First name
Claire
Last name
Carlson

Title

Long-Term Kidney and Cardiovascular Complications in Pediatric Cancer Survivors.

Year of Publication

2023

Number of Pages

89-97.e1

Date Published

04/2023

ISSN Number

1097-6833

Abstract

OBJECTIVE: The objective of this study was to describe the burden of adverse kidney and hypertension outcomes in patients evaluated by pediatric nephrology in a multidisciplinary survivorship clinic.

STUDY DESIGN: Retrospective chart review of all patients followed up by nephrology in our multidisciplinary survivorship clinic from August 2013 to June 2021. Data included clinic blood pressure, longitudinal ambulatory blood pressure monitoring (ABPM), echocardiography, serum creatinine, and first-morning urine protein/creatinine ratios. For patients with multiple ABPMs, results of initial and most recent ABPMs were compared.

RESULTS: Of 422 patients followed in the multidisciplinary cancer survivorship clinic, 130 were seen by nephrology. The median time after therapy completion to first nephrology visit was 8 years. The most common diagnoses were leukemia/myelodysplastic syndrome (27%), neuroblastoma (24%), and Wilms tumor (15%). At the last follow-up, 68% had impaired kidney function, 38% had a clinical diagnosis of hypertension, and 12% had proteinuria. There were 91 ABPMs performed in 55 (42%) patients. Patients with multiple ABPMs (n = 21) had statistically significant reductions in overall median blood pressure loads: systolic initial load 37% vs most recent 10% (P = .005) and diastolic load 36% vs 14% (P = .017). Patients with impaired kidney function were more likely to have received ifosfamide. Patients with hypertension were more likely to have received total body irradiation or allogeneic stem cell transplant.

CONCLUSIONS: History of leukemia/myelodysplastic syndrome, neuroblastoma, and Wilms tumor was frequent among survivors seen by nephrology. There was significant improvement in cardiovascular measures with increased recognition of hypertension and subsequent treatment.

DOI

10.1016/j.jpeds.2022.10.029

Alternate Title

J Pediatr

PMID

36336006
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Title

Long-term kidney and cardiovascular complications in pediatric cancer survivors.

Year of Publication

2022

Number of Pages

Date Published

11/2022

ISSN Number

1097-6833

Abstract

OBJECTIVE: To describe the burden of adverse kidney and cardiovascular outcomes in patients evaluated by pediatric nephrology in a multidisciplinary survivorship clinic.

STUDY DESIGN: Retrospective chart review of all patients followed by nephrology in our multidisciplinary survivorship clinic from 8/2013-6/2021. Data included clinic blood pressure (BP), longitudinal ambulatory blood pressure monitoring (ABPM), echocardiography, serum creatinine, and first-morning urine protein/creatinine ratios. For patients with multiple ABPMs, results of initial and most recent ABPMs were compared.

RESULTS: Of 422 patients followed in the multidisciplinary cancer survivorship clinic, 130 were seen by nephrology. Median time after therapy completion to first nephrology visit was 8 years. The most common diagnoses were leukemia/myelodysplastic syndrome (27%), neuroblastoma (24%), and Wilms tumor (15%). At last follow-up, 68% had impaired kidney function, 38% had a clinical diagnosis of hypertension, and 12% had proteinuria. There were 91 ABPMs performed in 55 (42%) patients. Patients with multiple ABPMs (n=21) had statistically significant reductions in overall median BP loads: systolic initial load 37% vs. most recent 10% (p=0.005) and diastolic load 36% vs. 14% (p=0.017). Patients with impaired kidney function were more likely to have received ifosfamide. Patients with hypertension were more likely to have received total body irradiation or allogeneic stem cell transplant.

CONCLUSIONS: History of leukemia/myelodysplastic syndrome, neuroblastoma, and Wilms tumor were frequent among survivors seen by nephrology. There was significant improvement in cardiovascular measures with increased recognition of hypertension and subsequent treatment.

DOI

10.1016/j.jpeds.2022.10.029

Alternate Title

J Pediatr

PMID

36336006
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Title

Late effects in survivors of high-risk neuroblastoma following stem cell transplant with and without total body irradiation.

Year of Publication

2021

Number of Pages

e29537

Date Published

2021 Dec 31

ISSN Number

1545-5017

Abstract

<p><strong>BACKGROUND: </strong>Neuroblastoma is the most common extracranial solid tumor in children. Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI.</p>

<p><strong>PROCEDURE: </strong>Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit.</p>

<p><strong>RESULTS: </strong>All 48 survivors of BMT for high-risk neuroblastoma had numerous late effects of therapy, with 73% having between five and 10 late effects. TBI impacted some late effects significantly, including growth hormone deficiency (GHD), bone outcomes, and cataracts.</p>

<p><strong>CONCLUSION: </strong>Although high-risk neuroblastoma survivors treated with TBI have significant late effects, those treated without TBI also continue to have significant morbidity related to high-dose chemotherapy and local radiation. A multidisciplinary care team assists in providing comprehensive care to those survivors who are at highest risk for significant late effects.</p>

DOI

10.1002/pbc.29537

Alternate Title

Pediatr Blood Cancer

PMID

34971017
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Title

Kidney Outcomes and Hypertension in Survivors of Wilms Tumor: A Prospective Cohort Study.

Year of Publication

2020

Number of Pages

Date Published

2020 Dec 05

ISSN Number

1097-6833

Abstract

<p>Supported by a Pilot Grant from the Children's Hospital of Philadelphia Center for Pediatric Clinical Effectiveness (to D.C.). D.C. is also supported by the NIH/NIDDK (K23 DK125670). G.T. was supported by the NIH/NIDDK (K23 DK106428). Ja.G. was supported by NIH/NIDDK (K08 DK110536). M.D. was supported by the NIH/NIDDK (K23 DK093556). The NIH and NIDDK had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the official view of the NIDDK nor NIH. G.T. serves on the scientific advisory boards for Allena Pharmaceuticals, Novome Biotechnology, and Dicerna Pharmaceuticals and serves as a consultant for Alnylam Pharmaceuticals, all of which are unrelated to this work. M.D. receives research funding from Mallinckrodt unrelated to this work. The other authors declare no conflicts of interest. Portions of this study were presented at the Pediatric Academic Society annual meeting, May 5-8, 2020, Toronto, Canada.</p>

<p><strong>OBJECTIVE: </strong>To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT).</p>

<p><strong>STUDY DESIGN: </strong>This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with pre-existing hypertension, prior dialysis or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90 percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for KIM-1, IL-18, EGF, albumin, and creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the bedside CKiD equation. Recent kidney ultrasounds and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy (LVH), respectively. Clinical follow-up data was collected for approximately 2 years following study enrollment.</p>

<p><strong>RESULTS: </strong>Thirty-two participants (median age 13.6 [IQR: 10.5-16.3] years; 75% ≥Stage 3 WT) were evaluated at a median of 8.7 years (IQR: 6.5-10.8) post-therapy; 29 participants underwent unilateral radical nephrectomy, two bilateral partial nephrectomy, and one radical and contralateral partial nephrectomy. 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 ml/min/1.73m (IQR: 84.6-114.0; 11 (34%) had an eGFR &lt;90). Abnormal ABPM results were found in 22/29 participants (76%), masked hypertension in 10/29 (34%), and microalbuminuria in 2/32 (6%). 22/32 (69%) participants had abnormal EGF; few had abnormal KIM-1 or IL-18. Seven participants with previous unilateral nephrectomy lacked compensatory contralateral kidney hypertrophy. None had LVH.</p>

<p><strong>CONCLUSION: </strong>In survivors of WT, adverse kidney outcomes were common and should be closely monitored.</p>

DOI

10.1016/j.jpeds.2020.12.005

Alternate Title

J Pediatr

PMID

33290810
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Title

Attitudes Toward Fertility Preservation Among Transgender Youth and Their Parents.

Year of Publication

2020

Number of Pages

Date Published

2020 Apr 29

ISSN Number

1879-1972

Abstract

<p><strong>PURPOSE: </strong>While gender-affirming hormones (GAH) may impact the fertility of transgender and gender diverse (TGGD) youth, few pursue fertility preservation (FP). The objective of this study is to understand youth and parent attitudes toward FP decision-making.</p>

<p><strong>METHODS: </strong>This study is a cross-sectional survey of youth and parents in a pediatric, hospital-based gender clinic from April to December 2017. Surveys were administered electronically, containing 34 items for youth and 31 items for parents regarding desire for biological children, willingness to delay GAH for FP, and factors influencing FP decisions.</p>

<p><strong>RESULTS: </strong>The mean age of youth (n&nbsp;= 64) was 16.8&nbsp;years, and 64% assigned female at birth; 46 parents participated. Few youth (20%) and parents (13%) found it important to have biological children or grandchildren, and 3% of youth and 33% of parents would be willing to delay GAH for FP. The most common factor influencing youth FP decision-making was discomfort with a body part they do not identify with (69%), and for the parents, whether it was important to their child (61%). In paired analyses, youth and their parents answered similarly regarding youth desire for biological children and willingness to delay GAH for FP.</p>

<p><strong>CONCLUSIONS: </strong>The majority of TGGD youth and parents did not find having biological offspring important and were not willing to delay GAH for FP. Discomfort with reproductive anatomy was a major influencing factor for youth FP decision-making and their child's wishes was a major factor for parents. Future qualitative research is needed to understand TGGD youth and parent attitudes toward FP and to develop shared decision-making tools.</p>

DOI

10.1016/j.jadohealth.2020.02.027

Alternate Title

J Adolesc Health

PMID

32359942
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Title

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer.

Year of Publication

2015

Number of Pages

1420-4

Date Published

2015 Nov

ISSN Number

1527-3792

Abstract

<p><strong>PURPOSE: </strong>Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.</p>

<p><strong>MATERIALS AND METHODS: </strong>We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values.</p>

<p><strong>RESULTS: </strong>A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6&nbsp;months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation.</p>

<p><strong>CONCLUSIONS: </strong>The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation.</p>

DOI

10.1016/j.juro.2015.04.117

Alternate Title

J. Urol.

PMID

26032139
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