remained markedly decreased at 50.7%. Rituximab prophylaxis altered B cell function. In male patients receiving female donor grafts, fewer patients developed HY antibodies at 3 yr post-HCT (20% versus 78%, P = .04). At 10 yr post-HCT, HY antibody production remained decreased at 33%. Rituximab prophylaxis was also associated with significantly lower antibody response to tetanus and EBV infectious antigens as well as lower IgG levels. Despite these changes, post-HCT was not associated with increased infections, although patients who received rituximab required intravenous immunoglobulin (IVIG) supplementation more frequently than those who did not (62.9% versus 32.6% of patients, P = .01). Prior data on the efficacy and feasibility of rituximab prophylaxis are durable, with persistent reduction in cGVHD. Rituximab prophylaxis also results in lasting B cell immunologic changes, with altered B cell subset composition and decreased alloantibody formation. Associated infectious risks were not increased, perhaps mitigated by high IVIG use.

Measurable residual disease conversion rate with consolidation chemotherapy in acute myeloid leukemia.

The rate of MRD clearance in AML with standard consolidation chemotherapy is not well defined. A multi-institution retrospective analysis was performed on 107 consecutively treated AML patients in morphologic complete remission with detectable MRD post-induction therapy who received standard chemotherapy consolidation. In response to standard intermediate/high-dose cytarabine consolidation therapy, 26 of 60 patients (43.3%) with MRD threshold of detection of at least 0.1% converted to MRD-negative status (undetectable with assay used), and 6 of 47 patients (12.8%) with MRD threshold of detection > 0.1% converted to MRD-negative status. Multivariable logistic regression for patients with MRD threshold of detection of at least 0.1% showed that, when controlling for age, ELN risk category, dose of cytarabine, and use of a combination agent, treatment with 1 cycle of consolidation cytarabine versus ≥2 cycles decreased the odds of conversion of AML to MRD-negative (OR = 0.24, 95% CI 0.07-0.85, p = 0.03).

Alcohol consumption and sport: a cross-sectional study of alcohol management practices associated with at-risk alcohol consumption at community football clubs.

BACKGROUND: Excessive alcohol consumption is responsible for considerable harm from chronic disease and injury. Within most developed countries, members of sporting clubs participate in at-risk alcohol consumption at levels above that of communities generally. There has been limited research investigating the predictors of at-risk alcohol consumption in sporting settings, particularly at the non-elite level. The purpose of this study was to examine the association between the alcohol management practices and characteristics of community football clubs and at-risk alcohol consumption by club members. METHODS: A cross sectional survey of community football club management representatives and members was conducted. Logistic regression analysis (adjusting for clustering by club) was used to determine the association between the alcohol management practices (including alcohol management policy, alcohol-related sponsorship, availability of low- and non-alcoholic drinks, and alcohol-related promotions, awards and prizes) and characteristics (football code, size and location) of sporting clubs and at-risk alcohol consumption by club members. RESULTS: Members of clubs that served alcohol to intoxicated people [OR: 2.23 (95% CI: 1.26-3.93)], conducted 'happy hour' promotions [OR: 2.84 (95% CI: 1.84-4.38)] or provided alcohol-only awards and prizes [OR: 1.80 (95% CI: 1.16-2.80)] were at significantly greater odds of consuming alcohol at risky levels than members of clubs that did not have such alcohol management practices. At-risk alcohol consumption was also more likely among members of clubs with less than 150 players compared with larger clubs [OR:1.45 (95% CI: 1.02-2.05)] and amongst members of particular football codes. CONCLUSIONS: The findings of this study suggest a need and opportunity for the implementation of alcohol harm reduction strategies targeting specific alcohol management practices at community football clubs.