Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults.

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score >3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.

Feasibility of Medical Student Mentors to Improve Transition in Sickle Cell Disease.

OBJECTIVE: Advances in medical care have resulted in nearly 95% of all children with sickle cell disease (SCD) living to adulthood. There is a lack of effective transition programming, contributing to high rates of mortality and morbidity among adolescents and young adults (AYAs) during the transition from pediatric to adult healthcare. This nonrandomized study evaluated the feasibility, acceptability, and preliminary outcomes of a novel medical student mentor intervention to improve transition outcomes for AYA with SCD. METHODS: Eligible participants were ages 18-25 years, either preparing for transition or had transferred to adult care within the past year. Twenty-four AYA with SCD (Mage = 20.3, SD = 2.6) enrolled in the program and were matched with a medical student mentor. Feasibility and acceptability of the intervention was assessed through enrollment rates, reasons for refusal, retention rates, engagement with the intervention, satisfaction, and reasons for drop-out. Dependent t-tests were used to evaluate the preliminary effects of the intervention on patient transition readiness, health-related quality of life, self-efficacy, SCD knowledge, medication adherence, and health literacy. RESULTS: Participants (N = 24) demonstrated adequate retention (75.0%), adherence to the intervention (M = 5.3 of 6 sessions), and satisfaction with the intervention components. Participants demonstrated significant improvements in transition readiness (p = .001), self-efficacy (p = .002), medication adherence (p = .02), and health literacy (p = .05). CONCLUSIONS: A medical student mentor intervention to facilitate transition from pediatric to adult care for AYA with SCD is both feasible and acceptable to patients and medical students. Preliminary results suggest benefits for patients, warranting a larger efficacy study.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma: A report from the International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH).

BACKGROUND: The International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH) seeks to provide a universally acceptable definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma. PROCEDURE: A comprehensive literature search was performed using PubMed and Google Scholar with the search terms "Hodgkin lymphoma," "osseous lesions," "bony involvement," and "pediatric." Publications reviewed included case reports, retrospective analyses, and literature reviews. Each was evaluated for study design, number of participants, median age and age range at diagnosis, percentage of pediatric patients, criteria of interest definition, diagnostic tools, study objectives, and level of evidence. The final definition was based on the available data and consensus of the SEARCH working group. RESULTS: Twenty-five papers specifically addressing cortical bone involvement in Hodgkin lymphoma met the inclusion criteria. Eighteen papers were case reports with literature reviews; the remainder were observational cohort studies. Of these, 14 included pediatric patients (aged 0-21 years). The criteria for cortical bone involvement were not clearly defined in any paper, often varied within a study, and were inconsistent between publications. CONCLUSIONS: The SEARCH group for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (CAYAHL) proposes the following criteria as defining cortical bone involvement: any cortical bone biopsy-proven lesion; a positive bony window lesion on computer tomography (CT), with an FDG-PET positive correlate in a patient with biopsy-proven Hodgkin lymphoma, if there is no other typical skeletal pathology; auspicious skeletal lesions on FDG-PET or magnetic resonance imaging should be confirmed by CT or Tc-99m scan to distinguish cortical lesions from bone marrow involvement. Nodal masses that extend into bone with bony destruction are considered extranodal extension or "E" lesions and do not represent metastatic or stage IV disease.

Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1-2 trial.

BACKGROUND: Patients with primary refractory Hodgkin's lymphoma or early relapse have a poor prognosis. Although many salvage regimens have been developed, there is no standard of care. Brentuximab vedotin and gemcitabine have been shown to be active in patients with relapsed or refractory Hodgkin's lymphoma when used as monotherapy, and each has been successfully used in combination with other agents. Preclinical data suggest that brentuximab vedotin can sensitise lymphoma cells to gemcitabine, supporting the use of the combination. We aimed to define the safety and efficacy of brentuximab vedotin with gemcitabine in children and young adults with primary refractory Hodgkin's lymphoma or early relapse. METHODS: In this Children's Oncology Group, multicentre, single-arm, phase 1-2 trial, we recruited patients with Hodgkin's lymphoma from hospitals across the USA and Canada. Eligible patients were aged younger than 30 years, had no previous brentuximab vedotin exposure, and had primary refractory disease or relapse of less than 1 year from completion of initial treatment. Each 21-day cycle consisted of 1000 mg/m2 intravenous gemcitabine on days 1 and 8 and intravenous brentuximab vedotin on day 1 at 1·4 mg/kg or 1·8 mg/kg. The primary objectives were to establish the recommended phase 2 dose of brentuximab vedotin in this combination, the safety of the combination, and the proportion of patients who achieved a complete response among those treated at the recommended phase 2 level, within four cycles of treatment. This trial is registered with ClinicalTrials.gov, number NCT01780662. FINDINGS: Between Feb 5, 2013, and Aug 19, 2016, 46 patients were enrolled, including one who was found to be ineligible, in the two phases of the study. The recommended phase 2 dose of brentuximab vedotin was 1·8 mg/kg in combination with gemcitabine 1000 mg/m2. 24 (57%) of 42 evaluable patients (95% CI 41-72) given this dose level had a complete response within the first four cycles of treatment. Four (31%) of 13 patients with a partial response or stable disease had all target lesions with Deauville scores of 3 or less after cycle 4. By modern response criteria, these were also complete responses (total number with complete response 28 [67%] of 42 [95% CI 51-80]). The most common grade 3-4 adverse events in all 42 participants treated at the recommended phase 2 dose were neutropenia (15 [36%]), rash (15 [36%]), transaminitis (9 [21%]), and pruritus (4 [10%]). There were no treatment-related deaths. INTERPRETATION: Brentuximab vedotin with gemcitabine is a safe combination treatment with a tolerable toxicity profile for patients with primary refractory Hodgkin's lymphoma or high-risk relapse. The preliminary activity of this combination shown in this trial warrants further investigation in randomised controlled trials. FUNDING: National Institutes of Health and the St. Baldrick's Foundation.

Significance of pleural effusion at diagnosis in pediatric Hodgkin lymphoma: a report from Children's Oncology Group protocol AHOD0031.

BACKGROUND: Pleural effusion at presentation in Hodgkin lymphoma has been associated with inferior outcome but has not been systematically evaluated. OBJECTIVE: To determine whether pleural effusion at presentation in children with Hodgkin lymphoma is a primary indicator of poor prognosis or secondary to associated factors. MATERIALS AND METHODS: Children's Oncology Group (COG) AHOD0031, a randomized, response-based, centrally reviewed protocol, enrolled 1,712 eligible patients <22 years of age with initial presentation of intermediate risk, biopsy-proven Hodgkin lymphoma; 1,423 had available imaging for retrospective review. We coded effusions as fluid-only or with associated pleural nodule or adjacent lung or bone involvement and correlated this with disease stage, tumor response, large mediastinal adenopathy, and mass effect on the superior vena cava (SVC) and left innominate vein. We recorded change in size and character of effusions post-chemotherapy. RESULTS: Pleural effusions were present in 217, with 204 having fluid-only and 13 having associated solid components. Patients with effusions were more likely to have large mediastinal adenopathy (P<0.0001), be slow early responders (P<0.0001) and have higher relapse rate (P<0.0001). Vascular compression was not significantly correlated with pleural effusion. Of 121 patients with adequate [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT imaging, no FDG PET avidity was seen in any pleural effusion but was present in solid components. The side of the pleural effusion in those with moderate or large effusions was highly associated with the side of large mediastinal adenopathy (P<0.0001). Statistical analysis indicates that pleural effusion is an independent risk factor for poorer response and relapse. CONCLUSION: Pleural effusion in Hodgkin lymphoma is an important independent poor prognostic indicator for response and relapse.

Staging Evaluation and Response Criteria Harmonization (SEARCH) for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (CAYAHL): Methodology statement.

International harmonization of staging evaluation and response criteria is needed for childhood, adolescence, and young adulthood Hodgkin lymphoma. Two Hodgkin lymphoma protocols from cooperative trials in Europe and North America were compared for areas in need of harmonization, and an evidence-based approach is currently underway to harmonize staging and response evaluations with a goal to enhance comparisons, expedite identification of effective therapies, and aid in the approval process for new agents by regulatory agencies.

A Stroke Mimic: Methotrexate-induced Neurotoxicity in the Emergency Department.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. The treatment of ALL involves multimodality therapy, and methotrexate (MTX) remains a mainstay of treatment. A complication of MTX therapy includes acute, subacute, and chronic neurotoxocity. Signs and symptoms may range from headaches, dizziness, and mood disorders to seizures and stroke-like symptoms. CASE REPORT: An 18-year-old woman with a history of ALL presented to the emergency department with acute onset of right-sided facial paralysis, right upper extremity flaccid paralysis, and right lower extremity weakness after receiving MTX therapy 3 days earlier. Diagnostic studies were unremarkable and the patient was treated with oral dextromethorphan for presumed MTX-induced neurotoxicity. The patient's symptoms began to improve within hours and she was discharged home within 48 hours with no neurologic deficits. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of this complication of MTX therapy given the sensitivity in regards to time with respect to cerebral vascular accidents. An awareness of this complication in the setting of the appropriate history and physical examination can lead to an accurate diagnosis and intervention and the avoidance of administering thrombolytics.

Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia.

BACKGROUND: Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase. PATIENTS AND METHODS: Between 2012 and 2013, 30 patients (age 1-17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥ 0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥ 0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities. RESULTS: Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥ 0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63-95%) 48 hr post-dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22-66%) 72 hr post-dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%. CONCLUSIONS: IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (≥ 0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated.

A phase 2 study of bortezomib in combination with ifosfamide/vinorelbine in paediatric patients and young adults with refractory/recurrent Hodgkin lymphoma: a Children's Oncology Group study.

A Children's Oncology Group clinical trial aimed to determine if bortezomib (B) increased the efficacy of ifosfamide and vinorelbine (IV) in paediatric Hodgkin lymphoma (HL). This study enrolled 26 relapsed HL patients (<30 years) treated with two to four cycles of IVB. The primary endpoint was anatomic complete response (CR) after two cycles. Secondary endpoints included overall response (OR: CR + partial response) at study completion compared to historical controls [72%; 95% confidence interval (CI): 59-83%]. Although few patients achieved the primary objective, OR with IVB improved to 83% (95% CI: 61-95%; p = 0.32). Although not statistically different, results suggest IVB may be a promising combination.

Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer.

Germline von Hippel-Lindau (VHL) gene mutations underlie dominantly inherited familial VHL tumor syndrome comprising a predisposition for renal cell carcinoma, pheochromocytoma/paraganglioma, cerebral hemangioblastoma, and endolymphatic sac tumors. However, recessively inherited congenital polycythemia, exemplified by Chuvash polycythemia, has been associated with 2 separate 3' VHL gene mutations in exon 3. It was proposed that different positions of loss-of-function VHL mutations are associated with VHL syndrome cancer predisposition and only C-terminal domain-encoding VHL mutations would cause polycythemia. However, now we describe a new homozygous VHL exon 2 mutation of the VHL gene:(c.413C>T):P138L, which is associated in the affected homozygote with congenital polycythemia but not in her, or her-heterozygous relatives, with cancer or other VHL syndrome tumors. We show that VHL(P138L) has perturbed interaction with hypoxia-inducible transcription factor (HIF)1α. Further, VHL(P138L) protein has decreased stability in vitro. Similarly to what was reported in Chuvash polycythemia and some other instances of HIFs upregulation, VHL(P138L) erythroid progenitors are hypersensitive to erythropoietin. Interestingly, the level of RUNX1/AML1 and NF-E2 transcripts that are specifically upregulated in acquired polycythemia vera were also upregulated in VHL(P138L) granulocytes.

Stratification of treatment intensity in relapsed pediatric Hodgkin lymphoma.

Risk-adapted, response-based therapies for pediatric Hodgkin lymphoma have resulted in 5-year survival exceeding 90%. Although high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) are considered standard for most patients with relapsed or refractory Hodgkin lymphoma, a subset of children with low risk relapse do not require AHSCT for cure. Currently there are no widely accepted criteria defining who should receive standard dose chemotherapy and/or radiotherapy, nor is there a standardized treatment regimen. We propose a risk-stratified, response-based algorithm for children with relapsed or refractory Hodgkin lymphoma that is based on a critical appraisal of published outcomes and prognostic factors.

Voxelotor Treatment Providing Transfusion Independence for Patient With Combined Sickle Cell Disease and Lipopolysaccharide-Responsive and Beige-Like Anchor (LRBA) Deficiency.

We present a 22-year-old female with transfusion-dependent anemia due to sickle cell disease (SCD) with lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency whose treatment frequency was moderated with voxelotor (Oxbryta®). The patient was transfusion dependent, initially thought to be secondary only to SCD. After the diagnosis of LRBA deficiency, her regimen included abatacept, sirolimus, hydroxyurea, and folic acid, but she still required intermittent transfusion. She was started on voxelotor in January 2020. Since initiation, her baseline hemoglobin level has increased and she is no longer transfusion dependent.

Patient-Reported Experiences in Voxelotor-Treated Children and Adults with Sickle Cell Disease: A Semistructured Interview Study.

Objective: Voxelotor is a first-in-class sickle hemoglobin-polymerization inhibitor that was approved in 2019 by the US Food and Drug Administration for treatment of patients with sickle cell disease (SCD) aged ≥12 years; in 2021, the approval was extended to children with SCD aged 4 to 11 years. Additionally, both the Ministry of Health and Prevention for the United Arab Emirates and the European Commission granted marketing authorization for voxelotor in September 2021 and February 2022, respectively, for treatment of SCD in adults and pediatric patients aged ≥12 years. Thus, additional information on the patient experience with voxelotor would be useful for patients, caregivers, and healthcare professionals alike. The purpose of this study was to conduct semistructured interviews in an effort to understand the experiences and perspectives of voxelotor-treated patients with SCD. Methods: One-time semistructured interviews with adults, adolescents, and children with SCD and their primary caregivers were conducted in the United States. Twenty-three adults and adolescents were recruited across 4 clinical sites, and 10 children-caregiver dyads were recruited from a single site. The interview was designed to elicit patient perspectives on symptomatic changes with voxelotor and the impact of treatment on patients' perceived health-related quality of life. Individual interview transcripts were analyzed using a thematic analytic approach, and concept saturation was assessed in both cohorts. Results: Most patients reported improvements in their SCD symptoms with voxelotor treatment, specifically regarding pain crises, jaundice, and fatigue. Almost all patients experienced improvements in self-reported health-related quality of life with voxelotor treatment. Conclusions: This study provides patient and caregiver perspectives on the symptomatic benefits of voxelotor treatment. These findings not only highlight the benefits of voxelotor treatment in improving symptoms and increasing health-related quality of life across the entire SCD population but also can inform further research on SCD-specific patient-reported outcomes.

Survival of nonseminomatous germ cell tumors in pediatric patients and young adults - A stage group stratified analysis.

INTRODUCTION: Testicular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group. METHODS: Using the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19-30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group. RESULTS: A total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45-7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99-5.21), P=0.053) compared to pediatric and adolescent patients. CONCLUSIONS: Younger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients.

Associations between race and survival in pediatric patients with diffuse large B-cell lymphoma.

BACKGROUND: The purpose of this study was to examine the factors associated with disparities in overall survival (OS) by race in pediatric diffuse large B-cell lymphoma (DLBCL) patients. METHODS: We evaluated clinical features and survival among patients ≤21 years of age diagnosed with stage I-IV DLBCL from 2004 to 2014 from the National Cancer Database (NCDB) using a multivariable Cox proportional hazards model. RESULTS: Among 1386 pediatric patients with DLBCL, 1023 patients met eligibility criteria. In unadjusted analysis, Black patients had a significantly higher overall death rate than White patients (HRBlack vs. White 1.51; 95% CI: 1.02-2.23, p = 0.041). The survival disparity did not remain significant in adjusted analysis, though controlling for covariates had little effect on the magnitude of the disparity (HR 1.46; 95% CI 0.93-2.31, p = 0.103). In adjusted models, presence of B symptoms, receipt of chemotherapy, stage of disease, and Other insurance were significantly associated with OS. Specifically, patients with B symptoms and those with Other insurance were more likely to die than those without B symptoms or private insurance, respectively (HR 1.75; 95% CI 1.22-2.50, p = 0.002) and (HR 2.56; 95% CI, 1.39-4.73, p = 0.0027), patients who did not receive chemotherapy were three times more likely to die than those who received chemotherapy (HR 3.10; CI 1.80-5.35, p < 0.001), and patients who presented with earlier stage disease were less likely to die from their disease than those with stage IV disease (stages I-III HR 0.34, CI 0.18-0.64, p < 0.001; HR 0.50, CI 0.30-0.82, p = 0.006, HR 0.72, CI 0.43-1.13, p = 0.152, respectively). CONCLUSIONS: Our results suggest that racial disparities in survival may be mediated by clinical and treatment parameters.