Publications by authors named "Elysia Alvarez"

31 Publications

A qualitative study of barriers and facilitators to adolescents and young adults' participation in cancer clinical trials: Oncologist and patient perspectives.

Pediatr Blood Cancer 2021 Dec 16:e29479. Epub 2021 Dec 16.

Center for Oncology Hematology Outcomes Research and Training (COHORT), Division of Hematology and Oncology, University of California Davis, Sacramento, California, USA.

Background: Despite efforts to increase participation of adolescents and young adults (AYAs; 15-39 years) in cancer clinical trials (CTs), enrollment remains very low. Even when provided access to CTs, AYAs are less likely to participate than children and older adults. A better understanding of oncologist- and AYA survivor-reported barriers, facilitators, and potential areas for CT enrollment improvement is needed.

Procedures: From December 2019 to August 2020, we conducted 43 semi-structured interviews with oncologists (n = 17) and AYA cancer survivors (n = 26) who were offered and/or participated in CTs at cancer centers in California and Utah. Thematic analyses were used to interpret the findings.

Results: Oncologists identified a lack of available CTs, strict eligibility criteria, lack of awareness of open CTs, and poor communication between pediatric and adult oncologists as major barriers to enrollment. AYA cancer survivors identified financial and psychosocial barriers, and a poor understanding of what a CT means and its potential benefits as barriers to enrollment. Areas for improvement identified by oncologists and AYAs include educational, financial, and psychosocial support to AYAs. Oncologists also emphasized the need to increase CT availability, improve awareness of open CTs, and better communication between both pediatric and adult oncologists and oncologists and AYAs.

Conclusions: For AYAs with cancer, a lack of CT eligibility and physician awareness of open CTs likely factor into their lower CT enrollment. Potential strategies to improve AYA enrollment in CTs require comprehensive collaboration between pediatric and adult institutions, as well as educational, psychosocial, and financial support to AYAs.
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http://dx.doi.org/10.1002/pbc.29479DOI Listing
December 2021

Treatment at Specialized Cancer Centers Is Associated with Improved Survival in Adolescent and Young Adults with Soft Tissue Sarcoma.

J Adolesc Young Adult Oncol 2021 Dec 15. Epub 2021 Dec 15.

Division of Hematology/Oncology, Center for Oncology, Hematology Outcomes Research and Training (COHORT), University of California Davis School of Medicine, Sacramento, California, USA.

Soft tissue sarcomas (STS) are a heterogeneous group of tumors whose management benefits from a multidisciplinary therapeutic approach. Published data suggest that cancer treatment at a specialized cancer center (SCC) can improve survival in other cancers. Therefore, we examined the impact of the location of treatment on survival in children and adolescents and young adults (AYAs) with STS. We performed a population-based analysis of children and AYAs hospitalized within 1 year of diagnosis with first primary STS (2000-2014) using the California Cancer Registry linked with hospitalization data. Patients were categorized based on receiving all inpatient treatments at a SCC versus part/none. Multivariable Cox proportional hazards regression identified factors associated with overall and STS-specific survival by age group. Results are presented as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Of the 1,674 patients with STS, 142 were children (0-14) and 1,532 were AYAs (15-39) and 89.4% and 40.4% received all inpatient treatments at a SCC, respectively. Overall, the 5-year survival was improved for patients who received all inpatient care at a SCC (59.8% vs. those who received part/none, 50.7%). Multivariable regression analysis found that having all treatments at a SCC was associated with better overall survival (HR, 0.79, CI: 0.65-0.95) in AYAs, but not in children. Our findings demonstrate that treatment for STS at a SCC is associated with better survival in AYAs. Eliminating barriers to treatment of AYAs with STS at SCCs could improve survival in this population.
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http://dx.doi.org/10.1089/jayao.2021.0110DOI Listing
December 2021

Initial cancer treatment and survival in children, adolescents, and young adults with Hodgkin lymphoma: A population-based study.

Cancer 2021 Dec 8;127(24):4613-4619. Epub 2021 Sep 8.

Center for Oncology Hematology Outcomes Research and Training and Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, California.

Background: Hodgkin lymphoma (HL) is a treatable tumor affecting children, adolescents and young adults (AYAs; 15-39 years old). Population-based studies report worse survival for non-White children and AYAs but have limited data on individual therapeutic exposures. This study examined overall and HL-specific survival in a population-based cohort of patients while adjusting for sociodemographic factors and treatment.

Methods: Data for 4807 patients younger than 40 years with HL (2007-2017) were obtained from the California Cancer Registry. Individual treatment information was extracted from text fields; chemotherapy regimens were defined by standard approaches for pediatric and adult HL. Multivariable Cox models examined the influence of patient and treatment factors on survival.

Results: At a median follow-up of 4.4 years, 95% of the patients were alive. Chemotherapy differed by age, with 70% of 22- to 39-year-olds and 41% of <22-year-olds receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (P < .001). In multivariable models, older patients (22-39 vs < 21 y; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11-2.10), Black (vs White patients); HR, 1.90; 95% CI, 1.25-2.88), and Hispanic patients (HR, 1.45; 95% CI, 1.06-1.99) experienced worse survival; among those < 21 y, Black race was associated with a 3.3-fold increased risk of death (HR, 3.26; 95% CI, 1.43-7.42).

Conclusions: In children and AYAs with HL, older age and non-White race/ethnicity predicted worse survival after adjustments for treatment data. Further work is needed to identify the biological and nonbiological factors driving disparities in these at-risk populations.
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http://dx.doi.org/10.1002/cncr.33868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665020PMC
December 2021

Prognostic factors, disparity, and equity variables impacting prognosis in bone sarcomas of the hand: SEER database review.

J Surg Oncol 2021 Dec 25;124(8):1515-1522. Epub 2021 Aug 25.

Department of Orthopaedic Surgery, University of California-Davis, Sacramento, California, USA.

Background: Primary sarcomas originating from the bones of hand and wrist are rare but carry a significant burden of morbidity.

Methods: National Cancer Institute's Surveillance, Epidemiology and End Result database from 1975 to 2017 was queried to report incidence and survival data in 237 patients in the United States. Kaplan-Meier and Cox regression were used to determine the prognostic factors affecting survival. χ test was used to assess the correlation.

Results: Incidence of hand and wrist sarcoma was 0.017 per 100 000 persons in 2017 and has not significantly changed since 1975 (p > 0.05). Disease-specific 5-year and 10-year survival for the entire cohort was 90% and 84%, respectively. On multivariate analysis race "others," histology other than "osteosarcoma," "undifferentiated" grade, and size "≥6 cm" were predictors of worse disease-specific survival. Cross-tabulation of race with other significant prognostic factors on univariate analysis revealed a significant correlation of race with every other significant prognostic factor except for grade.

Conclusions: The current study is an analysis of a population-based registry reporting incidence and survival data for patients with sarcoma of hand and wrist. Independent prognostic factors include race, histology, grade, and size. There is a lack of improvement in survival over the last four decades.
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http://dx.doi.org/10.1002/jso.26659DOI Listing
December 2021

Comorbidities and socioeconomic status are predictors of survival in children and young adults with Burkitt lymphoma.

Leuk Lymphoma 2021 11 1;62(11):2804-2807. Epub 2021 Jun 1.

Center for Oncology Hematology Outcomes Research and Training (COHORT) and Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, CA, USA.

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http://dx.doi.org/10.1080/10428194.2021.1932873DOI Listing
November 2021

Impact of location of inpatient cancer care on patients with Ewing sarcoma and osteosarcoma-A population-based study.

Pediatr Blood Cancer 2021 07 15;68(7):e28998. Epub 2021 Mar 15.

Center for Oncology Hematology Outcomes Research and Training and Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, California, USA.

Background: Ewing sarcoma (EWS) and osteosarcoma (OS) require multidisciplinary treatment. Care at specialized cancer centers (SCC: Children's Oncology Group affiliated and/or National Cancer Institute-designated cancer center) has been found to improve outcomes in patients with leukemia, but studies have not considered location of care and outcomes in EWS and OS patients, an ideal group to evaluate given their specialized multidisciplinary treatment needs.

Methods: Patients hospitalized with primary EWS and OS (2000-2014) were identified using the California Cancer Registry linked with hospitalization data. Patients were divided into age groups (0-18, 19-39, ≥40 years), and classified on whether they received all versus part/none of their inpatient treatment at a SCC within 1 year of diagnosis. Multivariable Cox proportional hazards regression identified factors associated with survival.

Results: There were 531 ES and 959 OS patients. Five-year overall survival was better for patients with EWS (all: 63% vs. part/none: 42%) and OS (all: 64% vs. part/none: 47%) who received all of their treatment at a SCC. After adjusting for sociodemographic and clinical factors, receiving all inpatient cancer treatment at a SCC was associated with superior overall survival (EWS HR: 0.49, CI 0.37-0.67; OS HR: 0.78, CI 0.63-0.97).

Conclusion: Our results suggest that treatment for EWS and OS at a SCC is associated with significantly improved survival even after adjustment for known prognostic factors. The superior survival among those treated at SCCs may be due to having greater access to clinical trials and services at SCCs.
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http://dx.doi.org/10.1002/pbc.28998DOI Listing
July 2021

The prognostic significance of anaplasia in childhood rhabdomyosarcoma: A report from the Children's Oncology Group.

Eur J Cancer 2021 01 7;143:127-133. Epub 2020 Dec 7.

Seattle Children's Hospital, Seattle, WA, United States.

Background: Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic features, anaplasia has been suggested as a potential prognostic indicator, but the clinical significance of anaplasia remains unclear.

Methods: Patients enrolled on one of five recent Children's Oncology Group clinical trials for RMS (D9602, n = 357; D9802, n = 80; D9803, n = 462; ARST0331, n = 335; and ARST0531, n = 414) with prospective central pathology review were included in this study. Clinicopathologic variables including demographic information, risk group, histologic subtype, and anaplasia were recorded along with overall survival (OS) and failure-free survival (FFS) with failure defined by recurrence, progression, or death. The log-rank test was used to compare OS and FFS.

Results: Anaplasia was more common in embryonal RMS (27% of all embryonal RMS) than other subtypes of RMS (11% for alveolar RMS, 7% for botryoid RMS, 11% for spindle cell RMS). On multivariate analyses, anaplasia was not an independent prognostic factor in RMS (OS:hazard ratio (HR) = 1.12, p = 0.43; FFS:HR = 1.07, p = 0.56) across all subtypes or within embryonal RMS only (OS:HR = 1.41, p = 0.078; FFS:HR = 1.25, p = 0.16). Among tumors with TP53 mutations, 69% had anaplasia, while only 24% of tumors with anaplasia had a tumoral TP53 mutation.

Conclusions: Anaplasia is not an independent indicator of adverse outcomes in RMS. Emerging information on the prognostic significance of TP53 mutations raises the possibility that anaplasia may be a surrogate marker of TP53 mutations in some cases. Tumoral TP53 mutation status may be investigated as a prognostic indicator in future studies.
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http://dx.doi.org/10.1016/j.ejca.2020.10.018DOI Listing
January 2021

Impact of Dependent Coverage Provision of the Affordable Care Act on Insurance Continuity for Adolescents and Young Adults With Cancer.

JCO Oncol Pract 2021 06 22;17(6):e882-e890. Epub 2020 Oct 22.

Center for Outcomes Research, Children's Hospital of Philadelphia, Philadelphia, PA.

Purpose: The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act (ACA) allowed enrollees to remain on their parents' health insurance until 26 years of age. We compared rates of insurance disenrollment among patients with cancer who were DCP-eligible at age 19 to those who were not eligible at age 19.

Methods: Using OptumLabs Data Warehouse, which contains longitudinal, real-world, de-identified administrative claims for commercial enrollees, we examined patients born between 1982 and 1993 and diagnosed with cancer between 2000 and 2015. In the recent cohort, patients who turned 19 in 2010-2012 (DCP-eligible to stay on parents' insurance) were matched to patients who turned 19 in 2007-2009 (not DCP-eligible when turning 19). In an earlier control cohort, patients who turned 19 between 2004 and 2006 (not DCP-eligible) were matched to patients who turned 19 between 2001 and 2003 (not DCP-eligible). Patients were matched on cancer type, diagnosis date, demographics, and treatment characteristics. The time to loss of coverage was estimated using Cox models. Difference-in-difference between the recent and earlier cohorts was also evaluated.

Results: A total of 2,829 patients who turned 19 years of age in 2010-2012 were matched to patients who turned 19 in 2007-2009. Median time to disenrollment was 26 months for younger patients versus 22 months for older patients (hazard ratio [HR], 0.85; 95% CI, 0.80 to 0.90; = .001). In 8,978 patients who turned 19 between 2001 and 2006, median time to disenrollment was 20 months among both younger and older patients (HR, 0.99; 95% CI, 0.94 to 1.03; = .59). The difference between the recent cohort and the earlier control cohort was a 15% greater reduction in coverage loss ( < .0001), favoring those turning 19 after the DCP went into effect.

Conclusion: In the vulnerable population of adolescent and young adult cancer survivors, the ACA may have lowered the insurance dropout rate.
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http://dx.doi.org/10.1200/OP.20.00330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258053PMC
June 2021

Treatment Complications and Survival Among Children and Young Adults With Acute Lymphoblastic Leukemia.

JCO Oncol Pract 2020 10 11;16(10):e1120-e1133. Epub 2020 Jun 11.

Division of Health Policy and Management, Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, CA.

Purpose: We previously demonstrated lower early mortality for young adults (YAs) with acute lymphoblastic leukemia (ALL) who received induction treatment at specialized cancer centers (SCCs) versus community hospitals. The aim of this study is to determine the impact of inpatient location of treatment throughout therapy on long-term survival, complications, and cost-associations that have not yet been evaluated at the population level.

Methods: Using the California Cancer Registry linked to a hospitalization database, we identified patients, 0-39 years of age, diagnosed with first primary ALL who received inpatient treatment between 1991 and 2014. Patients were classified as receiving all or part or none of their inpatient treatment at an SCC within 3 years of diagnosis. Inverse probability-weighted, multivariable Cox regression models estimated the associations between location of treatment and sociodemographic and clinical factors with survival. We compared 3-year inpatient costs overall and per day by age group and location of care.

Results: Eighty-four percent (0-18 years; n = 4,549) of children and 36% of YAs (19-39 years; n = 683) received all treatment at SCCs. Receiving all treatment at an SCC was associated with superior leukemia-specific (hazard ratio [HR], 0.76; 95% CI, 0.67 to 0.88) and overall survival (HR, 0.87; 95% CI, 0.77 to 0.97) in children and in YAs (HR, 0.71; 95% CI, 0.61 to 0.83; HR, 0.70; 95% CI, 0.62 to 0.80) even after controlling for complications. The cost of inpatient care during the full course of therapy was higher in patients receiving all of their care at SCCs.

Conclusion: Our results demonstrate that inpatient treatment at an SCC throughout therapy is associated with superior survival; therefore, strong consideration should be given to referring these patients to SCCs.
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http://dx.doi.org/10.1200/JOP.19.00572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189609PMC
October 2020

Classic Hodgkin Lymphoma: A Nonclassic Presentation.

J Pediatr Hematol Oncol 2021 04;43(3):114-115

Division of Pediatric Hematology/Oncology, University of California Davis Medical Center, Sacramento, CA.

Hodgkin lymphoma classically presents as lymphadenopathy with contiguous spread with or without associated B symptoms including night sweats, weight loss, and fever. With timely diagnosis and treatment, this is a potentially curable disease. This report describes a unique case of Hodgkin lymphoma that presented with localized back pain without overt evidence of lymph node involvement. This nonclassic presentation offers a diagnostic challenge that emphasizes the importance of keeping a broad differential in an adolescent or young adult patient with lytic bone lesions.
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http://dx.doi.org/10.1097/MPH.0000000000001825DOI Listing
April 2021

Chronic medical conditions and late effects following non-Hodgkin lymphoma in HIV-uninfected and HIV-infected adolescents and young adults: a population-based study.

Br J Haematol 2020 08 20;190(3):371-384. Epub 2020 Feb 20.

Center for Oncology Hematology Outcomes Research and Training (COHORT), Division of Hematology and Oncology, University of California, Davis, School of Medicine, Sacramento, CA, USA.

Little is known about the incidence of late effects following non-Hodgkin lymphoma (NHL) among adolescent and young adult (AYA, 15-39 years) survivors. Using data from the California Cancer Registry linked to hospital discharge, we estimated the cumulative incidence of late effects at 10 years among AYAs diagnosed with NHL during 1996-2012, who survived ≥2 years. Cox proportional-hazards models were used to investigate the influence of sociodemographic and clinical factors on the occurrence of late effects. Of 4392 HIV-uninfected patients, the highest incident diseases were: endocrine (18·5%), cardiovascular (11·7%), and respiratory (5·0%), followed by secondary primary malignancy (SPM, 2·6%), renal and neurologic (2·2%), liver/pancreatic (2·0%), and avascular necrosis (1·2%). Among the 425 HIV-infected survivors, incidence was higher for all late effects, especially over threefold increased risk of SPM, compared to HIV-uninfected patients (8·1% vs. 2·6%). In multivariable models for HIV-uninfected patients, public or no health insurance (vs. private), residence in lower socioeconomic neighbourhoods (vs. higher), and receipt of a haematopoietic stem cell transplant were associated with a greater risk of most late effects. Our findings of substantial incidence of late effects among NHL AYA survivors emphasise the need for longterm follow-up and appropriate survivorship care to reduce morbidity and mortality in this vulnerable population.
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http://dx.doi.org/10.1111/bjh.16539DOI Listing
August 2020

Acute Care Utilization at End of Life in Sickle Cell Disease: Highlighting the Need for a Palliative Approach.

J Palliat Med 2020 01 7;23(1):24-32. Epub 2019 Aug 7.

Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

People with sickle cell disease (SCD) have a life expectancy of <50 years, so understanding their end-of-life care is critical. We aimed to determine where individuals with SCD were dying and their patterns of care in the year preceding death to highlight end-of-life research priorities and possible opportunities for intervention. Using the California SCD Data Collection Program database (containing administrative data, vital records, and Medicaid claims), we examined people with SCD who died between 2006 and 2015 (cases) at age <80 years and examined their hospital and emergency department (ED) utilization in their last year of life. Comparators included living controls with SCD matched 1:1 based on age, analysis year, insurance, and income. We identified 486 people with SCD (cases) who died at a median age of 45 years (SD: 16 years). Most died in the hospital (63%) and ED (15%). In their last year of life, people with SCD were hospitalized for an average of 42 days (SD: 49 days) over five admissions. Inpatient admissions and ED visits were stable throughout the year until the month before death when acute care utilization sharply increased. In their last year of life, cases had more hospitalizations than controls, but similar ED utilization. People with SCD are dying acutely at a young age and most die in the hospital and the ED. Since clinicians caring for people with SCD currently cannot predict which acute events may be life-threatening, a comprehensive palliative approach to people with SCD must extend beyond chronic pain management and psychosocial support to include advance care planning.
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http://dx.doi.org/10.1089/jpm.2018.0649DOI Listing
January 2020

Decreased Early Mortality in Young Adult Patients With Acute Lymphoblastic Leukemia Treated at Specialized Cancer Centers in California.

J Oncol Pract 2019 04 8;15(4):e316-e327. Epub 2019 Mar 8.

1 University of California, Davis, CA.

Purpose: Studies suggest that patients with acute lymphoblastic leukemia (ALL) have superior survival when treated at specialized cancer centers (SCCs). However, the association of early mortality (< 60 days) with location of initial care, sociodemographic factors, and complications has not been evaluated in pediatric and young adult (YA) patients with ALL.

Methods: Using the California Cancer Registry linked to hospitalization data, we identified pediatric and YA patients with ALL who received inpatient leukemia treatment between 1991 and 2014. Patients were classified as receiving all or part/none of their care at an SCC (Children's Oncology Group- or National Cancer Institute-designated cancer center). Propensity scores were created for treatment at an SCC in each age group. Multivariable, inverse probability-weighted Cox proportional hazards regression models identified factors associated with early mortality. Results are presented as hazard ratios (HRs) and 95% CIs.

Results: Among 6,531 newly diagnosed pediatric (≤ 18 years) and YA (19 to 39 years of age) patients with ALL, 1.6% of children and 5.4% of YAs died within 60 days of diagnosis. Most children received all of their care at an SCC (n = 4,752; 85.7%) compared with 35.5% of YAs (n = 1,779). Early mortality rates were lower in pediatric patients and those receiving all care at an SCC (pediatric: all, 1.5%, v part/none, 2.4%; P = .049; YAs: all, 3.2%, v part/none, 6.6%; P = .001). However, in adjusted models, receiving all care at an SCC was associated with significantly lower early mortality in YAs (HR, 0.51; 95% CI, 0.32 to 0.81), but not in pediatric patients (HR, 0.77; 95% CI, 0.47 to 1.25).

Conclusion: YAs with ALL experience significant reductions in early mortality after treatment at SCCs.
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http://dx.doi.org/10.1200/JOP.18.00264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846041PMC
April 2019

Hematopoietic Cell Transplantation in Young Adult Acute Lymphoblastic Leukemia: A United States Population-Level Analysis.

J Adolesc Young Adult Oncol 2019 06 18;8(3):254-261. Epub 2019 Jan 18.

2 Center for Oncology Hematology Outcomes Research and Training (COHORT) and Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, California.

In this population-based evaluation of adolescents and young adults (AYA) acute lymphoblastic leukemia (ALL), we describe patterns of care (POC) and outcomes regarding hematopoietic cell transplantation (HCT) in first complete remission (CR1). Data were abstracted from the 2013 United States Surveillance, Epidemiology, and End Results POC study; newly diagnosed AYA ALL were included. Multivariable logistic regression evaluated associations with HCT in CR1; Cox proportional hazards regression evaluated survival associations. Of 399 AYAs with ALL included, 102 (28.5%) underwent HCT in CR1. High-risk cytogenetics (odds ratio [OR] = 4.86, 95% confidence interval [CI] = 3.02-7.83) and hyper-cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD) induction (OR = 1.84, 95% CI = 1.07-3.16) were associated with HCT in CR1. Two-year cumulative incidence of relapse, relapse-free survival (RFS), and overall survival (OS) of the entire cohort were 28.3% (95% CI = 23.4-33.4), 69.3% (95% CI = 63.6-74.3%), and 84.1% (95% CI = 79.7-87.5), respectively. Two-year RFS was significantly higher in patients receiving CR1 HCT relative to chemotherapy (83.6%, 95% CI = 72.6-90.5% vs. 64.3%, 95% CI = 57.5-70.3), but no difference was seen in 2-year OS (88.9%, 95% CI = 80.8-93.7 vs. 82.5%, 95% CI = 77.2-86.7). Treatment at a nonteaching hospital was independently associated with inferior OS (hazard ratio = 2.15, 95% CI = 1.23-3.76). Although the ALL landscape is changing, these data provide a snapshot of the use and outcomes of HCT for AYA ALL across the United States.
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http://dx.doi.org/10.1089/jayao.2018.0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588119PMC
June 2019

End-of-Life Care Intensity in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: A Population-Level Analysis.

J Clin Oncol 2018 10 5;36(30):3023-3030. Epub 2018 Sep 5.

Emily E. Johnston, Lori Muffly, Olga Saynina, Lee M. Sanders, and Lisa J. Chamberlain, Stanford University, Stanford; Elysia Alvarez, University of California Davis, Davis, CA; and Smita Bhatia, University of Alabama at Birmingham, Birmingham, AL.

Purpose: Intensity of end-of-life care receives much attention in oncology because of concerns that high-intensity care is inconsistent with patient goals, leads to worse caregiver outcomes, and is expensive. Little is known about such care in those undergoing allogeneic hematopoietic cell transplantation (HCT), a population at high risk for morbidity and mortality.

Patients And Methods: We conducted a population-based analysis of patients who died between 2000 and 2013, within 1 year of undergoing an inpatient allogeneic HCT using California administrative data. Previously validated markers of intensity were examined and included: hospital death, intensive care unit (ICU) admission, and procedures such as intubation and cardiopulmonary resuscitation at end of life. Multivariable logistic regression models determined clinical and sociodemographic factors associated with: hospital death, a medically intense intervention (ICU admission, cardiopulmonary resuscitation, hemodialysis, intubation), and ≥ two intensity markers.

Results: Of the 2,135 patients in the study population, 377 were pediatric patients (age ≤ 21 years), 461 were young adults (age 22 to 39 years), and 1,297 were adults (age ≥ 40 years). The most common intensity markers were: hospital death (83%), ICU admission (49%), and intubation (45%). Medical intensity varied according to age, underlying diagnosis, and presence of comorbidities at time of HCT. Patients with higher-intensity end-of-life care included patients age 15 to 21 years and 30 to 59 years, patients with acute lymphoblastic leukemia, and those with comorbidities at time of HCT.

Conclusion: Patients dying within 1 year of inpatient allogeneic HCT are receiving medically intense end-of-life care with variations related to age, underlying diagnosis, and presence of comorbidities at time of HCT. Future studies need to determine if these patterns are consistent with patient and family goals.
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http://dx.doi.org/10.1200/JCO.2018.78.0957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324087PMC
October 2018

Does Treatment Setting Matter? Evaluating Resource Utilization for Adolescents Treated in Pediatric vs Adult Cancer Institutions.

J Natl Cancer Inst 2019 03;111(3):224-225

Division of Hematology and Oncology, Center for Oncology Hematology Outcomes Research and Training , University of California Davis School of Medicine, Sacramento, CA.

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http://dx.doi.org/10.1093/jnci/djy123DOI Listing
March 2019

Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study.

Blood Adv 2018 04;2(8):895-903

Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA.

Adolescents and young adults (AYAs, 15-39 years) with acute lymphoblastic leukemia (ALL) represent a heterogeneous population who receive care in pediatric or adult cancer settings. Using the California Cancer Registry, we describe AYA ALL patterns of care and outcomes over the past decade. Sociodemographics, treatment location, and front-line therapies administered to AYAs diagnosed with ALL between 2004 and 2014 were obtained. Cox regression models evaluated associations between ALL setting and regimen and overall survival (OS) and leukemia-specific survival (LSS) for the entire cohort, younger AYA (<25 years), and AYAs treated in the adult cancer setting only. Of 1473 cases, 67.7% were treated in an adult setting; of these, 24.8% received a pediatric ALL regimen and 40.7% were treated at a National Cancer Institute (NCI)-designated center. In multivariable analyses, front-line treatment in a pediatric (vs adult) setting (OS HR = 0.53, 95% confidence interval [CI], 0.37-0.76; LSS HR = 0.51, 95% CI, 0.35-0.74) and at an NCI/Children's Oncology Group (COG) center (OS HR = 0.80, 95% CI, 0.66-0.96; LSS HR = 0.80, 95% CI, 0.65-0.97) were associated with significantly superior survival. Results were similar when analyses were limited to younger AYAs. Outcomes for AYAs treated in an adult setting did not differ following front-line pediatric or adult ALL regimens. Our population-level findings demonstrate that two-thirds of AYAs with newly diagnosed ALL are treated in an adult cancer setting, with the majority receiving care in community settings. Given the potential survival benefits, front-line treatment of AYA ALL at pediatric and/or NCI/COG-designated cancer centers should be considered.
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http://dx.doi.org/10.1182/bloodadvances.2017014944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916002PMC
April 2018

Sociodemographic disparities in the occurrence of medical conditions among adolescent and young adult Hodgkin lymphoma survivors.

Cancer Causes Control 2018 06 13;29(6):551-561. Epub 2018 Apr 13.

Center for Oncology Hematology Outcomes Research and Training (COHORT) and Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, CA, USA.

Purpose: Hodgkin lymphoma (HL) survivors experience high risks of second cancers and cardiovascular disease, but no studies have considered whether the occurrence of these and other medical conditions differ by sociodemographic factors in adolescent and young adult (AYA) survivors.

Methods: Data for 5,085 patients aged 15-39 when diagnosed with HL during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to hospitalization data. We examined the impact of race/ethnicity, neighborhood socioeconomic status (SES), and health insurance on the occurrence of medical conditions (≥ 2 years after diagnosis) and the impact of medical conditions on survival using multivariable Cox proportional hazards regression.

Results: Twenty-six percent of AYAs experienced at least one medical condition and 15% had ≥ 2 medical conditions after treatment for HL. In multivariable analyses, Black HL survivors had a higher likelihood (vs. non-Hispanic Whites) of endocrine [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.05-1.78] and circulatory system diseases (HR = 1.58, CI 1.17-2.14); Hispanics had a higher likelihood of endocrine diseases [HR = 1.24 (1.04-1.48)]. AYAs with public or no insurance (vs. private/military) had higher likelihood of circulatory system diseases, respiratory system diseases, chronic kidney disease/renal failure, liver disease, and endocrine diseases. AYAs residing in low SES neighborhoods (vs. high) had higher likelihood of respiratory system and endocrine diseases. AYAs with these medical conditions or second cancers had an over twofold increased risk of death.

Conclusion: Strategies to improve health care utilization for surveillance and secondary prevention among AYA HL survivors at increased risk of medical conditions may improve outcomes.
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http://dx.doi.org/10.1007/s10552-018-1025-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422023PMC
June 2018

Care at specialized cancer centers among young adults with acute lymphoblastic leukemia in California.

Leuk Lymphoma 2018 10 9;59(10):2482-2484. Epub 2018 Feb 9.

c Center for Oncology Hematology Outcomes Research and Training (COHORT) and Division of Hematology and Oncology , University of California Davis School of Medicine , Sacramento , CA , USA.

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http://dx.doi.org/10.1080/10428194.2018.1427856DOI Listing
October 2018

Inpatient utilization and disparities: The last year of life of adolescent and young adult oncology patients in California.

Cancer 2018 04 2;124(8):1819-1827. Epub 2018 Feb 2.

Center for Health Policy/Center for Primary Care and Outcomes Research, Stanford University, Palo Alto, California.

Background: Studies of adolescent and young adult (AYA) oncology end-of-life care utilization are critical because cancer is the leading cause of nonaccidental AYA death and end-of-life care contributes significantly to health care expenditures. This study was designed to determine the quantity of and disparities in inpatient utilization in the last year of life of AYAs with cancer.

Methods: The California Office of Statewide Health Planning and Development administrative discharge database, linked to death certificates, was used to perform a population-based analysis of cancer patients aged 15 to 39 years who died in 2000-2011. The number of hospital days and the inpatient costs were determined for each patient in the last year of his or her life, as were clinical and sociodemographic factors associated with high inpatient utilization. Admission patterns as death approached were also evaluated.

Results: The 12,883 patients were admitted for 40 days on average in the last year of life, and this cost $151,072 per patient in inpatient costs. As death approached, the admission rates and the percentage of all admissions occurring at nonspecialty centers increased. Five percent of patients used 20% of bed days in the last year (high utilizers). Factors associated with high utilization included younger age (15-30 years), Hispanic ethnicity, non-health maintenance organization insurance, and hematologic malignancies.

Conclusions: AYA oncology decedents were admitted for 40 days in their last year of life. Subgroups with high utilization had distinct sociodemographic and clinical characteristics, and nonspecialty center admissions increased as death approached. This demonstrates the need for palliative care at nonspecialty centers. Future studies need to determine whether these patterns are goal-concurrent, include high utilizers, and monitor the effects of health care reform. Cancer 2018;124:1819-27. © 2018 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891351PMC
April 2018

Disparities in the Intensity of End-of-Life Care for Children With Cancer.

Pediatrics 2017 Oct;140(4)

Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, California; and.

Background: Many adult patients with cancer who know they are dying choose less intense care; additionally, high-intensity care is associated with worse caregiver outcomes. Little is known about intensity of end-of-life care in children with cancer.

Methods: By using the California Office of Statewide Health Planning and Development administrative database, we performed a population-based analysis of patients with cancer aged 0 to 21 who died between 2000 and 2011. Rates of and sociodemographic and clinical factors associated with previously-defined end-of-life intensity indicators were determined. The intensity indicators included an intense medical intervention (cardiopulmonary resuscitation, intubation, ICU admission, or hemodialysis) within 30 days of death, intravenous chemotherapy within 14 days of death, and hospital death.

Results: The 3732 patients were 34% non-Hispanic white, and 41% had hematologic malignancies. The most prevalent intensity indicators were hospital death (63%) and ICU admission (20%). Sixty-five percent had ≥1 intensity indicator, 23% ≥2, and 22% ≥1 intense medical intervention. There was a bimodal association between age and intensity: ages <5 years and 15 to 21 years was associated with intense care. Patients with hematologic malignancies were more likely to have high-intensity end-of-life care, as were patients from underrepresented minorities, those who lived closer to the hospital, those who received care at a nonspecialty center (neither Children's Oncology Group nor National Cancer Institute Designated Cancer Center), and those receiving care after 2008.

Conclusions: Nearly two-thirds of children who died of cancer experienced intense end-of-life care. Further research needs to determine if these rates and disparities are consistent with patient and/or family goals.
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http://dx.doi.org/10.1542/peds.2017-0671DOI Listing
October 2017

The Patient Protection and Affordable Care Act dependent coverage expansion: Disparities in impact among young adult oncology patients.

Cancer 2018 Jan 22;124(1):110-117. Epub 2017 Sep 22.

Division of General Pediatrics, Stanford University School of Medicine, Palo Alto, California.

Background: Private health insurance is associated with improved outcomes in patients with cancer. However, to the authors' knowledge, little is known regarding the impact of the Patient Protection and Affordable Care Act Dependent Coverage Expansion (ACA-DCE), which extended private insurance to young adults (to age 26 years) beginning in 2010, on the insurance status of young adults with cancer.

Methods: The current study was a retrospective, population-based analysis of hospitalized young adult oncology patients (aged 22-30 years) in California during 2006 through 2014 (11,062 patients). Multivariable regression analyses examined factors associated with having private insurance. Results were presented as adjusted odds ratios and 95% confidence intervals. A difference-in-difference analysis examined the influence of the ACA-DCE on insurance coverage by race/ethnicity and federal poverty level.

Results: Multivariable regression demonstrated that patients of black and Hispanic race/ethnicity were less likely to have private insurance before and after the ACA-DCE, compared with white patients. Younger age (22-25 years) was associated with having private insurance after implementation of the ACA-DCE (odds ratio, 1.20; 95% confidence interval, 1.06-1.35). In the difference-in-difference analysis, private insurance increased among white patients aged 22 to 25 years who were living in medium-income (2006-2009: 64.6% vs 2011-2014: 69.1%; P = .003) and high-income (80.4% vs 82%; P = .043) zip codes and among Asians aged 22 to 25 years living in high-income zip codes (73.2 vs 85.7%; P = .022). Private insurance decreased for all Hispanic patients aged 22 to 25 years between the 2 time periods.

Conclusions: The ACA-DCE provision increased insurance coverage, but not among all patients. Private insurance increased for white and Asian patients in higher income neighborhoods, potentially widening social disparities in private insurance coverage among young adults with cancer. Cancer 2018;124:110-7. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30978DOI Listing
January 2018

Case Report: Clinical Variation in Children With Thrombopoietin Receptor (C-MPL) Mutations: Report of 2 Cases.

J Pediatr Hematol Oncol 2018 01;40(1):67-70

Departments of Pediatrics.

Congenital amegakaryocytic thrombocytopenia (CAMT, MIM# 604498) is a rare congenital bone marrow failure syndrome which presents early in life with abnormal bleeding because of thrombocytopenia. Classically, megakaryocytes are decreased to absent in the bone marrow. The development of aplastic anemia early in childhood has led to the recommendation for early stem cell transplantation. Quantitative or loss-of-function mutations in the myeloproliferative leukemia gene (c-mpl), whose gene product functions as the thrombopoietin receptor, have been identified as causative for CAMT. Approximately 100 cases of CAMT are published in the medical literature. We describe 2 cases of CAMT who demonstrate disparate clinical courses, thereby highlighting phenotypic differences and increasing awareness of this clinical entity.
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http://dx.doi.org/10.1097/MPH.0000000000000944DOI Listing
January 2018

End-of-Life Intensity for Adolescents and Young Adults With Cancer: A Californian Population-Based Study That Shows Disparities.

J Oncol Pract 2017 09 22;13(9):e770-e781. Epub 2017 Aug 22.

Stanford University School of Medicine, Palo Alto, CA; and University of Alabama School of Medicine at Birmingham, Birmingham, AL.

Purpose: Cancer is the leading cause of nonaccidental death among adolescents and young adults (AYAs). High-intensity end-of-life care is expensive and may not be consistent with patient goals. However, the intensity of end-of-life care for AYA decedents with cancer-especially the effect of care received at specialty versus nonspecialty centers-remains understudied.

Methods: We conducted a retrospective, population-based analysis with the California administrative discharge database that is linked to death certificates. The cohort included Californians age 15 to 39 years who died between 2000 and 2011 with cancer. Intense end-of-life interventions included readmission, admission to an intensive care unit, intubation in the last month of life, and in-hospital death. Specialty centers were defined as Children's Oncology Group centers and National Cancer Institute-designated comprehensive cancer centers.

Results: Of the 12,938 AYA cancer decedents, 59% received at least one intense end-of-life care intervention, and 30% received two or more. Patients treated at nonspecialty centers were more likely than those at specialty-care centers to receive two or more intense interventions (odds ratio [OR], 1.46; 95% CI, 1.32 to 1.62). Sociodemographic and clinical factors associated with two or more intense interventions included minority race/ethnicity (Black [OR, 1.35, 95% CI, 1.17 to 1.56]; Hispanic [OR, 1.24; 95% CI, 1.12 to 1.36]; non-Hispanic white: reference), younger age (15 to 21 years [OR, 1.36; 95% CI, 1.19 to 1.56; 22 to 29 years [OR,1.26; 95% CI,1.14 to 1.39]; ≥ 30 years: reference), and hematologic malignancies (OR, 1.53; 95% CI, 1.41 to 1.66; solid tumors: reference).

Conclusion: Thirty percent of AYA cancer decedents received two or more high-intensity end-of-life interventions. In addition to sociodemographic and clinical characteristics, hospitalization in a nonspecialty center was associated with high-intensity end-of-life care. Additional research is needed to determine if these disparities are consistent with patient preference.
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http://dx.doi.org/10.1200/JOP.2016.020586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598313PMC
September 2017

Improvement in treatment abandonment in pediatric patients with cancer in Guatemala.

Pediatr Blood Cancer 2017 Oct 19;64(10). Epub 2017 Apr 19.

Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California.

Background: Treatment refusal and abandonment are major causes of treatment failure for children with cancer in low- and middle-income countries (LMICs), like Guatemala. This study identified risk factors for and described the intervention that decreased abandonment.

Methods: This was a retrospective study of Guatemalan children (0-18 years) with cancer treated at the Unidad Nacional de Oncología Pediátrica (UNOP), 2001-2008, using the Pediatric Oncology Network Database. Treatment refusal was a failure to begin treatment and treatment abandonment was a lapse of 4 weeks or longer in treatment. The impact of medicina integral, a multidisciplinary psychosocial intervention team at UNOP was evaluated. Cox proportional hazards analysis identified the effect of demographic and clinical factors on abandonment. Kaplan-Meier analysis estimated the survival.

Results: Of 1,789 patients, 21% refused or abandoned treatment. Abandonment decreased from 27% in 2001 to 7% in 2008 following the implementation of medicina integral. Factors associated with increased risk of refusal and abandonment: greater distance to the centre (P < 0.001), younger age (P = 0.017) and earlier year of diagnosis (P < 0.001). Indigenous race/ethnicity (P = 0.002) was associated with increased risk of abandonment alone. Abandonment correlated with decreased overall survival: 0.57 ± 0.02 (survival ± standard error) for those who completed therapy versus 0.06 ± 0.02 for those who abandoned treatment (P < 0.001) at 8.3 years.

Conclusion: This study identified distance, age, year of diagnosis and indigenous race/ethnicity as risk factors for abandonment. A multidisciplinary intervention reduced abandonment and can be replicated in other LMICs.
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http://dx.doi.org/10.1002/pbc.26560DOI Listing
October 2017

Adolescent and young adult oncology patients: Disparities in access to specialized cancer centers.

Cancer 2017 Jul 27;123(13):2516-2523. Epub 2017 Feb 27.

Division of General Pediatrics, Stanford University School of Medicine, Stanford, California.

Background: Adolescents and young adults (AYAs) ages 15 to 39 years with cancer continue to experience disparate survival outcomes compared with their younger and older counterparts. This may be caused in part by differential access to specialized cancer centers (SCCs), because treatment at SCCs has been associated with improved overall survival. The authors examined social and clinical factors associated with AYA use of SCCs (defined as Children's Oncology Group-designated or National Cancer Institute-designated centers).

Methods: A retrospective, population-based analysis was performed on all hospital admissions of AYA oncology patients in California during 1991 through 2014 (n = 127,250) using the Office of Statewide Health Planning and Development database. Multivariable logistic regression analyses examined the contribution of social and clinical factors on always receiving care from an SCC (vs sometimes or never). Results are presented as adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Over the past 20 years, the percentage of patients always receiving inpatient care at an SCC increased over time (from 27% in 1991 to 43% in 2014). In multivariable regression analyses, AYA patients were less likely to always receive care from an SCC if they had public insurance (OR, 0.64; 95% CI, 0.62-0.66), were uninsured (OR, 0.51; 95% CI, 0.46-0.56), were Hispanic (OR, 0.88; 95% CI, 0.85-0.91), lived > 5 miles from an SCC, or had a diagnosis other than leukemia and central nervous system tumors.

Conclusions: Receiving care at an SCC was influenced by insurance, race/ethnicity, geography, and tumor type. Identifying the barriers associated with decreased SCC use is an important first step toward improving outcomes in AYA oncology patients. Cancer 2017;123:2516-23. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30562DOI Listing
July 2017

Pleomorphic myxoid liposarcoma in an adolescent with Li-Fraumeni syndrome.

Pediatr Surg Int 2017 May 3;33(5):631-635. Epub 2017 Feb 3.

Division of Pediatric Surgery, Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Alway Building M116, MC: 5733, Stanford, CA, 94305, USA.

We present the case of a 15-year-old female with a right perineal mass that was found to be pleomorphic myxoid liposarcoma, a recently recognized, rare subtype of liposarcoma. The patient had a strong family history of malignancy and genetic screening revealed a pathogenic TP53 mutation consistent with Li-Fraumeni syndrome.
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http://dx.doi.org/10.1007/s00383-017-4063-xDOI Listing
May 2017

Pediatric Oncology Discharges With Febrile Neutropenia: Variation in Location of Care.

J Pediatr Hematol Oncol 2017 01;39(1):e1-e7

*Division of Pediatric Hematology and Oncology †Division of General Pediatrics ‡The Center for Policy, Outcomes and Prevention, Stanford University School of Medicine, CA.

We examined the use of Pediatric Cancer Specialty Centers (PCSCs) over time and the length of stay (LOS) in pediatric oncology patients with a diagnosis of febrile neutropenia. PCSCs were defined as Children's Oncology Group and California Children's Services designated centers. We performed a retrospective analysis on all discharges of pediatric (0 to 18) oncology patients with febrile neutropenia in California (1983 to 2011) using the private Office of Statewide Health Planning and Development database. We examined influence of age, sex, race/ethnicity, payer, income, distance, tumor type, and complications on utilization of PCSCs and LOS (SAS 9.2). Analysis of 24,559 pediatric oncology febrile neutropenia discharges showed hospitalizations in PCSCs increasing from 48% in 1983 to 94% in 2011. The adjusted regression analysis showed decreased PCSC utilization for ages 15 to 18, Hispanic patients, and those living >40 miles away. The median PCSC LOS was 9 days compared with 7 days at a non-PCSC (P<0.0001). Discharge from a PCSC was associated with a LOS >8 days after controlling for complications. Inpatient PCSC care for febrile neutropenia in California has increased since 1983. Receiving care at a PCSC is influenced by age, tumor type, ethnicity, geography, and complications.
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http://dx.doi.org/10.1097/MPH.0000000000000716DOI Listing
January 2017

The utility of IgM, CD21, HGAL and LMO2 in the diagnosis of pediatric follicular lymphoma.

Hum Pathol 2015 Apr 29;46(4):629-33. Epub 2015 Jan 29.

Department of Pathology, Stanford University, Stanford, CA 94305. Electronic address:

Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular lymphoma arising in adults. Here, we describe a rare case of pFL that showed morphologic features partially overlapping with progressive transformation of germinal centers and reactive follicular hyperplasia. As typical of pFL, neoplastic B cells within follicles did not express B-cell leukemia/lymphoma 2 (BCL2). However, this case showed additional distinctive abnormal findings, which contributed to the diagnosis: (1) diffuse and uniform staining of immunoglobulin M (IgM) on cells within and outside of follicles, (2) abnormally dim expression of CD21 on follicular dendritic cells, and (3) expression of human germinal center-associated lymphoma (HGAL) and LIM domain only 2 (LMO2) on B cells in interfollicular and follicular areas. This case demonstrates the utility of these abnormal features, which can be seen in adult- or usual-type follicular lymphoma, in the diagnosis of pFL. Further studies are necessary to evaluate the significance of these findings in other cases of pFL.
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http://dx.doi.org/10.1016/j.humpath.2014.12.016DOI Listing
April 2015
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