Transplant Eligible and Ineligible Elderly Patients with AML-A Genomic Approach and Next Generation Questions.

The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies. In this review, we discuss recent modifications suggested by European Leukemia Network 2022 (ELN-2022) risk stratification and review recent aging cell biology advances with the discussion of four AML cases. While an older age, >60 years, does not constitute an absolute contraindication for allo-HCT, the careful patient selection based on a detailed and multidisciplinary risk stratification cannot be overemphasized.

Precision Immuno-Oncology in NSCLC through Gender Equity Lenses.

Precision immuno-oncology involves the development of personalized cancer treatments that are influenced by the unique nature of an individual's DNA, immune cells, and their tumor's molecular characterization. Biological sex influences immunity; females typically mount stronger innate and adaptive immune responses than males. Though more research is warranted, we continue to observe an enhanced benefit for females with lung cancer when treated with combination chemoimmunotherapy in contrast to the preferred approach of utilizing immunotherapy alone in men. Despite the observed sex differences in response to treatments, women remain underrepresented in oncology clinical trials, largely as a result of gender-biased misconceptions. Such exclusion has resulted in the development of less efficacious treatment guidelines and clinical recommendations and has created a knowledge gap in regard to immunotherapy-related survivorship issues such as fertility. To develop a more precise approach to care and overcome the exclusion of women from clinical trials, flexible trial schedules, multilingual communication strategies, financial, and transportation assistance for participants should be adopted. The impact of intersectionality and other determinants of health that affect the diagnosis, treatment, and outcomes in women must also be considered in order to develop a comprehensive understanding of the unique impact of immunotherapy in all women with lung cancer.

Presentation and Management of the Pediatric Trigger Finger: A Multicenter Retrospective Cohort Study.

PURPOSE: Pediatric trigger finger (PTF) is an acquired condition that is uncommon and anatomically complex. Currently, the literature is characterized by a small number of retrospective case series with limited sample sizes. This investigation sought to evaluate the presentation, management, and treatment outcomes of PTF in a large, multicenter cohort. METHODS: A retrospective review of pediatric patients with a diagnosis of PTF between 2009 and 2020 was performed at three tertiary referral hospitals. Patient demographics, PTF characteristics, treatment strategies, and outcomes were abstracted from the electronic medical records. Patients and families also were contacted by telephone to assess the downstream persistence or recurrence of triggering symptoms. RESULTS: In total, 321 patients with 449 PTFs were included at a mean follow-up of 3.9 ± 4.0 years. There were approximately equal numbers of boys and girls, and the mean age of symptom onset was 5.4 ± 5.1 years. The middle (34.7%) and index (11.6%) fingers were the most and least commonly affected digits, respectively. Overall, PTFs managed operatively achieved significantly higher rates of complete resolution compared with PTFs managed nonsurgically (97.1% vs 30.0%). Seventy-five percent of PTFs that achieved complete resolution with nonsurgical management did so within 6 months, and approximately 90% did so within 12 months. Patients with multidigit involvement, higher Quinnell grade at presentation, or palpable nodularity were significantly more likely to undergo surgery. There was no significant difference in the rate of complete resolution between splinted versus not splinted PTFs or across operative techniques. CONCLUSIONS: Only 30% of the PTFs managed nonsurgically achieved complete resolution. Splinting did not improve resolution rates in children treated nonsurgically. In contrast, surgical intervention has a high likelihood of restoring motion and function of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

NSCLC With Synchronous EGFR Mutations in Li Fraumeni Syndrome: A Case Report.

We report a case of a patient with Li Fraumeni Syndrome (LFS) who developed synchronous EGFR exon deletion 19 and EGFR exon 20 insertion NSCLC and characterize the diagnostic and therapeutic challenges in managing her care. Osimertinib was effective in the EGFR deletion 19 population but did not garner a response in the EGFR exon 20 insertion population, which was treated definitively with surgical resection. At the time of oligoprogression, she underwent surgical resection, and radiation therapy was minimized. The biologic link between LFS and EGFR mutation remains unclear, and using larger, real-world cohorts could help to clarify the relationship between LFS and EGFR-mutant NSCLC.

Predictors for operative treatment in pediatric proximal third both-bone diaphyseal forearm fractures in children include age and translation, but not initial angulation.

Introduction: Proximal third diaphyseal fractures of the radius and ulna represent an onerous fracture pattern due to difficulty maintaining acceptable alignment with nonoperative management. Our aim was to identify the factors that increase the odds for a surgical treatment of these fractures. Recognizing these factors can raise awareness to patients who are more likely to require additional care and assist clinicians in counseling families, targeting treatment plans, and constructing follow-up protocols. We hypothesized that the age of the patient, the amount of initial fracture displacement, and the angulation of the fracture would predict the need for operative treatment. Methods: We retrospectively reviewed 276 proximal third diaphyseal forearm fractures at a single tertiary care institution. All patients underwent a nonoperative treatment trial, and if failed continued to surgery. Following a univariate analysis, we constructed a binary multivariate logistic regression model that included age, initial translation, and initial angulation to assess the association between the tested variables. Results: A regression model revealed that age (10 years and older, odds ratio: 8.2, 95% confidence interval: 3.9-17.24, p < 0.001) and radius translation of more than 100% (odds ratio: 7.06, 95% confidence interval: 2.69-18.52, p < 0.001) were associated with the need for surgical treatment. Initial fracture angulation lacked an association with a surgical treatment (odds ratio: 0.81 95% confidence interval: 0.38-1.74, p = 0.59). Conclusion: Age above 10 years and 100% initial translation of the radius fracture increased the odds for an ultimate decision to perform a surgery. Initial angulation, although often being the most remarkable radiographic feature, was not associated with a nonoperative treatment failure. We recommend an initial reduction attempt after counseling patients and their families that there is a high rate of conversion to operative treatment when the above features are met. Level of evidence: level III.

TP53 in AML and MDS: The new (old) kid on the block.

MDS and AML are clonal hematopoietic stem cell disorders of increasing incidence, having a variable prognosis based, among others, on co-occurring molecular abnormalities. TP53 mutations are frequently detected in these myeloid neoplasms and portend a poor prognosis with known therapeutic resistance. This article provides a timely review of the complexity of TP53 alterations, providing updates in diagnosis and prognosis based on new 2022 International Consensus Classification (ICC) and World Health Organization (WHO) guidelines. The article addresses optimal testing strategies and reviews current and arising therapeutic approaches. While the treatment landscape for this molecular subgroup is under active development, further exploration is needed to optimize the care of this group of patients with unmet needs.

Remarkable Intracranial Response to Sotorasib in a Patient With KRAS G12C-Mutated Lung Adenocarcinoma and Untreated Brain Metastases: A Case Report.

Sotorasib is a KRAS G12C inhibitor that recently received approval for use in locally advanced or metastatic KRAS G12C-mutated NSCLC. CodeBreaK100, the phase 2 clinical trial leading to the approval of sotorasib, excluded patients with untreated brain metastases; there have been no reports describing efficacy of sotorasib on untreated brain metastases. We present a case of a patient with active untreated brain metastases with resulting disorientation and weakness who has radiographic response and complete resolution of neurologic symptoms with sotorasib. Our case illustrates the intracranial activity of sotorasib, but additional studies are needed to characterize the intracranial response rate and duration of response in these patients.

Antibody-Drug Conjugates in Non-Small Cell Lung Cancer: Emergence of a Novel Therapeutic Class.

PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) are a class of therapeutics that combine target-specific monoclonal antibodies with cytotoxic chemotherapy. Here, we describe the components of ADCs and review their promising activity, safety, and applicability in non-small cell lung cancer (NSCLC). RECENT FINDINGS: Technological advancements have reinvigorated ADCs as a viable treatment strategy in advanced solid tumors. Several target-specific ADCs have shown promise in treatment-refractory NSCLC, including agents targeting HER2, HER3, TROP2, CEACAM5, and MET, among others, with multiple confirmatory phase 3 trials ongoing. Critically, ADCs have demonstrated efficacy signals in both driver mutation-positive and mutation-negative advanced NSCLC, reinforcing their potential as an efficacious treatment strategy that transcends diverse tumor biology in advanced NSCLC. ADCs are a promising class of anti-cancer therapeutics that have significant potential in advanced NSCLC. Beyond confirmatory phase 3 trials, several questions remain including optimal agent sequencing, combinatorial methods, and unique toxicity management.

Oral Glucose Tolerance Test Measures of First-phase Insulin Response and Their Predictive Ability for Type 1 Diabetes.

CONTEXT: Decreased first-phase insulin response (FPIR) during intravenous glucose tolerance testing (IVGTT) is an early indicator of ß-cell dysfunction and predictor of type 1 diabetes (T1D). OBJECTIVE: Assess whether oral glucose tolerance test (OGTT) measures could serve as FPIR alternatives in their ability to predict T1D in autoantibody positive (Aab+) subjects. DESIGN: OGTT and IVGTT were performed within 30 days of each other. Eleven OGTT variables were evaluated for (1) correlation with FPIR and (2) T1D prediction. SETTING: Type 1 Diabetes TrialNet "Oral Insulin for Prevention of Diabetes in Relatives at Risk for T1D" (TN-07) and Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) studies clinical sites. PATIENTS: TN-07 (n = 292; age 9.4 ±â€…6.1 years) and DPT-1 (n = 194; age 15.1 ±â€…10.0 years) Aab + relatives of T1D individuals. MAIN OUTCOME MEASURES: (1) Correlation coefficients of OGTT measures with FPIR and (2) T1D prediction at 2 years using area under receiver operating characteristic (ROCAUC) curves. RESULTS: Index60 showed the strongest correlation in DPT-1 (r = -0.562) but was weaker in TN-07 (r = -0.378). C-peptide index consistently showed good correlation with FPIR across studies (TN-07, r = 0.583; DPT-1, r = 0.544; P < 0.0001). Index60 and C-peptide index had the highest ROCAUCs for T1D prediction (0.778 vs 0.717 in TN-07 and 0.763 vs 0.721 in DPT-1, respectively; P = NS), followed by FPIR (0.707 in TN-07; 0.628 in DPT-1). CONCLUSIONS: C-peptide index was the strongest measure to correlate with FPIR in both studies. Index60 and C-peptide index had the highest predictive accuracy for T1D and were comparable. OGTTs could be considered instead of IVGTTs for subject stratification in T1D prevention trials.

T-Cell Receptor Gene Rearrangement Clonality, Flow Cytometry Status, and Associated Outcomes in Early-Stage Cutaneous T-Cell Lymphoma.

IMPORTANCE: The prognostic significance of clonal T-cell receptor (TCR) rearrangement or low-level blood involvement as assessed by flow cytometry for patients with early-stage cutaneous T-cell lymphoma (CTCL) is not clear. OBJECTIVE: To assess the association of low-level blood involvement by TCR clonality and flow cytometry with outcomes for patients with early-stage CTCL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort analysis was conducted from September 1, 2019, to February 29, 2020, of 322 patients with early-stage (I-IIA) CTCL seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital. T-cell receptor gene rearrangement and flow cytometry records from the peripheral blood were documented at initial assessment. EXPOSURES: T-cell receptor clonality and peripheral blood flow cytometry. MAIN OUTCOMES AND MEASURES: Univariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival (OS) and time to next treatment. The primary outcome was OS from diagnosis and time to next treatment, and the hypotheses were formulated prior to data collection. RESULTS: A total of 322 patients (166 female patients [51.6%]; median age at diagnosis, 53.8 years [range, 8.6-87.4 years]) with early-stage CTCL diagnosed from 1990 to 2018 were identified; of these, 258 had data available for both flow cytometry and TCR. Positive results for both TCR clonality and flow cytometry were associated with inferior OS in early-stage CTCL compared with both having negative results (hazard ratio [HR], 2.86; 95% CI, 1.02-8.06; P = .046). Positive results for only TCR clonality or only flow cytometry were not associated with OS (TCR clonality: HR, 1.31; 95% CI, 0.70-2.47; P = .40; flow cytometry: HR, 1.21; 95% CI, 0.58-2.52; P = .61) or time to next treatment (TCR clonality: HR, 1.05; 95% CI, 0.77-1.43; P = .76; flow cytometry: HR, 0.74; 95% CI, 0.47-1.16; P = .12). However, positive flow cytometry results were associated with reduced OS in the stage IIA subgroup (n = 94; HR, 1.17; 95% CI, 1.18-8.74; P = .02). Covariates associated with reduced survival included advanced age at diagnosis, male sex, and higher disease stage. CONCLUSIONS AND RELEVANCE: This cohort study of patients with early-stage CTCL suggests that low-level blood involvement as indicated by positive results for both TCR gene rearrangement and flow cytometry was associated with inferior OS, whereas positive results for either flow cytometry or TCR clonality was not. More precise measurements of blood involvement in CTCL and larger multi-institutional cohorts are needed to validate the prognostic significance of low-level blood involvement in early-stage CTCL.

Socioeconomic Factors Influence the Impact of Tumor HPV Status on Outcome of Patients With Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: Human papilloma virus (HPV) association remains one of the most important predictors of clinical outcome in oropharyngeal squamous cell carcinoma (OPSCC). We aimed to determine whether the relationship between HPV status and overall survival was influenced by socioeconomic factors. MATERIALS AND METHODS: Using the National Cancer Database, we examined the relationship between socioeconomic status and overall survival, controlling for demographics and socioeconomic variables (age at diagnosis, race, sex, clinical stage, facility type, facility location, insurance status, median-income quartiles, percent of no high-school education quartiles, rural-urban dwelling, Charlson-Deyo score, primary site, and treatment type). RESULTS: HPV-positive patients with private insurance have improved overall survival compared with HPV-positive patients who are uninsured (hazard ratio [HR], 0.51, 95% CI, 0.41 to 0.63, P < .001). HPV-negative patients with private insurance have improved overall survival compared with HPV-negative patients who were uninsured (HR, 0.62, 95% CI, 0.53 to 0.73, P < .001). HPV-positive patients living in the south had improved overall survival compared with HPV-positive patients living in the west (HR, 0.83, 95% CI, 0.72 to 0.96, P = .013). As assessed through interaction, relationships between survival and insurance (P = .004), rural-urban status (P = .009), and facility location (P = .021) statistically differed between HPV-positive and HPV-negative patients. CONCLUSION: HPV status impact on overall survival for patients with OPSCC is influenced by socioeconomic factors including insurance status and treatment facility. A deeper understanding of these interactions is needed to improve equity of care for patients with OPSCC.

The Pathological Evolution of Glucose Response Curves During the Progression to Type 1 Diabetes in the TrialNet Pathway to Prevention Study.

OBJECTIVE: Glucose response curves (GRCs) during oral glucose tolerance tests (OGTTs) are predictive of type 1 diabetes. We performed a longitudinal analysis in pancreatic autoantibody-positive individuals to assess 1) characteristic GRC changes during progression to type 1 diabetes and 2) GRC changes in relation to ß-cell function changes and to combined glucose and C-peptide response curve (GCRC) changes. RESEARCH DESIGN AND METHODS: Among antibody-positive individuals with serial OGTTs in the TrialNet Pathway to Prevention study, GRC changes from first to last OGTTs were compared between progressors (n = 298) to type 1 diabetes and nonprogressors (n = 2,216). GRC changes from last OGTT before diagnosis to diagnostic OGTTs were studied in progressors. RESULTS: GRCs changed more frequently from biphasic (two peaks) to monophasic (one peak) GRCs between first and last OGTTs in progressors than in nonprogressors (75.4% vs. 51.0%, respectively; P < 0.001). In contrast, GRCs of progressors changed less frequently from monophasic to biphasic than those of nonprogressors (12.6% vs. 30.6%; P < 0.001). Monotonic (continuous increase) GRCs were present in 47.7% of progressors at diagnosis. The early (30-0 min) C-peptide response decreased in progressors with GRCs changing from biphasic to monophasic between first and last OGTTs (P < 0.001) and from monophasic to monotonic between last and diagnostic OGTTs (P < 0.001). Conversely, the early C-peptide response increased among nonprogressors with GRCs changing from monophasic to biphasic (P < 0.001). Changes in GRCs were related to changes in GCRCs. CONCLUSIONS: Characteristic GRC changes, biphasic to monophasic to monotonic, occur during the progression to type 1 diabetes. These GRC changes correspond to decreasing ß-cell function.

Exenatide extended release in patients with type 1 diabetes with and without residual insulin production.

AIMS: To test whether a long-acting GLP-1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function. METHODS: We performed a randomized placebo-controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C-peptide. Seventy-nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C-peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug. RESULTS: At week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C-peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased. CONCLUSION: Treatment with exenatide ER may have short-term benefits in some individuals with T1D who are overweight or who have detectable levels of C-peptide, but short-term improvements were not sustained.

Reducing the Pain Behind Opioid Prescribing in Primary Care.

OBJECTIVE: To describe the efficacy of a comprehensive approach aimed at reducing opioid prescribing in an internal medicine resident clinic. DESIGN: Retrospective observational study. SETTING: Internal medicine primary care resident clinic at a large urban academic medical center. SUBJECTS: All patients receiving opioid prescriptions from the primary care clinic. METHODS: We reviewed pharmacy dispensing data for two hospital-affiliated pharmacies for resident primary care patients filling opioid prescriptions between July 2016 and July 2018. We instituted a comprehensive set of interventions that included resident education, limiting supervision of encounters for long-term opioid therapy (LTOT) to a fixed set of faculty champions, and providing alternate modalities for pain control. We calculated the change in number of opioid prescriptions dispensed, number of patients receiving opioid prescriptions, morphine milligram equivalents (MMEs) dispensed, and average per-patient daily MMEs dispensed. RESULTS: We observed an average monthly reduction of 2.44% (P < 0.001) in the number of prescriptions dispensed and a 1.83% (P < 0.001) monthly reduction in the number of patients receiving prescriptions. Over the two-year period, there was a 74.3% reduction in total MMEs prescribed and a 66.5% reduction in the average MMEs prescribed per patient. CONCLUSIONS: Our findings demonstrate a significant reduction in opioid prescribing after implementation of a comprehensive initiative. Although our study was observational in nature, we witnessed a nearly threefold decrease in opioid prescribing compared with national trends. Our results offer important insights for other primary care resident clinics hoping to engender safe prescribing practices and curb high-dose opioid prescribing.

Weight status and obesity-related dietary behaviours among culturally and linguistically diverse (CALD) children in Victoria, Australia.

BACKGROUND: In developed economies, obesity prevalence is high within children from some culturally and linguistically diverse (CALD) backgrounds. This study aims to identify whether CALD groups in Victoria, Australia, are at increased risk of childhood overweight and obesity, and obesity-related dietary behaviours; compared to their non-CALD counterparts. METHODS: Objective anthropometric and self-report dietary behavioural data were collected from 2407 Grade 4 and 6 primary school children (aged 9-12 years). Children were categorised into CALD and non-CALD cultural groups according to the Australian Standard Classification of Languages. Overweight/obesity was defined according to the World Health Organization growth reference standards. Obesity-related dietary behaviour categories included excess consumption of takeaway foods, energy-dense, nutrient-poor snacks and sugar sweetened beverages. T-tests and chi-square tests were performed to identify differences in weight status and dietary behaviours between CALD and non-CALD children. Logistic regression analyses examined the relationship between CALD background, weight status and dietary behaviours. RESULTS: Middle-Eastern children had a higher overweight/obesity prevalence (53.0%) than non-CALD children (36.7%; p < 0.001). A higher proportion of Middle-Eastern children had excess consumption of takeaway foods (54.9%), energy-dense, nutrient-poor snacks (36.6%) and sugar sweetened beverages (35.4%) compared to non-CALD children (40.4, 27.0 and 25.0%, respectively; p < 0.05). Southeast Asian and African children were 1.58 (95% CI = [1.06, 2.35]) and 1.61 (95% CI = [1.17, 2.21]) times more likely, respectively, to consume takeaway foods at least once per week than non-CALD children. CONCLUSIONS: Disparities in overweight/obesity prevalence and obesity-related dietary behaviours among children in Victoria suggest the need for cultural-specific, tailored prevention and intervention strategies.

An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.

BACKGROUND: Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed. METHODS: We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals. RESULTS: A total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed. CONCLUSIONS: Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).

Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data.

A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved ß-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test-stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved ß-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.