Association Between Laboratory Values and Adverse Events in Adults Post-Hematopoietic Stem Cell Transplant During and After Rehabilitation.

OBJECTIVE: The objective of this study was to examine the relationship between adverse events (AEs) and critical events (CEs) during and after rehabilitation in cancer patients post-hemopoietic stem cell transplant (HSCT) or bone marrow transplant (BMT) and to identify whether particular laboratory values are associated with increased risk of AEs or CEs. DESIGN: A retrospective chart review (2012-2017) of hospitalized patients ages 18-75 years who received a diagnosis of cancer and BMT or HSCT receiving rehabilitation services SETTING: Urban Midwest tertiary, research and academic hospital. PARTICIPANTS: In total, 99 hospitalized adults with HSCT or BMT participated in 300 rehabilitation sessions. INTERVENTIONS: Physical or occupational therapy using a symptom-based approach in which patient symptoms were monitored and therapy was adjusted in real time MAIN OUTCOME MEASURES: Incidence of AEs or CEs occurring during or within 48 hours of rehabilitation. RESULTS: A total of 300 rehabilitation sessions were carried out where 99.7% had 1 or more laboratory values outside reference range. In only 3.3% of therapy sessions an AE occurred during or within 2 hours of rehabilitation. Within 48 hours postrehabilitation, AEs occurred in 22.3% and CEs in 4%. No laboratory value was significantly associated with increased risk of AEs or CEs during rehabilitation. A hemoglobin <8.0 g/dL conferred an increased risk of AEs (odds ratio [OR], 2.85-6.89) depending on timeframe analyzed and overall risk of CE (OR, 3.75). Lower hemoglobin levels (<7.5 g/dL and <7.0 g/dL) did not increase this risk. Low platelets (<25 k/µL) increased the risk of AEs on day 1, 2 and overall (OR, 2.5-2.72) and overall risk of CEs (OR, 6.62). CONCLUSIONS: Our research demonstrates a low rate of AEs and CEs during or within 2 hours of rehabilitation but supports the need to monitor patients when hemoglobin is <8 g/dL or platelets are <25 k/µL due to the increased risk of events.

Utilization and Cost of Outpatient Rehabilitation Services for Pediatric Patients Treated for Acute Lymphoblastic Leukemia Using a Commercial Claims Database.

OBJECTIVE: To investigate the temporal trends and factors associated with outpatient rehabilitation utilization and costs for pediatric acute lymphoblastic leukemia (ALL). DESIGN: Deidentified administrative claims data and longitudinal health information on patients representing a mixture of ages, ethnicities, and geographic regions across the United States were accessed using Optum Labs Data Warehouse. Regression models were constructed to assess associations of outpatient rehabilitation with age, sex, race and ethnicity, year of diagnosis, and region. SETTING: Outpatient rehabilitation. PARTICIPANTS: 1000 Patients aged 1-30 years with a new diagnosis of ALL between 1993 and 2017 and continuous insurance coverage (N=1000). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Outpatient rehabilitation service utilization and cost based on reimbursed charge codes, summarized over 36 months after cancer diagnosis. RESULTS: In 1000 patients, utilization of outpatient rehabilitation services increased from 20% in 1993-2002 to 55% in 2013-2017. In the earliest era examined, physical and/or occupational therapy was provided to 18% and increased to 54% in the latest years. Speech service utilization remained between 5%-8% across timepoints. Inflation-adjusted cost for provision of services did not change significantly across time and remained low, accounting for a median of 1.3% (Q1, Q3 0.3, 3.4) of total treatment cost in 1993-2002 and decreasing to a median 0.4% (Q1, Q3, 0.1, 1.0) in 2013-2017. Age 1 to 5 years at ALL diagnosis was associated with increased rehabilitation visit number and cost, and treatment in the Midwest was associated with increased likelihood of outpatient rehabilitation service utilization compared to other geographic regions. CONCLUSIONS: Outpatient rehabilitation services are being increasingly provided to patients with ALL at a relatively low cost per patient, yet geographic variability in care utilization is evident. These services do not add excessively to the overall cost of leukemia care and thus cost containment should not be an excuse to limit access.

Switching to Bortezomib may Improve Recovery From Severe Vincristine Neuropathy in Pediatric Acute Lymphoblastic Leukemia.

PURPOSE: The purpose of this study was to evaluate the impact of switching patients being treated for acute lymphoblastic leukemia (ALL) from vincristine to bortezomib. PATIENTS AND METHODS: A total of 20 patients with ALL were switched from vincristine to bortezomib (1.3 mg/m/dose) because of worsening neuropathy despite physical therapy interventions (n=18) or at increased risk of neuropathy (n=2). Relapse rates were compared with 56 vincristine-only patients matched by prognostic factors. Maintenance blood counts in bortezomib patients were compared with cooperative group data using vincristine during maintenance. In addition, 6 evaluable patients were assessed for neuropathy using the pediatric-modified total neuropathy score. Neuropathy scores were collected during treatment with vincristine and after switching to bortezomib. RESULTS: After a median follow-up of 3.5 years the relapse rate in patients switched to bortezomib was nonsignificantly different than those remaining on vincristine. Patients on monthly bortezomib had statistically significantly lower platelet counts that did not require transfusions or dose adjustment. Total neuropathy for all 6 cases decreased significantly when switched to bortezomib from vincristine (P=0.015), with motor neuropathy declines in 5 of 6 subjects. CONCLUSIONS: Bortezomib substitution for vincristine in ALL treatment is a potential strategy to mitigate severe vincristine neuropathy. These findings should be confirmed in a randomized clinical trial to further assess benefits and risks of this approach.

Short-Term Recovery of Balance Control: Association With Chemotherapy-Induced Peripheral Neuropathy in Pediatric Oncology.

PURPOSE: To describe the incidence and short-term recovery of balance control in children and adolescents receiving neurotoxic treatment for noncentral nervous system cancers and to investigate the association of chemotherapy-induced peripheral neuropathy and balance control. METHODS: Sixty-five children and adolescents diagnosed with leukemia, lymphoma, or other solid tumors were tested 3 to 6 months into treatment and 3 and 6 months following treatment using the Bruininks-Oseretsky Balance Subscale and Pediatric Modified Total Neuropathy Scale scores of chemotherapy-induced peripheral neuropathy (CIPN). RESULTS: Seventy-eight percent of the participants scored 1 standard deviation or more below population means on the balance subscale while on treatment, and this improved to 53% by 6 months posttreatment, with the leukemia group performing worse at both time points. On-treatment balance scores were moderately associated with motor CIPN, while at 6 months posttreatment they were more closely associated with sensory CIPN. CONCLUSIONS: Mild to moderate balance impairments improve but can persist, even when CIPN has improved, 6 months after treatment for childhood cancer.

Short-term recovery of chemotherapy-induced peripheral neuropathy after treatment for pediatric non-CNS cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side effect of pediatric cancer treatment. The presentation of CIPN, trajectory and completeness of recovery over the first 6 months postchemotherapy, and the influence of patient and treatment characteristics on recovery are described. PATIENTS AND METHODS: Sixty-seven children and adolescents treated for non-CNS cancers were evaluated for CIPN using the pediatric modified total neuropathy score (ped-mTNS) while on treatment and 3 and 6 months postchemotherapy. Differences between diagnostic groups and treatment type were evaluated as well as change in scores over time. Risk factors for on-treatment and persistent CIPN at 6 months were identified. RESULTS: Overall, ped-mTNSs were in the abnormal range for 86.5% during treatment and scores decreased over time (initial 9.3 ± 0.6, 6 months 4.3 ± 0.4; F = 38.14, P < 0.001). By 6 months posttreatment, mean scores and percentage of children with abnormal scores were reduced to 2.4 ± 0.3 and 11.5%, respectively, in the ALL group, but remained higher at 5.7 ± 0.7 and 57%, respectively, for lymphoma, and 5.2 ± 1.0 and 60%, respectively, for other solid tumors. At 6 months posttreatment, light touch deficits and foot strength deficits remained in 19.4 and 59.7%, respectively, compared with only 4.9 and 9.8% of the control population. Subjects who were older at exposure, female, or who received etoposide in addition to vincristine were at higher risk for on-treatment CIPN. On-treatment sensory abnormalities were associated with increased risk of persistent CIPN. CONCLUSION: While CIPN improves in most pediatric patients, significant numbers, especially those treated for lymphoma or other solid tumors, have remaining neuropathic signs and symptoms 6 months posttreatment.

Use of a Fitness Tracker to Promote Physical Activity in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Children with cancer identify fatigue as a pervasive symptom, which increases during the corticosteroid pulse in acute lymphoblastic leukemia (ALL) maintenance. The FitBit is a fitness tracker that downloads activity measurements to the Internet in real time. In this feasibility study, we explored if children who received daily FitBit coaching for 2 weeks before a maintenance steroid pulse had an increase in steps per day and determined the relationship between steps per day prepulse and fatigue postpulse. PROCEDURE: Seventeen children in ALL maintenance, aged 6-15, wore the FitBit for 3 days to establish a baseline. A tailored weekly step goal was then set with the child and parent. Daily emails with feedback and FitBit screenshots were sent over the 2-week intervention. Self-report of fatigue was measured at baseline, after 2 weeks (i.e. before the steroid pulse), and after 5 days of steroids. RESULTS: There was a trend toward increased steps per day from weeks 1-2 (P = 0.079); fatigue was low and did not increase during the corticosteroid pulse. A significant correlation (r = -0.66, P = 0.005) was found between the steps per day during week 2 and fatigue after the steroid pulse with higher steps associated with lower fatigue. CONCLUSIONS: The intervention was feasible in this small sample. The average steps each time period (week 1, week 2, and during steroids) was over 10,000, demonstrating that children with ALL can be active during treatment. Physical activity may be protective of fatigue during a corticosteroid pulse.

Toward a National Initiative in Cancer Rehabilitation: Recommendations From a Subject Matter Expert Group.

The health care delivery system in the United States is challenged to meet the needs of a growing population of cancer survivors. A pressing need is to optimize overall function and reduce disability in these individuals. Functional impairments and disability affect most patients during and after disease treatment. Rehabilitation health care providers can diagnose and treat patients' physical, psychological, and cognitive impairments in an effort to maintain or restore function, reduce symptom burden, maximize independence and improve quality of life in this medically complex population. However, few care delivery models integrate comprehensive cancer rehabilitation services into the oncology care continuum. The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health with support from the National Cancer Institute and the National Center for Medical Rehabilitation Research convened a subject matter expert group to review current literature and practice patterns, identify opportunities and gaps regarding cancer rehabilitation and its support of oncology care, and make recommendations for future efforts that promote quality cancer rehabilitation care. The recommendations suggest stronger efforts toward integrating cancer rehabilitation care models into oncology care from the point of diagnosis, incorporating evidence-based rehabilitation clinical assessment tools, and including rehabilitation professionals in shared decision-making in order to provide comprehensive cancer care and maximize the functional capabilities of cancer survivors. These recommendations aim to enable future collaborations among a variety of stakeholders to improve the delivery of high-quality cancer care.

Gait Patterns in Children With Cancer and Vincristine Neuropathy.

PURPOSE: Children treated with vincristine often develop chemotherapy-induced peripheral neuropathy (CIPN), but effects of CIPN on gait have not been reported. METHODS: Gait variables of 52 children/adolescents treated for non-central nervous system cancers with CIPN were compared with an age- and sex-matched control group. Gait data were collected via GaitRite walkway before and after completing a 6-minute walk test (6MWT). Ankle range-of-motion (ROM) measures, balance, and strength tests were also completed. RESULTS: Participants with CIPN had decreased velocity and step length. Ankle ROM and balance explained variability in step length. Both groups increased self-selected velocity after the 6MWT, but participants with cancer walked with slower velocity, shorter step length, and decreased cadence. Strength, neuropathy, and self-selected velocity measured before the 6MWT explained variability in 6MWT scores. CONCLUSIONS: Ankle ROM and balance are important factors when treating step length deficits, whereas strength is also an important consideration for walking capacity.

Impact of the COVID-19 pandemic on utilization and cost for care of pediatric and young adult ALL.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and among the most common malignancies in young adults and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood and young adult ALL in regard to utilization and cost of care among commercially insured individuals in the United States. RESULTS: Utilizing a commercial insurance claims database, 529 pediatric and young adult patients were identified who were diagnosed with ALL between January 2016 and March 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost during the initial 8 months of therapy. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric and young adult ALL was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric and young adult populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric and young adult cancer.

Healthcare cost and utilization for chimeric antigen receptor (CAR) T-cell therapy in the treatment of pediatric acute lymphoblastic leukemia: A commercial insurance claims database analysis.

BACKGROUND: B-lineage acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. With the introduction of novel cellular therapies, cost of care is a critical component and the financial burden experienced by patients and society requires evaluation. AIMS: This study aims to assess the utilization and cost of care for chimeric antigen receptor T-cell (CAR-T) therapy for pediatric ALL patients with commercial insurance coverage in the United States. METHODS AND RESULTS: Using de-identified commercial insurance data from the OptumLabs® Data Warehouse, a cohort of 37 patients, aged 1-25 years, with B-ALL treated with CAR-T therapy between Oct 2016 and Dec 2021 in the United States was identified. Cost was evaluated for a 90 day period encompassing CAR-T infusion and by administration and complication characteristics. Among the 37 identified B-ALL patients that received a CAR-T product infusion, 14 patients were female, median age at administration was 13 years. The median 90-day total cost was $620,500 (Mean: $589,108). Inpatient cost accounted for approximately 71% of the total cost with an average of 28 inpatient days per patient. Although inpatient cost was slightly higher in the older age group (aged 10-25 years) and in patients with a code for cytokine release syndrome (CRS), these differences were not statistically significant. CONCLUSION: This real-world cost analysis shows for the first time the encompassing cost of CAR-T therapy for pediatric B-ALL patients in the US with commercial insurance. This study provides a valuable benchmark that can be used to analyze the financial implications of CAR-T therapy for pediatric B-ALL therapy on health systems.

The pediatric-modified total neuropathy score: a reliable and valid measure of chemotherapy-induced peripheral neuropathy in children with non-CNS cancers.

BACKGROUND: Neurotoxicity is a common side-effect of cancer treatment, but no scales have been validated for the pediatric population. The objective of this study was to test the reliability and validity of the pediatric modified-Total Neuropathy Scale (ped-mTNS) to measure chemotherapy-induced peripheral neuropathy in school-aged children. METHODS: Forty-one subjects aged 5-18 years undergoing chemotherapy with vincristine or cisplatin and 41 age- and gender-matched controls completed study measures. Subjects were tested with the ped-mTNS at a specified time during treatment. Standardized measures of balance and hand function were completed concurrently. Internal consistency of the ped-mTNS was evaluated using Chronbach's alpha. Validity was tested by comparing case and control ped-mTNS scores as well as testing the hypothesis that ped-mTNS scores would be associated with scores on tests of balance and manual dexterity. Inter-rater and test-retest reliability were each assessed in a subset of 10 subjects. RESULTS: Twenty-three subjects with acute lymphoblastic leukemia, six with lymphoma, and 12 with solid tumors completed measures along with 41 age- and gender-matched controls. Internal consistency was acceptable with a Chronbach's alpha of 0.76. Children undergoing treatment for cancer had significantly worse scores on the ped-mTNS compared to controls (subjects, 8.7 ± 4.2; controls, 1.4 ± 0.9; p < 0.001). As hypothesized, scores on the ped-mTNS were associated with measures of balance and manual dexterity. Inter-rater and test-retest reliability was acceptable (intraclass correlation coefficients >0.9 each). CONCLUSIONS: The ped-mTNS is a reliable and valid measure of chemotherapy-induced peripheral neuropathy in school-aged children that is associated with relevant functional limitations.

Rehabilitation interventions for the management of breast cancer-related lymphedema: developing a patient-centered, evidence-based plan of care throughout survivorship.

PURPOSE: A work group from the American Physical Therapy Association Academy of Oncologic Physical Therapy developed and published a clinical practice guideline (CPG) to aid clinicians in identifying interventions for individuals with breast cancer-related lymphedema (BCRL). This guideline reviewed the evidence for risk mitigation and volume reduction beginning at cancer diagnosis and continuing through survivorship. Application of CPGs can be challenging due to the variability of clinical settings, heterogeneous patient populations, and range of rehabilitation clinician expertise. The purpose of this paper is to assist these clinicians in implementing the recommendations from the CPG to develop a patient-centered, evidence-based plan of care. METHODS/RESULTS: This publication presents important considerations for the implementation of recommended rehabilitation interventions across the trajectory of BCRL. CONCLUSION: Current evidence supports specific interventions to treat or mitigate the risk for the various stages of BCRL. As clinicians implement these recommendations into practice, they also need to address other impairments that may exist in every individual. Continued collaboration between clinicians and researchers is necessary to further develop optimal treatment modalities and parameters. IMPLICATIONS FOR CANCER SURVIVORS: By implementing evidence-based interventions as outlined in the CPG, clinicians can improve the quality of care for survivors of breast cancer.

Patient education for breast cancer-related lymphedema: a systematic review.

PURPOSE: The aim was to identify the impact of the (a) components of breast cancer-related lymphedema (BCRL) educational content, (b) modes of education, and (c) timing of education on arm volume, quality of life, function, complications associated with BCRL, adherence to interventions, and knowledge acquisition in individuals diagnosed with breast cancer (BC). METHODS: This review followed the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines (PROSPERO CRD42021253084). Databases searched included PubMed, CINAHL, Web of Science, Google Scholar, and Scopus from January 2010 to December 2021. Study quality and bias were assessed using the American Physical Therapy Association's Critical Appraisal Tool for Experimental Intervention Studies. RESULTS: Forty-five studies were eligible, and 15 met the inclusion criteria (4 acceptable and 11 low quality). This review was unable to determine the optimal content, mode, and timing for BCRL education across survivorship. Content included a brief overview of BCRL, early signs and symptoms, risk reduction practices, and a point of contact. Delivery was multi-modal, and knowledge acquisition was rarely assessed. Education was provided pre/post operatively and after BCRL developed. CONCLUSIONS: Individualized BCRL education via a multi-modal approach, repeated at multiple time points, and assessment of survivors' knowledge acquisition is recommended. Consideration of the survivors' phase of treatment, content volume, and time required to complete the program is advised when developing the educational intervention. IMPLICATIONS FOR CANCER SURVIVORS: Survivors of BC may need to advocate for BCRL education based on their individual risk and needs, request a point of contact for questions/follow up, and express their preferred style of learning.

Impact of the COVID-19 Pandemic on Utilization and Cost for Care of Pediatric ALL.

Objective: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood ALL in regard to utilization and cost of care. Results: Utilizing a commercial insurance claims database, 529 pediatric patients were identified who were diagnosed with ALL and completed their initial 8 months of treatment between January 2016 and December 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric ALL is largely inflexible and was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric cancer.

Real-World Cost of Pediatric Acute Lymphoblastic Leukemia Care Among Commercially Insured Individuals in the United States: Effect of Era and Age at Diagnosis.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Five-year survival is approaching 90%. In efforts to further improve outcomes, it is critical to consider the cost of ALL care. MATERIALS AND METHODS: Commercial insurance data from OptumLabs Data Warehouse were used to identify patients with ALL, age 1-30 years, diagnosed in 1993-2017 in the United States, with 36 months of continuous insurance coverage. Patients treated with hematopoietic cell transplantation were excluded. Inpatient and outpatient utilization and cumulative reimbursements (inflation-adjusted to December 2020) were computed 8 and 36 months from diagnosis and stratified by age (1-9, 10-12, and ≥ 13 years) as proxies for National Cancer Institute risk groups. Regression models were constructed to assess associations with demographic and clinical characteristics. RESULTS: Among 927 patients (median age, 6 years; interquartile range, 3-12 years; 43% female), individuals age ≥ 10 years had 23-25 more inpatient days and 22 more outpatient encounters compared with younger patients. The 36-month median cost was $394,000 (USD) (interquartile range, $256,000-$695,000 [USD]), and 64% of the total cost was incurred during the initial 8 months. The 36-month cost was 1.5-fold higher for those age 10-12 years and 1.7-fold higher for those age ≥ 13 years compared with 1-9 years. The cost for those diagnosed in 2013-2017 was 70% higher compared with 1993-2002, and was not different on the basis of sex, race, or ethnicity. CONCLUSION: Older age was associated with higher utilization and cost, and the cost of treatment increased significantly over time. These data provide valuable benchmarks for future studies examining the cost-benefit of ALL therapy modifications.

Assessment of Pediatric Chemotherapy-Induced Peripheral Neuropathy Using a New Patient-Reported Outcome Measure: The P-CIN.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is commonly experienced by children receiving neurotoxic chemotherapy. No validated pediatric CIPN patient-reported outcome (PRO) measures exist. Purpose: To test sensitivity, internal consistency reliability, content and convergent validity, and feasibility of the Pediatric Chemotherapy-Induced Neuropathy (P-CIN), an electronic PRO measure for assessing CIPN in children who received neurotoxic chemotherapy. Method: Five experts evaluated content validity of the 14-item P-CIN. Children 5 to 17 years old with CIPN (N = 79) completed the P-CIN via tablet computer; a subset (n = 26) also underwent neurological examinations using the Pediatric-Modified Total Neuropathy Score. Following preliminary analyses, one item was deleted and three others modified. The revised P-CIN was retested with patients (n = 6) who also completed the Bruininks-Oseretsky Test of Motor Proficiency motor function assessment. Means, item response ranges, standard deviations, content validity indexes, Cronbach's alphas, and correlation coefficients were calculated. Results: Mean participant age was 11.25 (SD = 4.0) years. Most had acute leukemia (62.5%) and received vincristine (98.7%). Content validity index coefficients ranged from .80 to 1.0 (p = .05). For 9 of 14 items, responses ranged from 0 to 4 or 5; response ranges for toe numbness, pick up a coin, and three of four pain items were 0 to 3. After deleting one item, Cronbach's alpha coefficient was .83. P-CIN scores were strongly associated with Pediatric-Modified Total Neuropathy Score (r = .52, p < .01) and Bruininks-Oseretsky Test of Motor Proficiency (r = -.83, p = .04) scores. Sixty-eight percent of children 6 to 17 years old completed P-CIN independently. Discussion: Preliminary evidence suggests that the 13-item P-CIN is internally consistent, is valid, and can be completed independently by children ≥ 6 years. However, we recommend additional testing.

Characteristics and patterns of pediatric chemotherapy-induced peripheral neuropathy: A systematic review.

This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and patterns described in studies of children who received neurotoxic chemotherapy to treat cancer. PubMed, CINAHL, PsycINFO, and Embase were searched for articles published 2009 - 2019, yielding 861. Forty-two papers met the eligibility criteria, including 31 that described characteristics and patterns of vincristine-induced CIPN. Fifty-seven percent of articles were of low to moderate quality; measurement flaws were the most common limitations. The reported CIPN incidence varies widely (2.8%-100%) depending on risk factors (e.g., race) and the measurement approach. Incidence rates of sensory, motor, autonomic CIPN, and pain were 12-28%, 50-72%, 0.8-83% and 5.7-44%, respectively. The evidence suggests that sensory and motor neuropathy, pain, and functional deficits are common and can persist into adulthood. Caucasian race is a risk factor and, contrary to prior thinking, cumulative chemotherapy dosage alone does not predict CIPN severity. The influence of other risk factors is less clear, and studies to date have not explored potential interactions among race, genetics, age, sex, drug metabolism, and nutritional status, among other factors.