Publications by authors named "Justine M Kahn"

21 Publications

  • Page 1 of 1

Racial Disparities in Children, Adolescents, and Young Adults with Hodgkin Lymphoma Enrolled in the New York State Medicaid Program.

J Adolesc Young Adult Oncol 2021 Oct 8. Epub 2021 Oct 8.

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

We examined the impact of race/ethnicity and age on survival in a publicly insured cohort of children and adolescent/young adults (AYA; 15-39 years) with Hodgkin lymphoma, adjusting for chemotherapy using linked Medicaid claims. We identified 1231 Medicaid-insured patients <1-39 years diagnosed with classical Hodgkin lymphoma between 2005 and 2015, in the New York State Cancer Registry. Chemotherapy regimens were based on contemporary therapeutic regimens. Cox proportional hazards regression models quantified associations of patient, disease, and treatment variables with overall survival (OS) and disease-specific survival (DSS), and are presented as hazard ratios (HR) with confidence intervals (95% CIs). At median follow-up of 6.6 years,  = 1108 (90%) patients were alive; 5-year OS was 92% in children <15 years. In multivariable models, Black (vs. White) patients had 1.6-fold increased risk of death (HR: 1.58, 95% CI: 1.02-2.46;  = 0.042). Stage III/IV (vs. I/II) was associated with 1.9-fold increased risk of death (HR: 1.86, 95% CI: 1.25-2.78;  = 0.002) and treatment at a non-National Cancer Institute (NCI) affiliate was associated with worse DSS (HR: 2.71, 95% CI: 1.47-4.98;  = 0.001). In this Medicaid-insured cohort of children and AYAs with Hodgkin lymphoma, Black race/ethnicity remained associated with inferior OS in multivariable models adjusted for disease, demographic, and treatment data. Further work is needed to identify dimensions of health care access not mediated by insurance, as findings suggest additional factors are contributing to observed cancer disparities in vulnerable pediatric and AYA populations.
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http://dx.doi.org/10.1089/jayao.2021.0131DOI Listing
October 2021

Patterns of National Cancer Institute-Sponsored Clinical Trial Enrollment in Black Adolescents and Young Adults.

Cancer Med 2021 Sep 30. Epub 2021 Sep 30.

Knight Cancer Institute and Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.

Background: Both adolescent and young adult (AYA) and Black or African American (hereafter referred to as Black) cancer patients are historically under-enrolled in cancer treatment trials (CTT). The purpose of this study was to quantify enrollment of Black AYAs in National Cancer Institute (NCI)-sponsored CTTs overall and by age, sex, and cancer diagnosis during 2000-2015.

Methods: Utilizing data from NCI's Cancer Therapy Evaluation Program and the Surveillance, Epidemiology and End Results (SEER) Program, we assessed CTT enrollment in Black patients with cancer and measured changes in enrollment over time between the study periods 2000-2007 and 2008-2015. Enrollment patterns were compared across age groups (≤14 years [y], 15-19y, 20-29y, 30-39y and 40+ years), sex, and cancer diagnosis.

Results: From 2000 through 2015, <3% of Black AYAs (20-39y) enrolled on CTTs. While AYAs had significantly higher cancer incidence than children, 20.5% fewer Black AYAs enrolled on CTTs. Enrollment was lowest among Black males 20-29y, with a mean of 18 enrolling in CTTs annually. The proportion of AYA enrollees who were Black did not change significantly over time periods (2000-2007 vs 2008-2015).

Conclusions: Few Black AYAs enroll in CTTs each year. Given known benefits of clinical trial participation and the well-documented racial and age-related differences in cancer outcomes, addressing barriers to enrollment in these patients may, in turn, reduce disparities. Targeted interventions aimed at increasing the CTT enrollment of Black cancer patients, particularly young Black men, are urgently needed.

Precis: This study documents that compared with Black children, Black adolescent, and young adult (AYA) patients were less likely to enroll in NCI-sponsored CTTs from 2000 to 2015. Black AYA male enrollment decreased with increasing age, highlighting disparities among this specific population in CTT enrollment.
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http://dx.doi.org/10.1002/cam4.4292DOI Listing
September 2021

Strategies to improve diversity, equity, and inclusion in clinical trials.

Cancer 2021 Sep 8. Epub 2021 Sep 8.

Department of Population Sciences, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.

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http://dx.doi.org/10.1002/cncr.33905DOI Listing
September 2021

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

Cancer 2021 Sep 8. 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
September 2021

Improving Health Equity and Reducing Disparities in Pediatric and Adolescent/Young Adult Oncology: In Support of Clinical Practice Guidelines.

J Natl Compr Canc Netw 2021 06 30;19(6):765-769. Epub 2021 Jun 30.

1Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY.

Despite extraordinary strides in cancer therapy over the past 30 years, racial/ethnic, socioeconomic, and age-related survival disparities persist. Hodgkin lymphoma offers an excellent paradigm to understand these disparities because successful approaches are well established in both the up-front and relapsed treatment settings. The following review, which accompanies the 2021 NCCN Guidelines for Pediatric Hodgkin Lymphoma, suggests that systemic inequities in cancer care disproportionately affect minority and low-income children, adolescents, and young adults, and directly contribute to observed disparities in cancer-related outcomes. It proposes that the first step toward reducing disparities is large-scale dissemination of guidelines, because equity is best achieved when treatment approaches are clear, comprehensive, and standardized across all clinical practice settings.
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http://dx.doi.org/10.6004/jnccn.2021.7048DOI Listing
June 2021

Severe Vincristine-related Neurotoxicity in 5 Patients With Pediatric Acute Lymphoblastic Leukemia Requiring Discontinuation of Vincristine: A Description of Long-term Outcome.

J Pediatr Hematol Oncol 2021 Oct;43(7):e997-e999

Department of Pediatrics, Division of Hematology/Oncology, Brown University and Hasbro Children's Hospital, Providence, RI.

Vincristine, a key agent in the treatment of many pediatric malignancies, causes sensory, motor and autonomic neuropathy. We report the clinical courses of 5 patients who required cessation of vincristine after developing severe neurotoxicity during treatment for acute lymphoblastic leukemia. All 5 patients lost the ability to ambulate and 3 had additional severe neurotoxic side effects including vision loss and vocal cord dysfunction. Although prior literature reports poor outcomes for children in whom vincristine was discontinued during acute lymphoblastic leukemia therapy, all 5 patients described here achieved and have maintained complete continuous remission.
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http://dx.doi.org/10.1097/MPH.0000000000002114DOI Listing
October 2021

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium.

Cancer Discov 2021 Jun 9;11(6):1424-1439. Epub 2021 Feb 9.

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. SIGNIFICANCE: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations...
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http://dx.doi.org/10.1158/2159-8290.CD-20-0564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178162PMC
June 2021

Genetic ancestry and skeletal toxicities among childhood acute lymphoblastic leukemia patients in the DFCI 05-001 cohort.

Blood Adv 2021 01;5(2):451-458

Jacob School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY.

Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) and inferior treatment outcomes relative to non-Hispanic White children. We previously reported that Hispanic children with ALL had lower risk of fracture and osteonecrosis. To unravel the genetic root of such ethnic differences, we genotyped 449 patients from the DFCI 05-001 cohort and analyzed their ancestry. Patients with discordant clinical and genetic ancestral groups were reclassified, and those with unknown ancestry were reassigned on the basis of genetic estimates. Both clinical and genetic ancestries were analyzed in relation to risk of bone toxicities and survival outcomes. Consistent with clinically reported race/ethnicity, genetically defined Hispanic and Black patients had significantly lower risk of fracture (Hispanic: subdistribution hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.22-0.81; P = .01; Black: SHR, 0.28; 95% CI, 0.10-0.75; P = .01), and osteonecrosis (Hispanic: SHR, 0.12; 95% CI, 0.02-0.93; P = .04; Black: SHR, 0.24; 95% CI, 0.08-0.78; P = .02). The lower risk was driven by African but not Native American or Asian ancestry. In addition, patients with a higher percentage of Native American ancestry had significantly poorer overall survival and event-free survival. Our study revealed that the lower risk of bone toxicities among Black and Hispanic children treated for ALL was attributed, in part, to the percentage of African ancestry in their genetic admixture. The findings provide suggestive evidence for the protective effects of genetic factors associated with African decent against bone damage caused by ALL treatment and clues for future studies to identify underlying biological mechanisms.
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http://dx.doi.org/10.1182/bloodadvances.2020003060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839368PMC
January 2021

Limitations of Applying the Hematopoietic Cell Transplantation Comorbidity Index in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 01 8;27(1):74.e1-74.e9. Epub 2020 Oct 8.

Department of Pediatrics, Division of Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, New York, New York.

Identifying which patients are at high risk for transplant-related mortality, prior to allogeneic hematopoietic cell transplantation (alloHCT), is crucial both to guide decision making with patients and families and to inform the alloHCT approach. There is a paucity of data evaluating the utility of the HCT comorbidity index (HCT-CI) in pediatric patients. We performed a retrospective cohort study of 188 patients who underwent alloHCT between January 2008 and October 2016 and assessed pretransplant comorbidities defined and weighted by the HCT-CI. The primary endpoint of our study was overall survival (OS). Kaplan-Meier method was used to assess survival estimates at 1-year post-transplant and did not differ based on HCT-CI scores: 78.7% (SE 6.69%) for HCT-CI = 0, 74.7% (SE 6.33%) for HCT-CI = 1 to 2, and 77.3% (SE 4.17%) for HCT-CI ≥3. Multivariable Cox proportional hazards analysis did not show HCT-CI having an effect on OS: hazard ratio (HR) of 0.633 (95% confidence interval [CI], 0.297 to 1.347) for HCT-CI scores 1 to 2 and HR of 0.935 (95% CI, 0.456 to 1.918) for HCT-CI scores ≥3 compared to scores of 0. The most frequent comorbidities observed were hepatic disease (mild in 29%, severe in 23%) and pulmonary disease (moderate in 15% and severe in 29%). However, only 55% were able to complete pulmonary function testing. Hepatic disease was based on transaminitis in 48% and by bilirubin alone in 26% of patients; 46% of patients with hepatic dysfunction had an underlying hemoglobinopathy and hyperbilirubinemia related to ongoing hemolysis. This study evaluates HCT-CI comorbidities in greater detail than has been performed previously in children undergoing alloHCT. We identify challenges with the HCT-CI in the pediatric population and highlight the comorbidities that may benefit from adjustments to their definition to create an improved risk assessment tool for children.
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http://dx.doi.org/10.1016/j.bbmt.2020.10.003DOI Listing
January 2021

Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001.

Pediatr Blood Cancer 2021 01 7;68(1):e28719. Epub 2020 Oct 7.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Background/objectives: While outcomes for pediatric T-cell acute lymphoblastic leukemia (T-ALL) are favorable, there are few widely accepted prognostic factors, limiting the ability to risk stratify therapy.

Design/methods: Dana-Farber Cancer Institute (DFCI) Protocols 05-001 and 11-001 enrolled pediatric patients with newly diagnosed B- or T-ALL from 2005 to 2011 and from 2012 to 2015, respectively. Protocol therapy was nearly identical for patients with T-ALL (N = 123), who were all initially assigned to the high-risk arm. End-induction minimal residual disease (MRD) was assessed by reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS), but was not used to modify postinduction therapy. Early T-cell precursor (ETP) status was determined by flow cytometry. Cases with sufficient diagnostic DNA were retrospectively evaluated by targeted NGS of known genetic drivers of T-ALL, including Notch, PI3K, and Ras pathway genes.

Results: The 5-year event-free survival (EFS) and overall survival (OS) for patients with T-ALL was 81% (95% CI, 73-87%) and 90% (95% CI, 83-94%), respectively. ETP phenotype was associated with failure to achieve complete remission, but not with inferior OS. Low end-induction MRD (<10 ) was associated with superior disease-free survival (DFS). Pathogenic mutations of the PI3K pathway were mutually exclusive of ETP phenotype and were associated with inferior 5-year DFS and OS.

Conclusions: Together, our findings demonstrate that ETP phenotype, end-induction MRD, and PI3K pathway mutation status are prognostically relevant in pediatric T-ALL and should be considered for risk classification in future trials. DFCI Protocols 05-001 and 11-001 are registered at www.clinicaltrials.gov as NCT00165087 and NCT01574274, respectively.
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http://dx.doi.org/10.1002/pbc.28719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369809PMC
January 2021

Race and socioeconomic status in pediatric allogeneic hematopoietic cell transplantation for nonmalignant conditions.

Pediatr Blood Cancer 2020 09 4;67(9):e28367. Epub 2020 Jun 4.

Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, New York.

Background: Survival disparities by race/ethnicity and socioeconomic status (SES) are observed in a wide range of pediatric treatment settings including oncology and solid organ transplantation. To date, few studies have examined the effects of race and SES on outcomes in pediatric allogeneic hematopoietic cell transplantation (HCT). We explored whether survival differed by race/ethnicity or SES in children receiving HCT for nonmalignant conditions at a single institution serving a diverse patient population.

Procedures: The Kaplan-Meier method was used to estimate overall survival (OS) with the log-rank test for between-group comparisons. Cox proportional hazards models were used to identify risk factors for OS, adjusting for treatment- and disease-related factors.

Results: Of 133 subjects, 0 to 21 years, 19% were non-Hispanic (NH) white, 34% were NH black, 40% were Hispanic, and 7% were Asian. Sixty-seven percent of the subjects had public insurance; 49% lived in neighborhoods with poverty rate ≥20%. Primary diagnoses included hemoglobinopathies (56%), bone marrow failure (22%), and other conditions (22%). Median follow-up was 5.8 years (range 0.1-14.5). Analysis revealed no difference in OS by race, insurance type, or neighborhood SES.

Conclusions: Findings from this single-institution study suggest that in pediatric patients undergoing HCT for nonmalignant conditions, treatment at a tertiary care center with a multidisciplinary approach may mitigate drivers of disparities observed in other settings. Additional studies are now needed to further elucidate the complex interrelationships among race, SES, and clinical outcomes for children undergoing HCT.
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http://dx.doi.org/10.1002/pbc.28367DOI Listing
September 2020

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases.

Blood Adv 2020 05;4(9):2084-2094

Division of Hematology/Oncology, College of Medicine, University of Florida, Gainesville, FL.

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.
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http://dx.doi.org/10.1182/bloodadvances.2019000839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218429PMC
May 2020

Survival by Race and Ethnicity in Pediatric and Adolescent Patients With Hodgkin Lymphoma: A Children's Oncology Group Study.

J Clin Oncol 2019 11 20;37(32):3009-3017. Epub 2019 Sep 20.

Emory University School of Medicine, Atlanta, GA.

Purpose: Population-based studies of children and adolescents with Hodgkin lymphoma (HL) report a survival disadvantage in nonwhite-non-Hispanic black (NHB) and Hispanic-patients. Whether disparities persist after adjustment for clinical and treatment-related variables is unknown. We examined survival by race/ethnicity in children receiving risk-based, response-adapted, combined-modality therapy for HL in contemporary Children's Oncology Group trials.

Patients And Methods: This pooled analysis used individual-level data from 1,605 patients (younger than age 1 to 21 years) enrolled in phase III trials for low-risk (AHOD0431), intermediate-risk (AHOD0031), and high-risk (AHOD0831) HL from 2002 to 2012. Event-free survival (EFS) and overall survival (OS) were compared between non-Hispanic white (NHW) and nonwhite patients. Cox proportional hazards for survival were estimated for both de novo and relapsed HL, adjusting for demographics, disease characteristics, and therapy.

Results: At median follow up of 6.9 years, cumulative incidence of relapse was 17%. Unadjusted 5-year EFS and OS were 83% (SE, 1.2%) and 97% (SE, < 1%), respectively. Neither differed by race/ethnicity. In multivariable analyses for OS, nonwhite patients had a 1.88× higher hazard of death (95% CI, 1.1 to 3.3). Five-year postrelapse survival probabilities by race were as follows: NHW, 90%; NHB, 66%; and Hispanic, 80% ( < .01). Compared with NHW, Hispanic and NHB children had 2.7-fold (95% CI, 1.2 to 6.2) and 3.5-fold (95% CI, 1.5 to 8.2) higher hazard of postrelapse mortality, respectively.

Conclusion: In patients who were treated for de novo HL in contemporary Children's Oncology Group trials, EFS did not differ by race/ethnicity; however, adjusted OS was significantly worse in nonwhite patients, a finding driven by increased postrelapse mortality in this population. Additional studies examining treatment and survival disparities after relapse are warranted.
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http://dx.doi.org/10.1200/JCO.19.00812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839907PMC
November 2019

Adolescent and young adult Hodgkin lymphoma: Raising the bar through collaborative science and multidisciplinary care.

Pediatr Blood Cancer 2018 07 30;65(7):e27033. Epub 2018 Mar 30.

Jacobs School of Medicine and Biomedical Sciences, Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo, New York.

Hodgkin lymphoma (HL) is one of the most common cancers in the adolescent and young adult (AYA) population (15-39 years). Despite continued improvements in HL outcomes, AYAs have not exhibited survival gains to the same extent as other age groups. At present, details about tumor biology, optimal therapeutic approaches, supportive care needs, and long-term toxicities in AYAs with HL remain understudied. Herein, we summarize the current state of the AYA population with HL, specifically focusing on how collaborations across the pediatric and medical oncology divide, coupled with multidisciplinary patient care, can further optimize outcomes for this group of patients.
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http://dx.doi.org/10.1002/pbc.27033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980713PMC
July 2018

Adolescent and young adult lymphoma: collaborative efforts toward optimizing care and improving outcomes.

Blood Adv 2017 Oct 10;1(22):1945-1958. Epub 2017 Oct 10.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Lymphomas are responsible for approximately 20% to 25% of annual cancer diagnoses in the adolescent and young adult (AYA) population. In 2006, the National Cancer Institute and the Lance Armstrong Foundation developed a joint Adolescent and Young Adult Oncology Progress Review Group (AYAO-PRG) to formally address the unique cancer burden of patients age 15 to 39 years. As part of their recommendations, the AYAO-PRG identified 5 imperatives for improving outcomes of AYAs with cancer. Broadly, the recommended areas of focus included research, awareness and education, investigational infrastructure, care delivery, and advocacy. In response to the challenges highlighted by the AYAO-PRG, the Lymphoma Research Foundation held the first AYA Lymphoma Research Foundation Symposium on 2 October 2015. At this symposium, clinicians and basic scientists from both pediatric and adult disciplines gave presentations describing the state of the science and proposed a collaborative research agenda built on the imperatives proposed by the AYAO-PRG. The following review presents an in-depth discussion of lymphoma management across pediatric and adult oncologic disciplines, focusing on Hodgkin lymphoma, mature B-cell lymphomas, and anaplastic large cell lymphoma.
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http://dx.doi.org/10.1182/bloodadvances.2017008748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728148PMC
October 2017

An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001.

Pediatr Blood Cancer 2018 03 1;65(3). Epub 2017 Nov 1.

Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, New York, New York.

Purpose: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001.

Patients And Methods: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL.

Results: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome.

Conclusion: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.
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http://dx.doi.org/10.1002/pbc.26871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766393PMC
March 2018

Bone Marrow Harvest in Pediatric Sibling Donors: Role of Granulocyte Colony-Stimulating Factor Priming and CD34 Cell Dose.

Biol Blood Marrow Transplant 2018 02 23;24(2):324-329. Epub 2017 Oct 23.

Department of Pediatrics, Columbia University, New York, New York. Electronic address:

To ensure optimal clinical outcomes for patients while retaining adequate protection for donors, the National Marrow Donor Program developed guidelines specifying that up to 20 mL/kg of bone marrow can be harvested from donors. These guidelines, originally developed for unrelated adult donors, are followed in children as well. We studied the impact of granulocyte colony-stimulating factor (G-CSF) priming on the cellular composition of harvested bone marrow, sought to develop an algorithm to optimize bone marrow harvest volume from pediatric matched sibling donors, and studied the impact of CD34 cell dose on clinical outcomes. We analyzed data from 92 bone marrow harvests and clinical outcomes for 69 sibling recipient-donor duos, The mean age of recipients was 9.85 ± 5.90 years, and that of donors was 11.85 ± 6.36 years. G-CSF priming was not associated with higher yield of CD34 cells/µL. The median CD34 cell count obtained from donors was 700 cells/µL (range, 400-1700 cells/µL) in donors age <6 years, 360 cells/µL (range, 100-1100 cells/µL) in donors age 6 to 12 years, and 300 cells/µL (range, 80-800 cells/µL) in donors age >12 years (P < .001). The number of CD34 cells infused had no impact on traditional clinical outcomes; however, it was significantly related to graft-versus-host disease/relapse/rejection-free survival. Our investigation revealed that ultimately, a CD34 cell count of approximately 3 to 5 × 10/kg was a threshold beyond which increasing CD34 cell dose did not impact outcome. In this study, we addressed the broad question of whether harvesting up to 20 mL/kg of bone marrow from a child donor is truly necessary for optimal outcomes in every pediatric case.
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http://dx.doi.org/10.1016/j.bbmt.2017.10.031DOI Listing
February 2018

How Variable Is Our Delivery of Information? Approaches to Patient Education About Oral Chemotherapy in the Pediatric Oncology Clinic.

J Pediatr Health Care 2017 Jan - Feb;31(1):e1-e6. Epub 2016 Jul 25.

In pediatric patients with acute lymphoblastic leukemia, adherence to oral chemotherapy relies largely on a parent's comprehension of the drug's indication and administration guidelines. We assessed how pediatric oncology providers educate families about oral chemotherapy. We conducted a cross-sectional survey of 68 physicians and nurses from 9 institutions in the Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium. The inter-individual approach to patient education is variable and may consist of handouts, treatment calendars, and discussions. The extent of teaching often varies depending on a provider's subjective assessment of a family's needs. Twenty-five percent of providers suggested standardizing patient teaching. When developing educational models, care teams should consider approaches that (a) objectively identify families in need of extensive teaching, (b) designate allotted teaching time by nursing staff during clinic visits, and (c) maintain the variation and dynamism that informs a successful provider-patient relationship.
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http://dx.doi.org/10.1016/j.pedhc.2016.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154954PMC
January 2018

Racial disparities in the survival of American children, adolescents, and young adults with acute lymphoblastic leukemia, acute myelogenous leukemia, and Hodgkin lymphoma.

Cancer 2016 Sep 10;122(17):2723-30. Epub 2016 Jun 10.

Human Oncology & Pathogenesis Program and Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Race-based survival in children and adolescents with hematologic malignancies has been a national challenge for decades. Large-scale investigations of age- and race-based survival trends over time in these patients have not previously been reported. The objective of this study was to investigate whether race- and age-related differences in pediatric and adolescent and young adult (AYA) leukemia and lymphoma survival persist and to what extent these differences have changed over time.

Methods: Using the Surveillance, Epidemiology, and End Results program, this study investigated the outcomes of black and white (1975-2012; n = 27,369) and white and Hispanic (1992-2012; n = 20,574) children (0-14 years old) and AYAs (15-39 years old) with acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and Hodgkin lymphoma (HL). Estimates of 5- and 10-year relative survival were compared over time.

Results: Trends showed a convergence of survival for white and black children with ALL but a divergence in survival for AYA patients. Hispanic children and AYAs both suffered inferior outcomes. Trends for AML revealed persistent survival differences between black and white children and suggested worsening disparities for AYAs. Survival trends in HL revealed sustained survival differences between black and white AYA patients, whereas no differences were found in Hispanic and white patient outcomes for AML or HL.

Conclusions: Although survival for children and AYAs with ALL, AML, and HL has improved over the past 4 decades, differences persist between black, white, and Hispanic children and AYAs; survival disparities between black and white children with ALL have been nearly eliminated. Strategies aimed at identifying causality and reducing disparities are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2723-2730. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992431PMC
September 2016

Risk Factors and Utility of a Risk-Based Algorithm for Monitoring Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections in Pediatric Recipients after Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2016 09 29;22(9):1646-1653. Epub 2016 May 29.

Department of Pediatrics, Columbia University Medical Center, New York, New York. Electronic address:

Infectious complications, particularly viral infections, remain a significant cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). Only a handful of studies in children have analyzed the risks for and impact of viremia on alloHCT-related outcomes. We conducted a retrospective study of 140 pediatric patients undergoing alloHCT to investigate the incidence of and risk factors for cytomegalovirus (CMV), adenovirus (ADV), and Epstein-Barr virus (EBV) viremia and viral disease after alloHCT. Furthermore, we assessed the impact of viremia on days of hospitalization and develop an algorithm for routine monitoring of viremia. Patients were monitored before alloHCT and then weekly for 180 days after alloHCT. Patients were considered to have viremia if CMV were > 600 copies/mL, EBV were > 1000 copies/mL, or ADV were > 1000 copies/mL on 2 consecutive PCRs. The overall incidences of viremia and viral disease in all patients from day 0 to +180 after alloHCT were 41.4% (n = 58) and 17% (n = 24), respectively. The overall survival for patients with viremia and viral disease was significantly lower compared with those without viremia (58% versus 74.2%, P = .03) and viral disease (48.2% versus 71.2%, P = .024). We identified that pretransplantation CMV risk status, pre-alloHCT viremia, and use of alemtuzumab were associated with the risk of post-alloHCT viremia. The average hospitalization days in patients with CMV risk (P = .011), viremia (P = .024), and viral disease (P = .002) were significantly higher. The algorithm developed from our data can potentially reduce viral PCR testing by 50% and is being studied prospectively at our center. Improved preventative treatment strategies for children at risk of viremia after alloHCT are needed.
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http://dx.doi.org/10.1016/j.bbmt.2016.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496767PMC
September 2016

Survival Impact of Early Post-Transplant Toxicities in Pediatric and Adolescent Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Malignant and Nonmalignant Diseases: Recognizing Risks and Optimizing Outcomes.

Biol Blood Marrow Transplant 2016 08 17;22(8):1525-1530. Epub 2016 May 17.

Department of Pediatrics, Columbia University Medical Center, New York, New York. Electronic address:

In pediatric and adolescent patients undergoing allogeneic hematopoietic cell transplantation, treatment-related toxicities remain a clinical challenge. A paucity of data investigates the risks for and survival impact of treatment-related toxicities in this population. Here the authors assess the relative toxicity of myeloablative, reduced-toxicity, and reduced-intensity conditioning regimens; identify patient-related predictors of post-transplant toxicities; and investigate the impact of early post-transplant toxicities on transplant-related mortality (TRM). In this retrospective study, 164 patients (aged 1 to 22 years) underwent allogeneic stem cell transplantation after busulfan-based conditioning for malignant and nonmalignant diseases between 2000 and 2014. The number of grades III to IV toxicities between days 0 and +30 was calculated for each patient. TRM was calculated to 2 years. Median patient age was 9 years, and median number of toxicities was 3 (range, 0 to 17). The 100-person day incidence of post-transplant toxicities in myeloablative conditioning was not different from the incidence in reduced-toxicity conditioning (13.88 versus 13.59, P = .812). Reduced intensity was less toxic than both myeloablative and reduced toxicity (13.75 versus 8.41, P < .001). Age ≥ 12 years (.276 with SE = .138, P = .045) and unrelated donor transplant (.318 with SE = 0.113, P = .005) were risk factors for ≥3 toxicities. Having ≥3 toxicities or a performance score < 90 conferred higher risk of TRM (P = .021). In pediatric and adolescent patients undergoing hematopoietic cell transplantation, reduced-toxicity conditioning was not significantly less toxic than myeloablative conditioning. Additionally, the number of post-transplant toxicities correlated with the risk of mortality. Further investigations to confirm our findings are warranted.
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http://dx.doi.org/10.1016/j.bbmt.2016.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496771PMC
August 2016
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