Publications by authors named "Robert Hayashi"

77 Publications

Treatment of small and medium retinoblastoma tumors with Iris diode laser.

Eur J Ophthalmol 2021 Feb 2:1120672121991390. Epub 2021 Feb 2.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.

Purpose: Differing techniques have been reported for focal laser therapy for patients with small and medium retinoblastoma. We report the technique used at our center; and report the functional and anatomical outcomes for small and medium retinoblastomas treated with focal laser therapy with or without systemic chemotherapy.

Methods: A retrospective case study was conducted including pediatric patients with macular retinoblastoma treated with systemic chemotherapy and laser ablation from July 1990 to July 2015 at Washington University School of Medicine/Saint Louis Children's Hospital.

Results: Fourteen eyes (11 patients) with small and medium retinoblastoma tumors were treated with repetitive indirect laser hyperthermia and seven of those patients were treated with systemic chemotherapy as well. Using the International Retinoblastoma classification, one eye was stage A, 10 eyes were stage B, and three eyes were stage C. The mean follow-up time was 7.7 years. There were no recurrences of tumor in the patients. Final visual acuity outcomes were 20/20 to 20/50 in four eyes, 20/60 to 20/200 in four eyes, and 20/400 or less in six eyes. None of the patients developed metastatic disease.

Conclusions: The evidence for systemic chemotherapy and diode laser therapy is limited to case series and retrospective reviews, but evidence suggests that it is an effective treatment for small and medium sized retinoblastoma tumors involving the macula with the potential for good visual outcomes.
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http://dx.doi.org/10.1177/1120672121991390DOI Listing
February 2021

Considerations in Preparative Regimen Selection to Minimize Rejection in Pediatric Hematopoietic Transplantation in Non-Malignant Diseases.

Authors:
Robert J Hayashi

Front Immunol 2020 19;11:567423. Epub 2020 Oct 19.

Division of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, MO, United States.

The variables that influence the selection of a preparative regimen for a pediatric hematopoietic stem cell transplant procedure encompasses many issues. When one considers this procedure for non-malignant diseases, components in a preparative regimen that were historically developed to reduce malignant tumor burden may be unnecessary. The primary goal of the procedure in this instance becomes engraftment with the establishment of normal hematopoiesis and a normal immune system. Overcoming rejection becomes the primary priority, but pursuit of this goal cannot neglect organ toxicity, or post-transplant morbidity such as graft-versus-host disease or life threatening infections. With the improvements in supportive care, newborn screening techniques for early disease detection, and the expansion of viable donor sources, we have reached a stage where hematopoietic stem cell transplantation can be considered for virtually any patient with a hematopoietic based disease. Advancing preparative regiments that minimize rejection and transplant related toxicity will thus dictate to what extent this medical technology is fully utilized. This mini-review will provide an overview of the origins of conditioning regimens for transplantation and how agents and techniques have evolved to make hematopoietic stem cell transplantation a viable option for children with non-malignant diseases of the hematopoietic system. We will summarize the current state of this facet of the transplant procedure and describe the considerations that come into play in selecting a particular preparative regimen. Decisions within this realm must tailor the treatment to the primary disease condition to ideally achieve an optimal outcome. Finally, we will project forward where advances are needed to overcome the persistent engraftment obstacles that currently limit the utilization of transplantation for haematopoietically based diseases in children.
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http://dx.doi.org/10.3389/fimmu.2020.567423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604384PMC
October 2020

Patient and Parent Decision-Making in the Setting of Chemotherapy-Induced Sensorineural Hearing Loss.

Ear Hear 2020 Nov/Dec;41(6):1684-1691

Washington University School of Medicine, St. Louis, Missouri, USA.

Objectives: Children with malignancies may be exposed to ototoxic therapies resulting in sensorineural hearing loss (SNHL). There is no consensus as to when intervention with amplification is necessary due to a variety of factors such as disease status, speech and language development, perceived difficulty with communication, and limitations of technology to fit these challenging losses. The decision to proceed with amplification after cancer can be difficult for patients and families. The purpose of this study is (1) to understand the decision-making (DM) process of childhood cancer survivors (CCSs) with SNHL and their parents and (2) to identify their decisional needs.

Design: Semi-structured interviews guided by the Ottawa's decision support framework were recorded and transcribed verbatim. Inclusion criteria were CCSs ages 8 to 30 years old with a Chang grade >1b SNHL and off-therapy; parents of this group were also eligible. Patients with active disease were excluded. Prompts inquired of sources of decisional conflict, role in DM, and DM behaviors. Inductive content analysis of the narrative qualitative data was used.

Results: Seven parents of CCSs and 6 CCSs participated. Themes in the CCS group included: (1) making sense of ototoxic SNHL; (2) desiring personalized education and treatment of SNHL; (3) playing an active role in the joint DM process; and (4) accepting hearing aids requires time and effort. The parent group shared the first and last theme with the CCS group and had two unique themes: (1) needing experts to respect the individual's journey to SNHL acceptance and (2) moving past the cancer experience to acceptance. Parents more often framed their DM within the context of already experiencing the trauma of cancer, whereas CCSs did not. One parent said, "You see all the rubble and you've lived through the devastation of the storm, but now you got to figure out what's broken." CCSs expressed bodily concerns regarding amplification, such as discomfort to the ear and difficulty in adjusting to the volume. The following needs were identified: early, re-enforced education regarding late effects risks; open communication among providers, CCSs, and parents; and audiogram result interpretations in patient- and parent-friendly language.

Conclusions: Understanding the DM process from the CCS and parent's perspectives should be considered when providing counseling for hearing amplification in the setting of cancer-related SNHL. Earlier and consistent delivery of late effects education, open communication regarding risk for SNHL, and improved delivery of audiogram results should be targets for meeting unmet needs. These findings should inform the development of decision aids to reduce decisional conflict in this population.
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http://dx.doi.org/10.1097/AUD.0000000000000886DOI Listing
November 2020

Psychological, educational, and social late effects in adolescent survivors of Wilms tumor: A report from the Childhood Cancer Survivor Study.

Psychooncology 2020 Oct 28. Epub 2020 Oct 28.

Neuropsychology Division, Children's National Health System, Washington, District of Columbia, USA.

Objective: To delineate the impact of treatment exposures and chronic health conditions on psychological, educational, and social outcomes in adolescent survivors of Wilms tumor.

Methods: Parent reports from the Childhood Cancer Survivor Study were analyzed for 666 adolescent survivors of Wilms tumor and 698 adolescent siblings. Adjusting for race and household income, survivors were compared to siblings on the Behavior Problems Index and educational outcomes. Multivariable modified Poisson regression estimated relative risks (RR) for therapeutic exposures and chronic health conditions (CTCAE 4.03 graded) among survivors, adjusting for sex, race, income, and age at diagnosis.

Results: Compared to siblings, adolescent survivors of Wilms tumor were more likely to take psychoactive medication (9.4% vs. 5.1%, p < 0.001) and utilize special education services (25.5% vs. 12.6%, p < 0.001) but did not differ significantly in emotional and behavioral problems. Survivors were less likely to be friendless (7.2% vs. 10.1%, p = 0.04) but were more likely to have difficulty getting along with friends (14.5% vs. 7.8%, p < 0.001). Among survivors, use of special education services was associated with abdomen plus chest radiation (RR = 1.98, CI:1.18-3.34). Those with grade 2-4 cardiovascular conditions had higher risk for anxiety/depression (RR = 1.95, CI:1.19-3.19), headstrong behaviors (RR = 1.91, CI:1.26-2.89), and inattention (RR = 1.56, CI:1.02-2.40).

Conclusions: Adolescent survivors of Wilms tumor were similar to siblings with respect to mental health concerns overall but were more likely to require special education. Monitoring of psychosocial and academic problems through adolescence is warranted, especially among those treated with radiation to the abdomen plus chest or with cardiac conditions.
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http://dx.doi.org/10.1002/pon.5584DOI Listing
October 2020

Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia.

J Clin Oncol 2020 10 19;38(28):3282-3293. Epub 2020 Aug 19.

Department of Pediatrics and The Center for Childhood Cancer Research, The Children's Hospital of Philadelphia and The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Purpose: Nelarabine is effective in inducing remission in patients with relapsed and refractory T-cell acute lymphoblastic leukemia (T-ALL) but has not been fully evaluated in those with newly diagnosed disease.

Patients And Methods: From 2007 to 2014, Children's Oncology Group trial AALL0434 (ClinicalTrials.gov identifier: NCT00408005) enrolled 1,562 evaluable patients with T-ALL age 1-31 years who received the augmented Berlin-Frankfurt-Muenster (ABFM) regimen with a 2 × 2 pseudo-factorial randomization to receive escalating-dose methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX) or high-dose MTX (HDMTX) with leucovorin rescue. Intermediate- and high-risk patients were also randomly assigned after induction to receive or not receive six 5-day courses of nelarabine that was incorporated into ABFM. Patients who experienced induction failure were nonrandomly assigned to HDMTX plus nelarabine. Patients with overt CNS disease (CNS3; ≥ 5 WBCs/μL with blasts) received HDMTX and were randomly assigned to receive or not receive nelarabine. All patients, except those with low-risk disease, received cranial irradiation.

Results: The 5-year event-free and overall survival rates were 83.7% ± 1.1% and 89.5% ± 0.9%, respectively. The 5-year disease-free survival (DFS) rates for patients with T-ALL randomly assigned to nelarabine (n = 323) and no nelarabine (n = 336) were 88.2% ± 2.4% and 82.1% ± 2.7%, respectively ( = .029). Differences between DFS in a four-arm comparison were significant ( = .01), with no interactions between the MTX and nelarabine randomizations ( = .41). Patients treated with the best-performing arm, C-MTX plus nelarabine, had a 5-year DFS of 91% (n = 147). Patients who received nelarabine had significantly fewer isolated and combined CNS relapses compared with patients who did not receive nelarabine (1.3% ± 0.63% 6.9% ± 1.4%, respectively; = .0001). Toxicities, including neurotoxicity, were acceptable and similar between all four arms.

Conclusion: The addition of nelarabine to ABFM therapy improved DFS for children and young adults with newly diagnosed T-ALL without increased toxicity.
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http://dx.doi.org/10.1200/JCO.20.00256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526719PMC
October 2020

Clostridioides difficile Infections in Inpatient Pediatric Oncology Patients: A Cohort Study Evaluating Risk Factors and Associated Outcomes.

J Pediatric Infect Dis Soc 2020 Aug 7. Epub 2020 Aug 7.

Division of Pediatric Hematology/Oncology, Washington University School of Medicine, St Louis, Missouri, USA.

Background: Clostridioides difficile infection (CDI) is a significant source of morbidity in pediatric cancer patients. Few reports to date have evaluated risk factors and short-term outcomes for this population.

Methods: We retrospectively evaluated pediatric oncology admissions at St Louis Children's Hospital from 2009 to 2018. All inpatient cases of diagnosed initial CDI were identified. We aimed to investigate the prevalence of CDI and associated risk factors, including coadmission with another patient with CDI, and to evaluate short-term outcomes including length of stay and delays in subsequent scheduled chemotherapy.

Results: Review of 6567 admissions from 952 patients revealed 109 CDI cases (11.4% of patients). Patients with leukemia or lymphoma, compared to those with solid tumors, were more likely to have CDI (odds ratio [OR], 3 [95% CI, 1.4-6.6], and 3 [95% CI, 1.3-6.8], respectively). Autologous hematopoietic stem cell transplant (HSCT) was also a risk factor (OR, 3.5 [95% CI, 1.7-7.4]). Prior antibiotic exposure independently increased the risk for CDI (OR, 3.0 [95% CI, 1.8-4.8]). Concurrent admission with another patient with CDI also significantly increased the risk (OR, 84.7 [95% CI, 10.5-681.8]). In contrast to previous reports, exposure to acid-suppressing medications decreased the risk for CDI (OR, 0.5 [95% CI, .3-.7]). CDI was associated with increased length of stay (mean difference, 8 days [95% CI, 4.6-11.4]) and prolonged delays for subsequent chemotherapy (mean difference, 1.4 days [95% CI, .1-2.7]).

Conclusions: CDI in pediatric oncology patients significantly prolongs hospitalization and delays chemotherapy treatment plans. Interventions to control CDI will improve the care of pediatric oncology patients.
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http://dx.doi.org/10.1093/jpids/piaa090DOI Listing
August 2020

Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 08;18(8):1105-1123

National Comprehensive Cancer Network.

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.
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http://dx.doi.org/10.6004/jnccn.2020.0036DOI Listing
August 2020

Comparison of total body irradiation versus non- total body irradiation containing regimens for de novo acute myeloid leukemia in children.

Haematologica 2020 06 18. Epub 2020 Jun 18.

Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, p<0.0001) but relapse was lower (23% vs. 37%, p<0.0001) compared to non-TBI regimens. Consequently, overall (62% vs. 60%, p=1.00) and leukemia-free survival (55% vs. 52%, p=0.42) did not differ between treatment groups. Grade II-IV acute GVHD was higher with TBI regimens (56% vs. 27%, p<0.0001) but not chronic GVHD. The 3-year incidence of gonadal or growth hormone deficiency was higher with TBI regimens (24% vs. 8%, p<0.001) but there were no differences in late pulmonary, cardiac or renal impairment. In the absence of a survival advantage, the choice of TBI or non-TBI regimen merits careful consideration with the data favoring non-TBI regimens to limit the burden of morbidity associated with endocrine dysfunction.
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http://dx.doi.org/10.3324/haematol.2020.249458DOI Listing
June 2020

Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children's Oncology Group AALL0434.

J Clin Oncol 2020 09 17;38(26):3062-3070. Epub 2020 Jun 17.

Division of Blood and Marrow Transplantation, Children's National Health System, Washington, DC.

Purpose: The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients.

Patients And Methods: The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible.

Results: At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups ( = .29) or by treatment regimen ( = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients.

Conclusion: COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.
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http://dx.doi.org/10.1200/JCO.20.00531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479761PMC
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 Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University, New York, NY.

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

Prevalence of Ototoxicity Following Hematopoietic Stem Cell Transplantation in Pediatric Patients.

Biol Blood Marrow Transplant 2020 01 5;26(1):107-113. Epub 2019 Sep 5.

Siteman Cancer Center, Washington University School of Medicine, St. Louis Children's Hospital, St Louis, Missouri. Electronic address:

The use of hematopoietic stem cell transplantation (HSCT) is increasing for a variety of diseases. Ototoxicity from this procedure has not been extensively studied. A retrospective chart review examined 275 patients from this institution who underwent HSCT between January 1, 2007, and April 30, 2017. Data extracted included therapy before HSCT and the subsequent course of transplantation. Evaluable patients had complete medical records and interpretable audiograms available. Ototoxicity constituted significant threshold changes from baseline or changes in International Society of Pediatric Oncology/Boston Ototoxicity Grading Scale (SIOP) grade comparing audiogram results just before HSCT with those following the transplantation procedure. A total of 147 patients were evaluable. Ototoxicity was observed in 10.2% of the patients. Higher SIOP grade before HSCT was significantly associated with a higher risk of post-transplantation ototoxicity (P < .01). Previous cisplatin treatment (P < .0001), but not carboplatin or radiation treatment, was also associated with ototoxicity. Patients with a solid tumor or brain tumor (P < .0001) and those who received an autologous transplant (P = .0002) were also at increased risk. No post-transplantation event was significantly associated with ototoxicity. Ototoxicity affects a significant percentage of patients undergoing HSCT, and careful monitoring is needed to identify patients impacted by this procedure.
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http://dx.doi.org/10.1016/j.bbmt.2019.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135908PMC
January 2020

Pediatric-Oncology Simulation Training for Resident Education.

BMJ Simul Technol Enhanc Learn 2019 Jul 7;5(3):155-160. Epub 2018 Sep 7.

Professor of Anesthesiology and Pediatrics, Departments of Anesthesiology and Pediatrics, Washington University School of Medicine, and medical director of the Saigh Pediatric Simulation Center at St. Louis Children's Hospital, St. Louis, Missouri, USA.

Introduction: We sought to evaluate pediatric oncology simulations intended to improve pediatric residents' skills and comfort in caring for children with cancer.

Method: In a non-randomized trial, controls (the first three rotations) received a standard set of lectures, and the intervention arm received these lectures plus five simulation-training scenarios-fever/neutropenia, a new leukemia diagnosis, end-of-life care discussion, tumor lysis syndrome, and a mediastinal mass. All residents were tested after the rotation on the first three scenarios; management skills were evaluated independently by two raters. Before and after training, all residents completed an emotional-appraisal questionnaire evaluating each scenario as a perceived challenge or threat. Analysis of variance (ANOVA) measured differences by study arm in skills-checklist assessments and appraisals; repeated-measures ANOVA measured changes in emotional-appraisal scores.

Results: Forty-two residents (9 control, 33 intervention) participated. Inter-rater agreement for skills-checklist scores using average-measures intraclass correlation was high (0.847), and overall mean scores were significantly higher for the intervention than control group across both raters ( = 0.005). For all residents, perceived challenge increased in the end-of-life simulation, and perceived threat decreased in all three test scenarios. The intervention group, regardless of training year, evaluated the teaching scenarios favorably and felt that challenging oncology situations were addressed, skills were enhanced, and the simulations should be offered to other residents.

Conclusions: It was feasible to introduce residents to difficult pediatric oncology scenarios using simulation. The intervention group performed more skills than controls when tested, and perceive threat declined in all residents after their pediatric oncology rotation.
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http://dx.doi.org/10.1136/bmjstel-2018-000347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724731PMC
July 2019

Scope of hearing loss in Beckwith-Wiedemann syndrome and hemihypertrophy.

Am J Med Genet A 2019 11 24;179(11):2307-2310. Epub 2019 Jul 24.

Washington University in Saint Louis School of Medicine, St. Louis, Missouri.

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http://dx.doi.org/10.1002/ajmg.a.61308DOI Listing
November 2019

Late Health Outcomes After Contemporary Lymphome Malin de Burkitt Therapy for Mature B-Cell Non-Hodgkin Lymphoma: A Report From the Childhood Cancer Survivor Study.

J Clin Oncol 2019 10 8;37(28):2556-2570. Epub 2019 Jul 8.

St Jude Children's Research Hospital, Memphis, TN.

Purpose: The widely used, risk-based Lymphome Malin de Burkitt (LMB) chemotherapy regimen has improved survival rates for children with mature B-cell non-Hodgkin lymphoma (NHL); however, associated late effects remain understudied. We assessed late health outcomes after LMB treatment in the Childhood Cancer Survivor Study.

Patients And Methods: Multivariable regression models compared chronic health conditions, health status, and socioeconomic and neurocognitive outcomes between survivors of NHL treated with the LMB regimen (n = 126), survivors of NHL treated with non-LMB regimens (n = 444), and siblings (n = 1,029).

Results: LMB survivors were a median age of 10.2 years (range, 2.5 to 20.5 years) at diagnosis and 24.0 years (range, 10.3 to 35.3 years) at evaluation. Compared with siblings, LMB survivors were at increased risk for adverse health outcomes. However, survivors of NHL treated with LMB and non-LMB regimens did not differ with regard to risk of having any chronic health conditions, impaired health status, neurocognitive deficits, or poorer socioeconomic outcomes. Increased risk for the following specific neurologic conditions was observed in LMB survivors compared with non-LMB survivors: epilepsy (relative risk [RR], 15.2; 95% CI, 3.1 to 73.4); balance problems (RR, 8.9; 95% CI, 2.3 to 34.8); tremors (RR, 7.5; 95% CI, 1.9 to 29.9); weakness in legs (RR, 8.1; 95% CI, 2.5 to 26.4); severe headaches (RR, 3.2; 95% CI, 1.6 to 6.3); and prolonged arm, leg, or back pain (RR, 4.0; 95% CI, 2.2 to 7.1). The survivors from the group C LMB risk group (n = 50) were at the highest risk for these conditions; however, except for worse functional status (odds ratio, 2.7; 95% CI, 1.2 to 5.8), they were not at increased risk for other adverse health status or socioeconomic outcomes compared with non-LMB survivors.

Conclusion: Survivors treated with LMB and non-LMB regimens are largely comparable in late health outcomes except for excess neurotoxicity among LMB survivors. These data inform treatment efforts seeking to optimize disease control while minimizing toxicity.
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http://dx.doi.org/10.1200/JCO.19.00525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001792PMC
October 2019

Adolescent and young adult cancer survivorship: The new frontier for investigation.

Authors:
Robert J Hayashi

Cancer 2019 06 20;125(12):1976-1978. Epub 2019 Mar 20.

Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis Children's Hospital, St. Louis, Missouri.

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http://dx.doi.org/10.1002/cncr.32064DOI Listing
June 2019

Adolescent survivors' information needs for transitions to postsecondary education and employment.

Pediatr Blood Cancer 2019 04 8;66(4):e27547. Epub 2018 Nov 8.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.

Background: Adolescent and young adult (AYA) survivors of cancer and central nervous system (CNS) tumors endure major life disruptions with their diagnosis, treatment, and the burden of emerging learning difficulties. Survivors and their parents often struggle to obtain more academic support as survivors transition through school. This study explored the knowledge and experience survivors and their parents need as they progress through school to college.

Methods: This cross-sectional study examined childhood cancer and CNS tumor survivors, aged 11 to 21 years, with a known learning difficulty (Individual Education Plan, 504 Plan) and their parents. We assessed participants' knowledge of and experience with transition planning for postsecondary education and independent living.

Results: Ninety-two AYA survivors and parents (45 survivors, 47 parents) completed the survey. High school-aged survivors described their learning difficulties better than middle school-aged survivors. Survivors estimated their abilities higher than did their parents. Despite a majority of survivors expecting to attend college, 68.5% of survivors and 57.9% of parents were not certain how to get special accommodations for standardized college entrance exams. Only 20.8% of survivors were aware of what a transition plan includes. Parents understood the transition planning process and when it should begin better than the students (P = 0.001), but many parents (40.0%) were still unsure.

Conclusions: AYA survivors and parents lack knowledge necessary to successfully transition to their goals after high school. Greater education is needed.
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http://dx.doi.org/10.1002/pbc.27547DOI Listing
April 2019

Asymmetric sensorineural hearing loss is a risk factor for late-onset hearing loss in pediatric cancer survivors following cisplatin treatment.

Pediatr Blood Cancer 2019 01 18;66(1):e27494. Epub 2018 Oct 18.

Division of Pediatric Hematology/Oncology, Department of Pediatrics Washington University School of Medicine, St. Louis, Missouri.

Background: Ototoxicity is a significant complication of cisplatin treatment. Hearing loss can be symmetric or asymmetric, and may decline after therapy. This study examined the risks of asymmetric and late-onset hearing loss (LOHL) in cisplatin-treated pediatric patients with cancer.

Methods: A retrospective review of 993 patients' medical and audiological charts from August 1990 to March 2015 was conducted using stringent criteria to characterize patients with asymmetric hearing loss (AHL) or LOHL. Audiologic data were reviewed for 248 patients that received cisplatin to assess cisplatin-induced sensorineural hearing loss and its associated risk factors.

Results: Of the patients evaluable for AHL, 26% exhibited this finding. Of those evaluable for LOHL, 42% of the patients' hearing worsened more than 6 months after therapy completion. Radiation and type of cancer diagnosis were major risk factors for both AHL and LOHL. Furthermore, LOHL was linked to age of diagnosis, noncranial radiation, and longer audiologic follow-up. AHL was strongly associated with LOHL-60% of patients with AHL also had LOHL. Logistic regression analysis revealed that patients with AHL (OR 6.3, 95% CI: 2.2-17.8, P = 0.0005) or those receiving radiation (OR 3.2, 95% CI: 1.2-8.6, P = 0.02) were at greatest risk for LOHL.

Conclusion: Children receiving cisplatin therapy are at risk for developing AHL and LOHL. Those that have received radiation and/or with AHL are at increased risk for further hearing decline. Long-term monitoring of these patients is important for early intervention as hearing diminishes.
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http://dx.doi.org/10.1002/pbc.27494DOI Listing
January 2019

Immune Reconstitution and Infection Patterns after Early Alemtuzumab and Reduced Intensity Transplantation for Nonmalignant Disorders in Pediatric Patients.

Biol Blood Marrow Transplant 2019 03 12;25(3):556-561. Epub 2018 Oct 12.

Washington University and Saint Louis Children's Hospital, St. Louis, Missouri. Electronic address:

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many nonmalignant disorders (NMD) and is curative or prevents disease progression. Reduced-intensity conditioning (RIC) in HSCT for NMD may reduce regimen-related acute toxicities and late complications. Myeloablation is often replaced by immune suppression in RIC regimens to support donor engraftment. The pace of immune reconstitution after immune suppression by RIC regimens is influenced by agents used, donor source, and graft-versus-host disease prophylaxis/treatment. In a multicenter trial (NCT 00920972) of HSCT for NMD, a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan was substituted for myeloablation. Alemtuzumab was administered early (days -21 to -19) to mitigate major lymphodepletion of the incoming graft and the risk of graft rejection. Immune reconstitution and infectious complications were prospectively monitored for 1-year post-HSCT. Seventy-one patients met inclusion criteria for this report and received marrow or peripheral blood stem cell transplants. Immune reconstitution and infections are reported for related donor (RD) and unrelated donor (URD) transplants at 3 time-points (100days, 6 months, and 1 year post-HSCT). Natural killer cell recovery was rapid, and numbers normalized in both cohorts by day +100. Mean CD3, CD4, and CD8 T-lymphocyte numbers normalized by 6 months after RD HSCT and by 1 year in the URD group. CD4 and CD8 T-lymphocyte counts were significantly higher in patients who received RD HSCT at 6 months and at 1 year, respectively, post-HSCT compared with patients who received URD HSCT. The pace of CD19 B-cell recovery was markedly different between RD and URD cohorts. Mean B-cell numbers were normal by day 100 after RD HSCT but took 1 year post-HSCT to normalize in the URD cohort. Despite these differences in immune reconstitution, the timing and nature of infections did not differ between the groups, presumably because of comparable T-lymphocyte recovery. Immune reconstitution occurred at a faster pace than in prior reports using RIC with T-cell depletion. The incidence of infections was similar for both cohorts and occurred most frequently in the first 100days post-HSCT. Viral and fungal infections occurred at a lower incidence in this cohort, with "early" alemtuzumab compared with regimens administering serotherapy in the peritransplantation period. Patients were susceptible to bacterial infections primarily in the first 100days irrespective of donor source and had no increase in mortality from the same. The overall mortality rate from infections was 1.4% at 1 year. Close monitoring and prophylaxis against bacterial infections in the first 100days post-HSCT is necessary but is followed by robust immune reconstitution, especially in the T-cell compartment.
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http://dx.doi.org/10.1016/j.bbmt.2018.10.008DOI Listing
March 2019

Outcomes after Second Hematopoietic Cell Transplantation in Children and Young Adults with Relapsed Acute Leukemia.

Biol Blood Marrow Transplant 2019 02 19;25(2):301-306. Epub 2018 Sep 19.

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT.
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http://dx.doi.org/10.1016/j.bbmt.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339844PMC
February 2019

Granulomatous dermatitis secondary to vemurafenib in a child with Langerhans cell histiocytosis.

Pediatr Dermatol 2018 Nov 14;35(6):e402-e403. Epub 2018 Sep 14.

Division of Dermatology, Departments of Medicine and Pediatrics, School of Medicine, Washington University, St. Louis, Missouri.

We present a 3-year-old boy with Langerhans cell histiocytosis who developed granulomatous dermatitis while taking vemurafenib. Vemurafenib currently has Food and Drug Administration approval for the treatment of BRAF V600E+ metastatic melanoma in adults, but recent discoveries of BRAF V600E in more than half of tested Langerhans cell histiocytosis lesions have prompted clinical trials of vemurafenib therapy for children with refractory, multisystem Langerhans cell histiocytosis. This report contributes to the knowledge of its potential side effects when used in children.
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http://dx.doi.org/10.1111/pde.13613DOI Listing
November 2018

Prevalence and nature of hearing loss in a cohort of children with sickle cell disease.

Pediatr Blood Cancer 2019 01 11;66(1):e27457. Epub 2018 Sep 11.

Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.

Background: Sickle cell disease (SCD) may cause injury to any organ, including the auditory system. Although the association of SCD and hearing loss has been described, the nature of this complication is unknown. We sought to establish the prevalence and nature of hearing loss in a referred cohort of children with SCD and to identify correlating disease- or treatment-associated factors.

Procedure: We conducted a retrospective review of patients with SCD < 22 years of age who had hearing evaluations between August 1990 and December 2014. Demographics, audiograms, and disease and treatment variables were analyzed.

Results: Two hundred and ten audiograms among 81 patients were reviewed, and 189 were evaluable. Seventy-two children constituted the referred cohort. Fourteen (19.4%) had hearing loss documented on at least one audiogram. Seven (9.7%) patients had only conductive hearing loss, and the loss persisted for up to 10.3 years. The median age of first identification was eight years. Six (8.3%) patients had hearing loss that was at least partially sensorineural. One patient's hearing loss was ambiguous. All sensorineural hearing losses were unilateral and 4/6 patients had prior documented normal hearing, indicating acquired loss. No correlations were identified.

Conclusions: Both conductive and sensorineural hearing losses are more prevalent in our study population than those observed in the general pediatric population. In children with SCD, sensorineural hearing loss appears to be acquired and unilateral. Conductive hearing loss was identified in older children and can persist. Serial screening is needed for early detection and more prompt intervention in this population.
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http://dx.doi.org/10.1002/pbc.27457DOI Listing
January 2019

Comparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation.

Biol Blood Marrow Transplant 2019 01 25;25(1):73-85. Epub 2018 Aug 25.

Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.
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http://dx.doi.org/10.1016/j.bbmt.2018.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355336PMC
January 2019

Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization.

J Clin Oncol 2018 10 23;36(29):2926-2934. Epub 2018 Aug 23.

Stuart S. Winter, Children's Minnesota Cancer and Blood Disorders Program, Minneapolis, MN; Kimberly P. Dunsmore, Carilion Clinic, Roanoke, VA; Meenakshi Devidas and Zhiguo Chen, University of Florida, Gainesville, FL; Brent L. Wood, Seattle Children's Hospital, Seattle, WA; Natia Esiashvili, Emory University, Atlanta, GA; Nancy Eisenberg, University of New Mexico Health Sciences Center, Albuquerque, NM; Nikki Briegel, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Robert J. Hayashi, St Louis Children's Hospital, St Louis, MO; Julie M. Gastier-Foster, Nationwide Children's Hospital; Julie M. Gastier-Foster and Nyla A. Heerema, Ohio State University, Columbus, OH; Andrew J. Carroll, University of Alabama at Birmingham, Birmingham, AL; Barbara L. Asselin, University of Rochester Medical Center and Wilmot Cancer Institute, Rochester; Elizabeth A. Raetz and William L. Carroll, Perlmutter Cancer Center at NYU Langone Health, New York, NY; Paul S. Gaynon, Children's Hospital of Los Angeles, Los Angeles; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; Michael J. Borowitz, Johns Hopkins University, Baltimore, MD; Karen R. Rabin, Baylor College of Medicine, Houston; Naomi J. Winick, University of Texas Southwestern, Dallas, TX; Patrick A. Zweidler-Mckay, ImmunoGen, Waltham, MA; and Stephen P. Hunger, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.

Purpose: Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children's Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen.

Patients And Methods: COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase. All patients with T-ALL, except for those with low-risk features, received prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation during either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase.

Results: AALL0434 accrued 1,895 patients from 2007 to 2014. The 5-year event-free survival and overall survival rates for all eligible, evaluable patients with T-ALL were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively. The 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia were randomly assigned to receive ABFM with C-MTX (n = 519) or HDMTX (n = 512). The estimated 5-year disease-free survival ( P = .005) and overall survival ( P = .04) rates were 91.5% (95% CI, 88.1% to 94.8%) and 93.7% (95% CI, 90.8% to 96.6%) for C-MTX and 85.3% (95% CI, 81.0%-89.5%) and 89.4% (95% CI, 85.7%-93.2%) for HDMTX. Patients assigned to C-MTX had 32 relapses, six with CNS involvement, whereas those assigned to HDMTX had 59 relapses, 23 with CNS involvement.

Conclusion: AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received CRT, with later timing for those receiving HDMTX.
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http://dx.doi.org/10.1200/JCO.2018.77.7250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366301PMC
October 2018

Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma.

Leuk Res 2018 11 19;74:130-136. Epub 2018 Jul 19.

Department of Oncology, King Faisal Specialist Hospital, Riyadh, Saudi Arabia.

Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.

Results: 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.

Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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http://dx.doi.org/10.1016/j.leukres.2018.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219911PMC
November 2018

Special Therapy and Psychosocial Needs Identified in a Multidisciplinary Cancer Predisposition Syndrome Clinic.

J Pediatr Hematol Oncol 2019 03;41(2):133-136

Departments of Pediatrics, Division of Pediatric Hematology and Oncology.

Identification of patients with cancer predisposition syndromes (CPSs) can provide vital information to guide care of an existing cancer, survey for future malignancy, and counsel families. The same underlying mutation responsible for a CPS may also result in other phenotypic abnormalities amenable to therapeutic intervention. The purpose of this study was to examine patients followed in our multidisciplinary CPS clinic to determine the prevalence and scope of medical and psychosocial needs. Data from a baseline evaluation of a single-center patient registry was reviewed. Eligible patients included those with a known or suspected CPS. Over 3 years, 73 patients consented and had successful follow-up. Utilization rate of special therapies, defined as speech therapy, occupational therapy, and/or physical therapy, in the CPS population was 50.7%, significantly higher than a representative sample of children with special needs. Prevalence of 504/IEP (Individualized Education Program) utilization was 20.5%. Patients with CPSs have a high prevalence of medical and psychosocial needs beyond their risk for cancer, for which early screening for necessary interventions should be offered to maximize the patient's developmental potential. Future research is needed to further define the developmental and cognitive phenotypes of these syndromes, and to evaluate the effectiveness of subsequent interventions.
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http://dx.doi.org/10.1097/MPH.0000000000001251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348029PMC
March 2019

Development of Electronic Chemotherapy Roadmaps for Pediatric Oncology Patients.

J Pediatr Oncol Nurs 2018 Sep/Oct;35(5):314-319. Epub 2018 Apr 10.

2 Washington University School of Medicine, St. Louis, MO, USA.

A chemotherapy roadmap is a summary of the chemotherapy plan for a pediatric oncology patient. Chemotherapy roadmaps exist as paper documents for most, if not all, pediatric oncology programs. Paper chemotherapy roadmaps are associated with risks that can negatively affect the safety of the chemotherapy process. This institution explored the feasibility of converting paper chemotherapy roadmaps into an electronic form. The pediatric information systems team developed an innovative computer application that can generate electronic chemotherapy roadmaps, and the pediatric oncology program established a novel workflow that can operationalize them. Electronic chemotherapy roadmaps have been produced for 36 treatment protocols, and 369 electronic chemotherapy roadmaps have been used for 352 pediatric oncology patients. They have functioned as designed and have not had any unintended effects. In the 5 years after their implementation, the average proportion of patient safety events involving paper or electronic chemotherapy roadmaps decreased by 78.7%. This report is the first to demonstrate the feasibility of creating and implementing electronic chemotherapy roadmaps. Continued expansion of the current library will be necessary to formally test the hypothesis that electronic chemotherapy roadmaps can decrease the risks associated with their paper counterparts and increase the safety of the chemotherapy process.
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http://dx.doi.org/10.1177/1043454218767876DOI Listing
September 2019

Knowledge and perceptions of infertility in female cancer survivors and their parents.

Support Care Cancer 2018 Jul 9;26(7):2433-2439. Epub 2018 Feb 9.

Washington University School of Medicine, 1 Children's Place, St. Louis, MO, 63110, USA.

Purpose: The purpose of this study was to assess knowledge and perceptions of infertility, reproductive concerns, quality of life, and emotional burden of fertility concerns in adolescent female cancer survivors and their parents.

Methods: A cross-sectional design was used to investigate reproductive knowledge and concerns among female childhood cancer survivors and their parents. The instruments administered at a single, routine visit were the 13-item knowledge instrument, Adolescent Fertility Values Clarification Tool (VCT), Impact of Event Scale (IES), and Pediatrics Quality of Life Assessment (PedsQL). The knowledge instrument was given to both patients and caregivers, while the PedsQL and VCT were given to only patients and IES only to caregivers.

Results: Twenty-six survivors and 23 parents completed evaluations. The mean age of survivors was 16. The mean knowledge instrument score for survivors was 9.5 (± 1.9) and 9.96 (± 1.7) for parents with a maximum possible score of 13. The VCT indicated almost all patients agreed or strongly agreed they would like more information on how their treatment may affect their fertility, with 84.6% identified wanting a baby in the future. The mean survivor PedsQL score was 67.7 (± 15.3). While parental IES scores as whole did not endorse symptoms of PTSD, 30% of our sample did fall within the range for PTSD.

Conclusion: Although this population of women has above average knowledge scores, they still demonstrated a desire for more information on reproduction after cancer therapy. While PedsQL scores fell within a normal range, survivors report infertility would cause negative emotions.

Implication For Cancer Survivors: This information can be used refine educational programs within survivorship clinics to improve knowledge of post-treatment reproductive health.
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http://dx.doi.org/10.1007/s00520-018-4080-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982449PMC
July 2018

Determining the prevalence of vestibular screening failures in pediatric cancer patients whose therapies include radiation to the head/neck and platin-based therapies: A pilot study.

Pediatr Blood Cancer 2018 06 30;65(6):e26992. Epub 2018 Jan 30.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.

Background: Sensorineural hearing loss due to ototoxic cancer therapy is well established; effects on the vestibular system are unknown. We examined the feasibility of implementing vestibular screens for pediatric cancer survivors exposed to ototoxic agents. The prevalence of screening failures is reported.

Methods: Cancer survivors who were 6-17 years, at least 1-month posttreatment, and received ototoxic therapy (radiation to the head/neck, cisplatin, carboplatin) were eligible. Screening measures included (1) Pediatric Vestibular Symptom Questionnaire, (2) Modified Clinical Test of Sensory Interaction on Balance, and (3) Dynamic Visual Acuity.

Results: Vestibular screening failures were observed in 30 participants (60%). Patients with a brain tumor diagnosis were at increased risk for failures compared to nonbrain tumor patients (74.2% vs. 36.8%, P = 0.009). Patients who underwent brain surgery were at increased risk for failures compared to patients without brain surgery (71% vs. 42%, P = 0.043). Patients with a longer duration between end of treatment and vestibular screening had a reduced risk of failures, with an almost 20% decrease for each year between the time points (odds ratio = 0.812; 95% confidence interval: 0.683-0.964, P = 0.018). Receiving carboplatin correlated with a decreased risk of failure (P = 0.016), due to a negative correlation with other clinical risk factors (diagnosis of a brain tumor, major brain surgery) that are associated with vestibular screening failure.

Conclusion: Vestibular screening failures are highly prevalent in childhood cancer survivors who received ototoxic therapy. Broad screening of this population and further characterization of these patients are warranted.
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http://dx.doi.org/10.1002/pbc.26992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371968PMC
June 2018

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT.

Bone Marrow Transplant 2018 05 17;53(5):535-555. Epub 2018 Jan 17.

CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.
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http://dx.doi.org/10.1038/s41409-017-0055-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985976PMC
May 2018

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2018 Jan;16(1):66-97

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.
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http://dx.doi.org/10.6004/jnccn.2018.0001DOI Listing
January 2018