Publications by authors named "Sue C Kaste"

174 Publications

Total Hip Arthroplasty in Adolescents and Young Adults for Management of Advanced Corticosteroid-Induced Osteonecrosis Secondary to Treatment for Hematologic Malignancies.

J Arthroplasty 2020 Oct 19. Epub 2020 Oct 19.

Division of Orthopaedics, Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN.

Background: Osteonecrosis of the femoral head (ONFH) is a potentially severe toxicity associated with glucocorticoid treatment for pediatric hematologic malignancy. We examined clinical outcomes of THA in adolescents and young adults treated for hematologic malignancies who developed advanced ONFH.

Methods: In a single-institution cohort, we retrospectively reviewed medical records and imaging for perioperative complications, reoperations, functional assessment at last follow-up, and radiological outcomes. Twenty-seven patients (41 hips) underwent THA (bilateral in 14 patients). There were 11 males. Median (interquartile range [IQR]) age at primary diagnosis was 14.9 years [1.8-18.9]. The median (IQR) age at THA was 19.8 years [14.6-30.3]. Mean (range) post-THA follow-up was 111.5 months (65.4-165.8).

Results: Perioperative complications included one intraoperative calcar fracture that was secured with a cerclage wire and one posterior hip dislocation that occurred 6 days postoperatively, requiring closed reduction. One hip required a revision 21.1 months post-THA due to a fractured ceramic liner. The radiographic review was available for 38 of 41 hips and demonstrated none with loosening, subsidence, or osteolysis; nine developed periacetabular stress shielding. Incidence of stress shielding was associated with increased postoperative pain (P = .0130). There was a significant functional improvement in range of motion (ROM), pain, use of supports, participation in school, work, and sports, and use of pain medication from preoperative to postoperative clinical visits (P < .001).

Discussion: Total hip arthroplasty in adolescents and young adults offers symptomatic and functional improvement in patients with ONFH. We found it to be safe with low perioperative complication rates even in patients undergoing active treatment for malignancy.

Level Of Evidence: Level IV, case series study. See Instructions for authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1016/j.arth.2020.10.019DOI Listing
October 2020

Spinal changes after craniospinal irradiation in pediatric patients.

Pediatr Blood Cancer 2020 12 3;67(12):e28728. Epub 2020 Oct 3.

Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI).

Procedure: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated.

Results: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis.

Conclusions: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood.
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http://dx.doi.org/10.1002/pbc.28728DOI Listing
December 2020

Team approach: Management of osteonecrosis in children with acute lymphoblastic leukemia.

Pediatr Blood Cancer 2020 11 29;67(11):e28509. Epub 2020 Aug 29.

Division of Orthopaedic Oncology, Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

With current treatments for acute lymphoblastic leukemia (ALL), the overall prognosis for survival is favorable. Increasing emphasis is placed on recognizing and managing the long-term consequences of ALL and its treatment, particularly involving osteonecrosis. Early osteonecrosis diagnosis and management may improve outcomes and is best accomplished through coordinated teams that may include hematologic oncologists, radiologists, orthopedic surgeons, physical therapists, and the patient and their family. Magnetic resonance imaging is the "gold standard" for diagnosis of early-stage and/or multifocal osteonecrosis. Treatments for osteonecrosis in ALL patients are risk stratified and may include observation, corticosteroid or chemotherapy adjustment, and pharmaceutical or surgical approaches.
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http://dx.doi.org/10.1002/pbc.28509DOI Listing
November 2020

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies.

Eur J Cancer 2020 09 11;137:204-213. Epub 2020 Aug 11.

Departments of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Departments of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; The Departments of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

Background: Talazoparib combined with irinotecan and temozolomide demonstrated efficacy in a murine Ewing sarcoma model. Based on these data, we conducted a phase I trial of talazoparib and irinotecan with/without temozolomide in paediatric patients with recurrent/refractory solid malignancies.

Patients And Methods: Cohorts of 3-6 patients with recurrent/refractory solid malignancies received escalating doses of oral talazoparib and intravenous irinotecan (arm A) and oral talazoparib, oral temozolomide and intravenous irinotecan (arm B) in a 3 + 3 design. Talazoparib was administered on days 1-6, and intravenous irinotecan and oral temozolomide were administered on days 2-6, of a 21-day course. Serum for talazoparib and irinotecan pharmacokinetics was obtained during course 1. UGT1A1 polymorphism and Schlafen family member 11 (SLFN11) immunohistochemical staining were performed.

Results: Forty-one patients (20 males; median age, 14.6 years; 24 with recurrent disease) were evaluable for dose escalation. Twenty-nine and 12 patients were treated on arm A and arm B, respectively, for a total of 208 courses. The most common diagnosis was Ewing sarcoma (53%). The most common ≥grade III haematologic toxicities in arms A and B included neutropenia (78% and 31%, respectively) and thrombocytopenia (42% and 31%, respectively). In arms A and B, febrile neutropenia (24% and 14%, respectively) and diarrhoea (21% and 7%, respectively) were the most common ≥grade III non-hematologic toxicities. Six patients (Ewing sarcoma [5 patients] and synovial sarcoma [1 patient]) had a response (1 with a complete response, 5 with a partial response). The objective response rates were 10.3% (arm A) and 25% (arm B). Pharmacokinetic testing demonstrated no evidence of drug-drug interaction between talazoparib and irinotecan. UGT1A1 was not related to response. SLFN11 positivity was associated with best response to therapy.

Conclusions: The combination of talazoparib and irinotecan with/without temozolomide is feasible and active in Ewing sarcoma, and further investigation is warranted.
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http://dx.doi.org/10.1016/j.ejca.2020.06.014DOI Listing
September 2020

Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors.

Pediatr Blood Cancer 2020 10 26;67(10):e28617. Epub 2020 Jul 26.

Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Background: We modeled height after craniospinal irradiation (CSI) in pediatric patients with central nervous system (CNS) embryonal tumors to identify factors that impair stature.

Procedure: During 1996-2012, 212 pediatric patients (131 male) with CNS embryonal tumors received postoperative CSI: 23.4 Gy (n = 147) or ≥36 Gy (n = 65), similar postirradiation chemotherapy, and were followed for at least 5 years without tumor progression or other event. The group was further characterized by age at CSI and hormone-replacement therapy received. Models were developed to identify factors associated with growth impairment and estimate final height.

Results: With median follow up of 10.2 years (range 5.0-20.4 years), the mean final height z-scores at 18 years of age, compared to United States standards, were -1.3 for female and -1.5 for male survivors. Younger age at the time of CSI, higher CSI dose, and female sex were associated with height impairment. Factors associated with higher growth rates before 15 years of age were older age at CSI, male sex, CSI dose < 36 Gy, replacement therapy for growth hormone (GH) and central adrenal insufficiency, and white race. Growth after age 15 in male survivors was associated with treatment of gonadotropin deficiency. Linear mixed-effects models were developed using clinical factors to estimate final height, demonstrate the unique growth curve of this cohort, and interactions between clinical variable and radiation dose.

Conclusions: CSI significantly impaired height at current doses used to treat standard- or high-risk CNS embryonal tumors. Measures to reduce the impact of CSI on height should be sought, with our models serving as benchmarks.
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http://dx.doi.org/10.1002/pbc.28617DOI Listing
October 2020

Evaluation of Chest Radiographs of Children with Newly Diagnosed Acute Lymphoblastic Leukemia.

J Pediatr 2020 08;223:120-127.e3

Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN. Electronic address:

Objective: To evaluate the diagnostic yield of baseline chest radiographs (CXRs) of children with acute lymphoblastic leukemia (ALL).

Study Design: We reviewed the CXR findings at diagnosis for 990 patients aged 1-18 years with ALL treated during the Total XV and XVI studies at St. Jude Children's Research Hospital and evaluated the associations of these findings with clinical characteristics and initial management.

Results: Common findings were peribronchial/perihilar thickening (n = 187 [19.0%]), pulmonary opacity/infiltrate (n = 159 [16.1%]), pleural effusion/thickening (n = 109 [11.1%]), mediastinal mass (n = 107 [10.9%]), and cardiomegaly (n = 68 [6.9%]). Portable CXRs provided results comparable with those obtained with 2-view films. Forty of 107 patients with a mediastinal mass (37.4%) had tracheal deviation/compression. Mediastinal mass, pleural effusion/thickening, and tracheal deviation/compression were more often associated with T-cell ALL than with B-cell ALL (P < .001 for all). Pulmonary opacity/infiltrate was associated with younger age (P = .003) and was more common in T-cell ALL than in B-cell ALL (P = .001). Peribronchial/perihilar thickening was associated with younger age (P < .001) and with positive central nervous system disease (P = .012). Patients with cardiomegaly were younger (P = .031), more often black than white (P = .007), and more often categorized as low risk than standard/high risk (P = .017). Patients with a mediastinal mass, pleural effusion/thickening, tracheal deviation/compression, or pulmonary opacity/infiltrate were more likely to receive less invasive sedation and more intensive care unit admissions and respiratory support (P ≤ .001 for all). Cardiomegaly was associated with intensive care unit admission (P = .008). No patients died of cardiorespiratory events during the initial 7 days of management.

Conclusions: The CXR can detect various intrathoracic lesions and is helpful in planning initial management.
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http://dx.doi.org/10.1016/j.jpeds.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388067PMC
August 2020

Expert consensus statements for Waldeyer's ring involvement in pediatric Hodgkin lymphoma: The staging, evaluation, and response criteria harmonization (SEARCH) for childhood, adolescent, and young adult Hodgkin lymphoma (CAYAHL) group.

Pediatr Blood Cancer 2020 09 16;67(9):e28361. Epub 2020 Jul 16.

Division of Haematology/Oncology, Department of Paediatrics, SickKids Hospital and University of Toronto, Toronto, Canada.

Waldeyer's ring (WR) involvement in pediatric Hodgkin lymphoma (HL) is extremely rare and criteria for determining involvement and response to treatment are unclear. The international Staging, Evaluation, and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) Group performed a systematic review of the literature in search of involvement or response criteria, or evidence to support specific criteria. Only 166 cases of HL with WR involvement were reported in the literature, 7 of which were pediatric. To date no standardized diagnostic or response assessment criteria are available. Given the paucity of evidence, using a modified Delphi survey technique, expert consensus statements were developed by the SEARCH group to allow for a more consistent definition of disease and response evaluation related to this rare site of involvement among pediatric oncologists. The available evidence and expert consensus statements are summarized.
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http://dx.doi.org/10.1002/pbc.28361DOI Listing
September 2020

Whole-joint magnetic resonance imaging to assess osteonecrosis in pediatric patients with acute lymphoblastic lymphoma.

Pediatr Blood Cancer 2020 08 30;67(8):e28336. Epub 2020 May 30.

Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Background: Osteonecrosis is a debilitating complication in children and adolescents with acute lymphoblastic leukemia or acute lymphoblastic lymphoma (LLy). An objective screening test to identify patients at risk for symptomatic, extensive joint involvement will help manage osteonecrosis.

Methods: We performed a prospective, longitudinal pilot study with whole-joint magnetic resonance imaging (MRI) of shoulders, elbows, hips, knees, ankles, and hindfeet to evaluate the incidence and timing of osteonecrosis involving multiple joints in 15 patients with LLy aged 9-21 years at diagnosis.

Results: Osteonecrosis affecting ≥30% of the epiphysis occurred in eight of 15 patients, with a high prevalence in hips (12 of 26 examined [46%]) and knees (10 of 26 [38%]) post reinduction I and in shoulders (seven of 20 [35%]) post reinduction II. Most osteonecrotic hips and knees with ≥30% epiphyseal involvement became symptomatic and/or underwent surgery (100% and 82%, respectively). All eight patients with ≥30% epiphyseal involvement had multijoint involvement. Seven of these patients had hip or knee osteonecrosis by the end of remission induction, and only these patients developed osteonecrosis that became symptomatic and/or underwent surgery in their hips, knees, shoulders, ankles, and/or feet; all of these joints were associated with epiphyseal abnormalities on post reinduction I imaging.

Conclusions: MRI screening in adolescent patients with LLy revealed osteonecrosis in multiple joints. Initial screening with hip and knee MRI at the end of induction may identify susceptible patients who could benefit from referrals to subspecialties, more extensive follow-up imaging of other joints, and early medical and surgical interventions.
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http://dx.doi.org/10.1002/pbc.28336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391358PMC
August 2020

Long-Term Functional Outcomes Among Childhood Survivors of Cancer Who Have a History of Osteonecrosis.

Phys Ther 2020 03;100(3):509-522

Department of Epidemiology and Cancer Control and Department of Pediatric Medicine, St Jude Children's Research Hospital.

Background: Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population.

Objective: The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls).

Design: This was a cross-sectional study.

Methods: This study included St Jude Lifetime Cohort Study participants who were ≥ 10 years from the diagnosis of childhood leukemia or lymphoma and ≥ 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL.

Results: Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed "Up & Go" Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m).

Limitations: Because some eligible survivors declined to participate, possible selection bias was a limitation of this study.

Conclusions: Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function.
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http://dx.doi.org/10.1093/ptj/pzz176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246066PMC
March 2020

Efficacy and Safety of Limited-Margin Conformal Radiation Therapy for Pediatric Rhabdomyosarcoma: Long-Term Results of a Phase 2 Study.

Int J Radiat Oncol Biol Phys 2020 05 25;107(1):172-180. Epub 2020 Jan 25.

Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address:

Purpose: Our purpose was to assess disease outcomes and late toxicities in pediatric patients with rhabdomyosarcoma treated with conformal photon radiation therapy (RT).

Methods And Materials: Sixty-eight patients (median age, 6.9 years) were treated with conformal photon RT to the primary site on a prospective clinical trial. Target volumes included a 1-cm expansion encompassing microscopic disease. Prescribed doses were 36 Gy to this target volume and 50.4 Gy to gross residual disease. Chemotherapy consisted of vincristine/dactinomycin (n = 6), vincristine/dactinomycin/cyclophosphamide (n = 37), or vincristine/dactinomycin/cyclophosphamide-based combinations (n = 25). Patients were evaluated with primary-site magnetic resonance imaging, whole-body [F]fluorodeoxyglucose positron emission tomography, and chest computed tomography for 5 years after treatment.

Results: Five-year disease-free survival was 88% for low-risk (n = 8), 76% for intermediate-risk (n = 37), and 36% for high-risk (n = 23) patients (P ≤ .01 for low risk/intermediate risk vs high risk). The cumulative incidence of local failure (LF) at 5 years for the entire cohort was 10.4%. Tumor size at diagnosis was a significant predictor of LF (P < .01). Patients with head and neck primary tumors (n = 31) had a 35% cumulative incidence of cataracts; the risk correlated with lens dose (P = .0025). Jaw dysfunction was more severe when the pterygoid and masseter muscles received a mean dose of >20 Gy (P = .013). Orbital hypoplasia developed more frequently after a mean bony orbit dose of >30 Gy (P = .041). Late toxicity in patients with genitourinary tumors included microscopic hematuria (9 of 14), bladder-wall thickening (10 of 14), and vaginal stenosis (2 of 5).

Conclusions: Long-term LF rates were low, and higher rates correlated with larger tumors. Treatment-related toxicities resulting in measurable functional deficits were not infrequent, despite the conformal RT approach.
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http://dx.doi.org/10.1016/j.ijrobp.2020.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668436PMC
May 2020

Clinical impact of post-induction resolution of pulmonary lesions in metastatic Ewing sarcoma.

Pediatr Blood Cancer 2020 04 15;67(4):e28150. Epub 2020 Jan 15.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Patients with metastatic Ewing sarcoma experience poor outcomes despite intensive systemic and local therapy. Early chemotherapy response of pulmonary metastases has been associated with prognosis in other pediatric malignancies. We reviewed the outcomes of patients with Ewing sarcoma and pulmonary metastases treated at our institution based on therapy received and early pulmonary response.

Materials And Methods: We retrospectively reviewed patients with newly diagnosed Ewing sarcoma and pulmonary metastases at St. Jude Children's Research Hospital between 1979 and 2015. Data obtained included demographic and treatment characteristics including chemotherapy, local control measures, whole lung irradiation (WLI) administration, autologous stem cell transplantation, and outcomes. Patients were evaluated for radiographic post-induction pulmonary complete response (CR). We estimated event-free survival (EFS) and overall survival (OS) and used Cox proportional hazards regression to examine the effects of clinical and treatment factors on outcomes.

Results: Fifty-four patients (median age, 12.9 years) were evaluated. Post-induction pulmonary CR was observed in 33 (61%) patients. WLI was delivered to 16 patients (4/33 with pulmonary CR and 12/21 with non-CR). At median 3.6 years follow-up, five-year EFS and OS were 30.8% ± 6.4% and 49.6% ± 7.1%, respectively. Post-induction pulmonary CR was associated with prolonged EFS (P < 0.001) but not improved OS (P = 0.065). Post-induction pulmonary CR was associated with a lower incidence of lung failure (P = 0.031).

Conclusions: Post-induction pulmonary CR is associated with improved EFS in patients with Ewing sarcoma who present with pulmonary metastases.
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http://dx.doi.org/10.1002/pbc.28150DOI Listing
April 2020

Definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma: A report from the International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH).

Pediatr Blood Cancer 2020 04 22;67(4):e28142. Epub 2019 Dec 22.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: The International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH) seeks to provide a universally acceptable definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma.

Procedure: A comprehensive literature search was performed using PubMed and Google Scholar with the search terms "Hodgkin lymphoma," "osseous lesions," "bony involvement," and "pediatric." Publications reviewed included case reports, retrospective analyses, and literature reviews. Each was evaluated for study design, number of participants, median age and age range at diagnosis, percentage of pediatric patients, criteria of interest definition, diagnostic tools, study objectives, and level of evidence. The final definition was based on the available data and consensus of the SEARCH working group.

Results: Twenty-five papers specifically addressing cortical bone involvement in Hodgkin lymphoma met the inclusion criteria. Eighteen papers were case reports with literature reviews; the remainder were observational cohort studies. Of these, 14 included pediatric patients (aged 0-21 years). The criteria for cortical bone involvement were not clearly defined in any paper, often varied within a study, and were inconsistent between publications.

Conclusions: The SEARCH group for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (CAYAHL) proposes the following criteria as defining cortical bone involvement: any cortical bone biopsy-proven lesion; a positive bony window lesion on computer tomography (CT), with an FDG-PET positive correlate in a patient with biopsy-proven Hodgkin lymphoma, if there is no other typical skeletal pathology; auspicious skeletal lesions on FDG-PET or magnetic resonance imaging should be confirmed by CT or Tc-99m scan to distinguish cortical lesions from bone marrow involvement. Nodal masses that extend into bone with bony destruction are considered extranodal extension or "E" lesions and do not represent metastatic or stage IV disease.
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http://dx.doi.org/10.1002/pbc.28142DOI Listing
April 2020

The association of mediastinal mass in the formation of thrombi in pediatric patients with non-lymphoblastic lymphomas.

Pediatr Blood Cancer 2020 02 17;67(2):e28057. Epub 2019 Nov 17.

Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Background: Children diagnosed with cancer are at a significantly higher risk of developing a thrombotic event (TE) compared with the general population. The rarity of these events makes it difficult to discern the specific risk factors; however, age, sex, presence of central venous lines, inherited thrombophilia, and mediastinal mass may play a role. The primary aim of this study is to identify prognostic characteristics of children diagnosed with non-lymphoblastic lymphomas associated with a greater risk of developing a TE early on in their disease, with an increased focus on mediastinal mass characteristics.

Methods: Retrospective chart review of pediatric patients diagnosed with non-lymphoblastic lymphoma between 2004 and 2014 at St. Jude Children's Research Hospital.

Results: TE occurred in 8.5% (n = 28/330) of individuals at a median of 21 days from the diagnosis of a non-lymphoblastic lymphoma, with 60% of TEs occurring within 30 days of diagnosis. Of the variables evaluated, only presence of a peripherally inserted central catheter (odds ratio [OR]: 3.14 [95% CI: 1.24-7.98; P = 0.02]) and degree of superior vena cava (SVC) compression of > 25% increased the odds of developing a TE (OR: 2.2 [95% CI: 1.01-4.93; P = 0.048]).

Conclusion: Pediatric patients with non-lymphoblastic lymphoma are at increased risk of developing TEs. In contrast to previous studies, the presence of a mediastinal mass alone was not associated with a higher risk of TE, but individuals with a mediastinal mass with 25% or greater degree of SVC compression were more likely to develop a TE. This finding highlights a high-risk group of children who may benefit from prophylactic anticoagulation.
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http://dx.doi.org/10.1002/pbc.28057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233458PMC
February 2020

Imaging of pediatric cutaneous melanoma.

Authors:
Sue C Kaste

Pediatr Radiol 2019 10 16;49(11):1476-1487. Epub 2019 Oct 16.

Departments of Diagnostic Imaging and Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MSN 220, Memphis, TN, 38105-3678, USA.

Melanoma accounts for 7% of all cancers in adolescents ages 15-19 years but is an unexpected malignancy in younger children. The prevalence of malignant melanoma is very rare in children ages 1-4 years, but certain non-modifiable risk factors such as xeroderma pigmentosum, congenital melanocytic nevus syndrome and other inherited traits increase the risk for its development in these young children. Recent genomic studies have identified characteristics of pediatric melanoma that differ from conventional melanoma seen in adults. In this review the authors inform on the types of melanoma seen in children and adolescents, discuss similarities and differences in melanoma between children and adults, and discuss the role of imaging in the care of these children.
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http://dx.doi.org/10.1007/s00247-019-04374-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986774PMC
October 2019

Brentuximab vedotin as consolidation after hematopoietic cell transplant for relapsed Hodgkin lymphoma in pediatric patients.

Pediatr Blood Cancer 2019 12 20;66(12):e27962. Epub 2019 Aug 20.

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.

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http://dx.doi.org/10.1002/pbc.27962DOI Listing
December 2019

Prediction of Low and Very Low Bone Mineral Density Among Adult Survivors of Childhood Cancer.

J Clin Oncol 2019 09 31;37(25):2217-2225. Epub 2019 May 31.

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

Purpose: To develop and validate prediction models for low and very low bone mineral density (BMD) on the basis of clinical and treatment characteristics that identify adult survivors of childhood cancer who require screening by dual-energy x-ray absorptiometry.

Patients And Methods: White survivors of childhood cancer (n = 2,032; median attained age, 29.3 years [range, 18.1 to 40.9 years]) enrolled in the St Jude Lifetime Cohort (SJLIFE; development) and survivors treated at the Erasmus Medical Center (validation) in the Netherlands (n = 403; median age, 24.2 years [range, 18.0 to 40.9 years]) were evaluated with dual-energy x-ray absorptiometry to determine lumbar spine BMD and total-body BMD. Low and very low BMD were defined as lumbar spine BMD and/or total-body BMD scores of -1 or lower or -2 or lower, respectively. Multivariable logistic regression was used to build prediction models; performance was assessed using receiver operating characteristic curves. Diagnostic values were calculated at different probabilities.

Results: Low BMD was present in 51% and 45% of SJLIFE and Dutch participants, respectively, and very low BMD was present in 20% and 10%, respectively. The model for low BMD included male sex (odds ratio [OR], 3.07), height (OR, 0.95), weight (OR, 0.98), attained age (OR, 0.97), current smoking status (OR, 1.48), and cranial irradiation (OR, 2.11). Areas under the curve were 0.72 (95% CI, 0.70 to 0.75) in the SJLIFE cohort and 0.69 (95% CI, 0.64 to 0.75) in the Dutch cohort. The sum of the sensitivity (69.0%) and specificity (64.0%) was maximal at the predicted probability of 50%. The model for very low BMD included male sex (OR, 3.28), height (OR, 0.95), weight (OR, 0.97), attained age (OR, 0.98), cranial irradiation (OR, 2.07), and abdominal irradiation (OR, 1.61), yielding areas under the curve of 0.76 (95% CI, 0.73 to 0.78; SJLIFE cohort) and 0.75 (95% CI, 0.67 to 0.83; Dutch cohort).

Conclusion: Validated prediction models for low and very low BMD, using easily measured patient and treatment characteristics, correctly identified BMD status in most white adult survivors through age 40 years.
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http://dx.doi.org/10.1200/JCO.18.01917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804829PMC
September 2019

Height-corrected low bone density associates with severe outcomes in sickle cell disease: SCCRIP cohort study results.

Blood Adv 2019 05;3(9):1476-1488

Department of Hematology.

Low bone mineral density (BMD) disproportionately affects people with sickle cell disease (SCD). Growth faltering is common in SCD, but most BMD studies in pediatric SCD cohorts fail to adjust for short stature. We examined low BMD prevalence in 6- to 18-year-olds enrolled in the Sickle Cell Clinical Research and Intervention Program (SCCRIP), an ongoing multicenter life span SCD cohort study initiated in 2014. We calculated areal BMD for chronological age and height-adjusted areal BMD (Ht-aBMD) scores for the SCCRIP cohort, using reference data from healthy African American children and adolescents enrolled in the Bone Mineral Density in Childhood Study. We defined low BMD as Ht-aBMD scores less than or equal to -2 and evaluated its associations with demographic and clinical characteristics by using logistic regression analyses. Of the 306 children and adolescents in our study cohort (mean age, 12.5 years; 50% female; 64% HbSS/Sβ0-thalassemia genotype; 99% African American), 31% had low areal BMD for chronological age scores and 18% had low Ht-aBMD scores. In multivariate analyses, low Ht-aBMD scores associated with adolescence (odds ratio [OR], 7.7; 95% confidence interval [CI], 1.94-30.20), hip osteonecrosis (OR, 4.0; 95% CI, 1.02-15.63), chronic pain (OR, 10.4; 95% CI, 1.51-71.24), and hemoglobin (OR, 0.74; 95% CI, 0.57-0.96). Despite adjusting for height, nearly 20% of this pediatric SCD cohort still had very low BMD. As the SCCRIP cohort matures, we plan to prospectively evaluate the longitudinal relationship between Ht-aBMD scores and markers of SCD severity and morbidity.
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http://dx.doi.org/10.1182/bloodadvances.2018026047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517655PMC
May 2019

Treatment patterns and disease outcomes for pediatric patients with refractory or recurrent Hodgkin lymphoma treated with curative-intent salvage radiotherapy.

Radiother Oncol 2019 05 5;134:89-95. Epub 2019 Feb 5.

Department of Radiation Oncology, St. Jude Children's Hospital, Memphis, United States.

Background And Purpose: The use of radiotherapy (RT) for pediatric patients with Hodgkin lymphoma (HL) experiencing disease progression or recurrence (15%) is controversial. We report treatment patterns and outcomes for pediatric patients with refractory/recurrent HL (rrHL) treated with curative-intent RT.

Materials And Methods: Forty-six patients with rrHL treated with salvage RT at our institution were identified. All received risk-adapted, response-based frontline therapy and were retrieved with cytoreductive regimens followed by RT to failure sites, with or without autologous hematopoietic cell transplantation (AHCT). Cumulative incidence (CIN) of local failure (LF) and survival were estimated after salvage RT and regression models determined predictors of LF after salvage RT.

Results: RT was administered as part of frontline therapy in 70% of patients, omitted for early response assessment in 13%, or deferred for primary progression in 17%. AHCT was omitted in 20% of patients. Median initial and salvage dose/site were 25.5 Gy and 30.6 Gy, respectively. Eight patients experienced progression. Two died without progression (median follow-up from salvage RT = 3.8 years). The 5-year CIN of LF after salvage RT was 17.7% (95% confidence interval [CI], 8.2-30.2%). The 5-year freedom from subsequent treatment failure and overall survival (OS) was 80.1% (95% CI, 69.2-92.6%) and 88.5% (95% CI, 79.5-98.6%), respectively. Inadequate response to salvage systemic therapy (p = 0.048) and male sex (p = 0.049) were significantly associated with LF after salvage RT.

Conclusion: rrHL is responsive to salvage RT, with low LF rates after moderate doses. OS is excellent, despite refractory disease. Initial salvage therapy response predicts subsequent LF.
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http://dx.doi.org/10.1016/j.radonc.2019.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478442PMC
May 2019

Bloodstream infections exacerbate incidence and severity of symptomatic glucocorticoid-induced osteonecrosis.

Pediatr Blood Cancer 2019 06 13;66(6):e27669. Epub 2019 Feb 13.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Osteonecrosis is a common toxicity associated with glucocorticoid (e.g., dexamethasone and prednisone) treatment of children with acute lymphoblastic leukemia (ALL), but risk factors are incompletely defined. Infections are also a common complication of ALL therapy. Lipopolysaccharide (LPS) is used experimentally to mimic infection-related systemic effects. To our knowledge, the contribution of systemic infections to the risk of glucocorticoid-induced osteonecrosis has not been investigated.

Procedure: Patients with ALL on St. Jude Total Therapy XV (n = 365) were assessed for documented bacteremia prior to development of osteonecrosis, which was confirmed by MRI, and graded using the National Cancer Institute's Common Terminology for Adverse Events (version 3.0). In a preclinical model, Balb/cJ mice treated with dexamethasone plus or minus LPS were assessed for frequency and severity of osteonecrosis and arteriopathy.

Results: We found that patients with ALL who experienced bacteremia had a higher frequency of symptomatic osteonecrosis (≥grade 2) than those who did not (OR: 1.88; 95% CI, 1.03-3.41, P = 0.038). LPS exacerbated experimental dexamethasone-induced osteonecrosis. Mice treated with dexamethasone plus LPS had a higher incidence of osteonecrosis (P = 0.00086) and arteriopathy (P = 0.0047) than did those treated with dexamethasone alone, and the severity of osteonecrosis (P = 0.00045) and arteriopathy (P = 0.0048) was also more pronounced with the addition of LPS treatment. The increase in osteonecrosis was not explained by any alteration of dexamethasone pharmacokinetics by LPS.

Conclusions: These data identify systemic infection during ALL therapy as a novel risk factor in the development of glucocorticoid-induced osteonecrosis.
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http://dx.doi.org/10.1002/pbc.27669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472979PMC
June 2019

Changes in body mass index, height, and weight in children during and after therapy for acute lymphoblastic leukemia.

Cancer 2018 11 25;124(21):4248-4259. Epub 2018 Oct 25.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Children with acute lymphoblastic leukemia (ALL) have an increased risk of obesity and short stature. To the authors' knowledge, data regarding patients treated on contemporary protocols without cranial irradiation are limited.

Methods: Changes in z scores for body mass index (BMI), height, and weight from the time of diagnosis to 5 years off therapy were evaluated using multivariable analysis in 372 children with ALL who were aged 2 to 18 years at the time of diagnosis and were enrolled on the St. Jude Children's Research Hospital Total XV protocol from 2000 through 2007.

Results: The percentage of overweight/obese patients increased from 25.5% at the time of diagnosis to approximately 50% during the off-therapy period. Median BMI z scores increased significantly during glucocorticoid therapy (induction: ∆0.56; 95% confidence interval [95% CI], 0.29-0.64 [P<.001]; and reinduction II: ∆0.22; 95% CI, 0.13-0.49 [P=.001]) and during the first year after therapy (∆0.18; 95% CI, 0.08-0.46 [P=.006]). Among patients who were of healthy weight/underweight at the time of diagnosis, those aged 2 to <10 years at diagnosis had a significantly higher risk of becoming overweight/obese during or after therapy compared with those aged ≥10 years (P=.001). Height z scores declined during treatment and improved after therapy. Being aged 2 to <10 years at the time of diagnosis, being of low-risk status, having a white blood cell count < 50×10 /L at the time of diagnosis, and having negative central nervous system disease were associated with significantly better improvements in z scores for height during the off-therapy period compared with being aged ≥10 years, being of standard-risk/high-risk status, having a white blood cell count  ≥ 50×10 /L, and having positive central nervous system disease, respectively.

Conclusions: The results of the current study demonstrate that obesity is prevalent, and height growth, especially in patients with identified risk factors, appears compromised. Multidisciplinary intervention should begin during induction therapy and continue during the off-therapy period.
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http://dx.doi.org/10.1002/cncr.31736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263845PMC
November 2018

Barry Davis Fletcher, MDCM (1935-2018).

Authors:
Sue C Kaste

Pediatr Radiol 2018 11;48(12):1823-1824

Department of Diagnostic Imaging, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MSN 220, Memphis, TN, 38105-3678, USA.

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http://dx.doi.org/10.1007/s00247-018-4262-1DOI Listing
November 2018

Vaso-occlusive crisis as a predictor of symptomatic avascular necrosis in children with sickle cell disease.

Pediatr Blood Cancer 2018 12 5;65(12):e27435. Epub 2018 Sep 5.

Janssen Research & Development, Raritan, New Jersey.

Avascular necrosis (AVN) is a chronic bone complication of sickle cell disease (SCD) resulting in significant morbidity. Understanding associated risk factors can facilitate risk-based screening, earlier identification, and prompt intervention. Between 1998 and 2014, 26 symptomatic cases with imaging evidence of AVN were compared 1:5 with age- and SCD genotype-matched controls (n = 128). Patients with 1-5 vaso-occlusive crisis (VOC) (OR 11.9, 95% CI, 1.4-99.9; P = 0.02) and more than 5 VOC (OR 53.6, 95% CI, 5.5-520.2; P = 0.0006) in a 5-year period were more likely to have AVN. Symptomatic patients with more than five VOC in 5 years may benefit from radiologic screening for AVN.
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http://dx.doi.org/10.1002/pbc.27435DOI Listing
December 2018

The role of routine imaging in pediatric cutaneous melanoma.

Pediatr Blood Cancer 2018 12 19;65(12):e27412. Epub 2018 Aug 19.

Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Background: Optimal imaging for children with pediatric malignant melanoma (MM) is unknown.

Methods: We reviewed clinical and imaging findings of patients with American Joint Commission on Cancer (AJCC) stage IIC-IV MM treated on our institutional MEL06 trial. All patients had baseline brain magnetic resonance imaging/computed tomography (MRI/CT), positron emission tomography/computed tomography (PET/CT), CT chest, abdomen, and pelvis (CTCAP). Patients on stratum A (PEG-interferon, where PEG is pegylated; AJCC IIC, IIIA, IIIB; n = 16) had imaging every 6 months; stratum B1 (PEG-interferon and temozolomide; unresectable measurable disease, metastatic, or recurrent; n = 2) had PET/CT scans every 2 months and brain imaging studies every 4 months; stratum B2 patients (PEG-interferon and temozolomide; unresectable nonmeasurable, metastatic, or recurrent, n = 3) had imaging every 4 months. Off-therapy imaging was done every 6 months for 3 years.

Results: There were 21 patients (11 females, 11 spitzoid, median age 14 years, head/neck [6], trunk [7], extremities [8]). Patients with spitzoid melanoma underwent 236 imaging studies in total (86 PET/CT, 81 CTCAP, 11 CT chest, 10 CT brain, 48 MRI brain) at a median cost per patient of $32,718. Thirteen studies (5.8%) had findings that led to two biopsies (one positive). For conventional MM, 162 studies (61 PET/CT, 57 CTCAP, 8 CT chest, 7 CT brain, and 29 MRI brain) were performed with a median cost per patient of $23,420. Twenty (14%) had findings leading to six biopsies (four positive). At 6.3 years (range 0.4-9.2), 17 patients remain disease-free.

Conclusion: Children with spitzoid melanoma require minimal imaging at diagnosis and follow-up. Patients with conventional MM should be imaged according to adult guidelines.
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http://dx.doi.org/10.1002/pbc.27412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193828PMC
December 2018

Risk factors for nonunion of bone fracture in pediatric patients: An inception cohort study of 237,033 fractures.

Medicine (Baltimore) 2018 Aug;97(31):e11691

Department of Orthopedic Surgery, Louisiana State University Health Science Center, New Orleans Departments of Radiology and Oncology, St. Jude Children's Research Hospital Department of Radiology, University of Tennessee School of Health Sciences, Memphis, Tennessee Department Orthopedic Surgery, Children's Hospital, New Orleans, Louisiana Department of Statistics, North Carolina State University, Raleigh, North Carolina.

Adult fracture nonunion risk is related to injury severity and surgical technique, yet nonunion is not fully explained by these risk factors alone; biological risk factors are also important. We test a hypothesis that risk factors associated with pediatric fracture nonunion are similar to adult nonunion risk factors.Inception cohort study in a large payer database of pediatric fracture patients (0-17 years) in the United States in calendar year 2011. Continuous enrollment in the database was required for 12 months, to allow time to capture a nonunion diagnosis. The final database collated demographic descriptors, treatment procedures as per Current Procedural Terminology (CPT) codes, comorbidities as per International Statistical Classification of Diseases and Related Health Problems (ICD-9) codes, and drug prescriptions as per National Drug Code Directory (Red Book) codes. Logistic regression was used to calculate odds ratios (ORs) for variables associated with nonunion.Among 237,033 pediatric fractures in 18 bones, the nonunion rate was 0.85%. Increased nonunion risk was associated with increasing age, male gender, high body-mass index, severe fracture (e.g., open fracture, multiple fractures), and tobacco smoking (all, P < .0001). Nonunion rate varied with fracture location; scaphoid, neck of femur, and tibia/fibula were most likely to go to nonunion. Nonunion ORs were significantly increased for risk factors including; surgical procedure, cardiovascular disease, Vitamin D deficiency, osteoarthritis, osteoporosis, and opioid prescription (all, multivariable P < .001).Nonunion is rare in pediatric patients, but nonunion risk increases with increasing age. We confirm a hypothesis that risk factors for pediatric nonunion are similar to adult nonunion risk factors. Scaphoid fractures in adolescents have nearly the same risk of nonunion as in adults. Opioids should be used cautiously in pediatric patients, as they are associated with a significant and substantial elevation of nonunion risk.

Level Of Evidence: Prognostic study, Retrospective, Level II.
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http://dx.doi.org/10.1097/MD.0000000000011691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081185PMC
August 2018

Influence of fitness on health status among survivors of acute lymphoblastic leukemia.

Pediatr Blood Cancer 2018 11 29;65(11):e27286. Epub 2018 Jul 29.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.

Introduction: We aimed to determine the prevalence of self-reported adverse health status among childhood acute lymphoblastic leukemia (ALL) survivors and to identify associations between components of physical fitness and health status.

Methods: Participants included 365 ALL survivors (mean age at evaluation of 28.6 ± 5.9 years) and 365 age-, sex-, and race-matched community controls. Self-report of poor general health, poor mental health, functional impairments, and activity limitations were used to describe adverse health status. Fitness was evaluated by assessing flexibility, muscular strength and endurance, peak oxygen uptake, and balance. Generalized linear models were used to examine associations between fitness metrics and health status.

Results: Survivors were more likely than controls to report poor general health (20.6% vs. 10.4%, risk ratio [RR] = 2.0, 95% confidence intervals [CI] = 1.4-2.9), poor mental health (28.0% vs. 14.5%, RR = 1.9, 95% CI = 1.4-2.6), functional impairments (10.5% vs. 4.1%, RR = 2.5, 95% CI = 1.4-4.6), and activity limitations (29.0% vs. 14.4%, RR = 2.0, 95% CI = 1.5-2.7). Survivors whose balance scores were more than 1.5 standard deviations below the mean of the control population were more likely to report poor general health (RR = 1.7, 95% CI = 1.1-2.8), poor mental health (RR = 1.9, 95% CI = 1.3-2.8), and functional limitations (RR = 2.5, 95% CI = 1.2-56). Survivors with low strength were more likely to report poor general health (RR = 1.8, 95% CI = 1.1-3.1), functional impairments (RR = 4.2, 95% CI = 1.7-10.4), and activity limitations (RR = 1.8, 95% CI = 1.2-2.8).

Conclusions: ALL survivors, particularly those with poor balance and reduced muscular strength, are at increased risk for adverse health status.
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http://dx.doi.org/10.1002/pbc.27286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150801PMC
November 2018

Serum Alanine Aminotransferase Elevations in Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort Study.

Hepatology 2019 01 25;69(1):94-106. Epub 2018 Dec 25.

Departments of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN.

The purpose of this study was to define the prevalence of and risk factors for elevated serum alanine aminotransferase (ALT) level among adult childhood cancer survivors (CCS). The study cohort comprised 2,751 CCS from the St. Jude Lifetime Cohort Study (>10 years postdiagnosis, age ≥18 years). Serum ALT level was graded using the Common Terminology Criteria for Adverse Events v. 4.03. Modified Poisson regression models were used to estimate relative risks and 95% confidence intervals for the association between demographic and clinical factors and grades 1-4 ALT on the selected models. A total of 1,339 (48.7%) CCS were female; 2,271 (82.6%) were non-Hispanic white. Median age at evaluation was 31.4 years (interquartile range [IQR] = 25.8-37.8); median elapsed time from diagnosis to evaluation was 23.2 years (IQR = 17.6-29.7). A total of 1,137 (41.3%) CSS had ALT > upper limit of normal (Common Terminology Criteria for Adverse Events v. 4.03 grade 1-1,058 (38.5%); grade 2-56 (2.0%); grade 3-23 (0.8%); grade 4-none). Multivariable models demonstrated non-Hispanic white race/ethnicity, age at evaluation in years, being overweight or obese, presence of the metabolic syndrome, current treatment with atorvastatin or rosuvastatin or simvastatin, hepatitis C virus infection, prior treatment with busulfan or thioguanine, history of hepatic surgery, and the percentage of liver treated with ≥10 Gray, ≥15 Gray, or ≥20 Gray were associated with elevated ALT. Conclusion: Grade 3 or 4 hepatic injury is infrequent in CCS. Mild hepatic injury in this group may be amenable to lifestyle modifications.
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http://dx.doi.org/10.1002/hep.30176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324960PMC
January 2019

Sickle Cell Clinical Research and Intervention Program (SCCRIP): A lifespan cohort study for sickle cell disease progression from the pediatric stage into adulthood.

Pediatr Blood Cancer 2018 09 24;65(9):e27228. Epub 2018 May 24.

School of Public Health, University of Memphis, Memphis, Tennessee.

Background: Previous natural history studies have advanced the understanding of sickle cell disease (SCD), but generally have not included sufficient lifespan data or investigation of the role of genetics in clinical outcomes, and have often occurred before the widespread use of disease-modifying therapies, such as hydroxyurea and chronic erythrocyte transfusions. To further advance knowledge of SCD, St. Jude Children's Research Hospital established the Sickle Cell Clinical Research and Intervention Program (SCCRIP), to conduct research in a clinically evaluated cohort of individuals with SCD across their lifetime.

Procedures: Initiated in 2014, the SCCRIP study prospectively recruits patients diagnosed with SCD and includes retrospective and longitudinal collection of clinical, neurocognitive, geospatial, psychosocial, and health outcomes data. Biological samples are banked for future genomics and proteomics studies. The organizational structure of SCCRIP is based upon organ/system-specific working groups and is opened to the research community for partnerships.

Results: As of August 2017, 1,044 (92.3% of eligible) patients with SCD have enrolled in the study (860 children and 184 adults), with 11,915 person-years of observation. Population demographics included mean age at last visit of 11.3 years (range 0.7-30.1), 49.8% females, 57.7% treated with hydroxyurea, 8.5% treated with monthly transfusions, and 62.9% hemoglobin (Hb) SS or HbSB -thalassemia, 25.7% HbSC, 8.4% HbsB -Thalassemia, 1.7% HbS/HPFH, and 1.2% other.

Conclusions: The SCCRIP cohort will provide a rich resource for the conduct of high impact multidisciplinary research in SCD.
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http://dx.doi.org/10.1002/pbc.27228DOI Listing
September 2018

Factors influencing risk-based care of the childhood cancer survivor in the 21st century.

CA Cancer J Clin 2018 03 29;68(2):133-152. Epub 2018 Jan 29.

Member, Department of Oncology and Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN.

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society.
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http://dx.doi.org/10.3322/caac.21445DOI Listing
March 2018