Publications by authors named "Emi H Caywood"

7 Publications

  • Page 1 of 1

Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies.

Blood 2020 04;135(15):1287-1298

CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.

Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) evaluated the immune profiles in chronic GVHD (cGVHD) and late acute GVHD (L-aGVHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .05, and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGVHD by the adjudication committee (non-NIH-CC) had immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1- and a decrease in PD-1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGVHD/L-aGVHD to L-aGVHD, with the most complex pattern in cGVHD. Comprehensive immune profiling will allow us to better understand how to minimize L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.
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http://dx.doi.org/10.1182/blood.2019003186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146024PMC
April 2020

Benefits and challenges with diagnosing chronic and late acute GVHD in children using the NIH consensus criteria.

Blood 2019 07 1;134(3):304-316. Epub 2019 May 1.

British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

Chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (L-aGVHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGVHD and to better classify graft-versus-host disease (GVHD) syndromes but have not been validated in patients <18 years of age. The objectives of this prospective multi-institution study were to determine: (1) whether the NIH-CC could be used to diagnose pediatric cGVHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGVHD and L-aGVHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGVHD and L-aGVHD using the NIH-CC. Twenty-seven transplant centers enrolled 302 patients <18 years of age before conditioning and prospectively followed them for 1 year posttransplant for development of cGVHD. Centers justified their cGVHD diagnosis according to the NIH-CC using central review and a study adjudication committee. A total of 28.2% of reported cGVHD cases was reclassified, usually as L-aGVHD, following study committee review. Similar incidence of cGVHD and L-aGVHD was found (21% and 24.7%, respectively). The most common organs involved with diagnostic or distinctive manifestations of cGVHD in children include the mouth, skin, eyes, and lungs. Importantly, the 2014 NIH-CC for bronchiolitis obliterans syndrome perform poorly in children. Past acute GVHD and peripheral blood grafts are major risk factors for cGVHD and L-aGVHD, with recipients ≥12 years of age being at risk for cGVHD. Applying the NIH-CC in pediatrics is feasible and reliable; however, further refinement of the criteria specifically for children is needed.
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http://dx.doi.org/10.1182/blood.2019000216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911839PMC
July 2019

RHEGMATOGENOUS RETINAL DETACHMENT AFTER INTRAARTERIAL CHEMOTHERAPY FOR RETINOBLASTOMA: The 2016 Founders Award Lecture.

Retina 2017 Aug;37(8):1441-1450

*Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; †The Retina Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; ‡The Nemours Center for Cancer and Blood Disorders, Nemours/Alfred I. DuPont Hospital for Children, Thomas Jefferson University, Wilmington, Delaware; and Departments of §Neurovascular and Endovascular Surgery, and ¶Neurological Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To evaluate rhegmatogenous retinal detachment (RRD) in eyes with retinoblastoma after intraarterial chemotherapy (IAC).

Design: Retrospective case series.

Methods: Chart review.

Main Outcome Measure: Development of RRD in the IAC era.

Results: Of 167 eyes in 157 consecutive patients, mean patient age at diagnosis of retinoblastoma was 19 months. Intraarterial chemotherapy was primary (75/167, 45%) or secondary (92/167, 55%). There were 10 eyes (10/167, 6%) that developed RRD after IAC. The RRD was mostly related to rapid tumor regression with atrophic retinal hole, occurring within one month (n = 8) or 12 months (n = 2) of IAC. Rhegmatogenous retinal detachment was found after primary (6/75, 8%) or secondary (4/92, 4%) IAC. Of primary cases, RRD was found in Group D (1/38 [3%], P = 0.1075) or Group E (5/30 [17%], P = 0.0348). For primary IAC (n = 75 eyes), RRD was found in endophytic (5/22 [23%], P = 0.0073), exophytic (0/29 [0%], P = 0.0760), or combined endophytic/exophytic pattern (1/24 [4%], P = 0.6575). A comparison of eyes with RRD (n = 10) versus without RRD (n = 157) found significant differences including greater mean age at presentation (38 vs. 18 months, P = 0.0522), greater 4-quadrant vitreous seeding (5/10, 50% vs. 27/157, 17%, P = 0.0236), and absence of subretinal fluid (3/10, 30% vs. 102/157, 65%, P = 0.0236). The cause of RRD was tumor regression-related atrophic retinal hole(s) in 7 (7/10, 70%) (unifocal [1/10, 10%] or multifocal [6/10, 60%] holes), cryotherapy-induced single atrophic hole in 2 (2/10, 20%), and single flap-tear from posterior vitreous detachment in one (1/10, 10%). In 4 (4/10, 40%) eyes with RRD, proliferative vitreoretinopathy was noted. The RRD was not related to intravitreal injection in any case, as in primary IAC no case had previous injection and in secondary IAC the injections were performed many months previously. Primary RRD repair involved pars plana vitrectomy in three, scleral buckle without drainage in one, laser barricade in one, and observation in five eyes. After 24 months mean follow-up, the retina showed complete reattachment (3/10, 30%), partial reattachment (2/10, 20%), and persistent detachment in all observed eyes (5/10, 50%). Enucleation was necessary for tumor recurrence (4/10, 40%) or neovascular glaucoma (1/10, 10%). There were no tumor-related metastases or death.

Conclusion: After IAC for retinoblastoma, RRD occurs in 6%, mostly in advanced eyes with extensive endophytic tumor and generally from atrophic retinal hole after rapid tumor regression.
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http://dx.doi.org/10.1097/IAE.0000000000001382DOI Listing
August 2017

Challenges in Converting Acute Myeloid Leukemia (AML) Genomics Into AML Clinical Trials.

J Clin Oncol 2015 Dec 16;33(36):4238-9. Epub 2015 Nov 16.

Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE

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http://dx.doi.org/10.1200/JCO.2015.63.9252DOI Listing
December 2015

Prognostic factors of childhood and adolescent acute myeloid leukemia (AML) survival: evidence from four decades of US population data.

Cancer Epidemiol 2015 Oct 6;39(5):720-6. Epub 2015 Jul 6.

Department of Hematology/Oncology, A I duPont Hospital for Children, Wilmington, DE 19803, United States.

Growing insight into prognosis of pediatric acute myeloid leukemia (AML) survival has led to improved outcome over time and could be further enhanced through investigation using a large number of patients. To characterize the extent of the association of pediatric AML survival with its identified prognostic factors, we analyzed the United States population-based Surveillance Epidemiology and End Results (SEER) large dataset of 3442 pediatric AML patients diagnosed and followed between 1973 and 2011 using a Cox proportional hazards model stratified by year of diagnosis. Patients diagnosed between 10 and 19 years of age were at a higher risk of death compared to those diagnosed before age 10 (adjusted hazard ratio (aHR): 1.30, 95% confidence interval (CI): 1.17-1.44). African Americans (1.27, 1.09-1.48) and Hispanics (1.15, 1.00-1.32) had an elevated risk of mortality than Caucasians. Compared to the subtype acute promyelocytic leukemia, AML with minimal differentiation (2.44, 1.78-3.35); acute erythroid leukemia (2.34, 1.60-3.40); AML without maturation (1.87, 1.35-2.59); and most other AML subtypes had a higher risk of mortality, whereas AML with inv(16) had a substantially lower risk. Age at diagnosis, race-ethnicity, AML subtype, county level poverty and geographic region appeared as significant prognostic factors of pediatric AML survival in the US. Contrary to previous findings, the subtypes of AML with t(9;11)(p22;q23)MLLT3-MLL, AML without maturation and acute myelomonocytic leukemia emerged to be indicative of poor outcome.
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http://dx.doi.org/10.1016/j.canep.2015.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398442PMC
October 2015

Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy.

Curr Opin Ophthalmol 2014 Sep;25(5):374-85

aOcular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA bDivision of Oncology, Children's Hospital of Philadelphia, Philidelphia, PA, USA cDepartment of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA dNemours Center for Cancer and Blood Disorders (EHC), Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, USA.

Purpose Of Review: The management of retinoblastoma is complex and involves strategically chosen methods of enucleation, radiotherapy, chemotherapy, laser photocoagulation, thermotherapy, and cryotherapy. Chemotherapy has become the most common eye-sparing modality. There are four routes of delivery of chemotherapy for retinoblastoma, including intravenous, intra-arterial, periocular, and intravitreal techniques. The purpose of this review is to discuss the current rationale for each method and the anticipated outcomes.

Recent Findings: The diagnosis of retinoblastoma should be clinically established prior to embarking on a chemotherapy protocol. There are over 25 conditions that can closely simulate retinoblastoma in a young child. In addition, enucleation is an acceptable method for management, particularly with advanced retinoblastoma. Intravenous chemotherapy is generally used for germline mutation (bilateral, familial) retinoblastoma with excellent tumor control for groups A, B, and C and intermediate control for group D eyes. Intra-arterial chemotherapy is used as primary therapy in selected cases for nongermline mutation (unilateral) retinoblastoma with excellent control, and also used as secondary therapy for recurrent solid retinoblastoma, subretinal seeds, and vitreous seeds. Periocular chemotherapy is employed to boost local chemotherapy dose in advanced bilateral groups D and E eyes or for localized recurrences. Intravitreal chemotherapy is used for recurrent vitreous seeds from retinoblastoma. Patients at high risk for metastases should receive intravenous chemotherapy.

Summary: Chemotherapy is effective for retinoblastoma and the targeted treatment route depends on the clinical features and anticipated outcomes.
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http://dx.doi.org/10.1097/ICU.0000000000000091DOI Listing
September 2014

Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma.

Ophthalmology 2014 Jul 21;121(7):1453-60. Epub 2014 Mar 21.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Objective: To analyze our 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy.

Design: Retrospective interventional case series.

Participants: A total of 70 eyes of 67 patients.

Intervention: Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary.

Main Outcome Measures: Tumor control and treatment complications.

Results: The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1-7 sessions). After IAC with a mean follow-up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). More lasting complications included vitreous hemorrhage (2%), branch retinal artery obstruction (1%), ophthalmic artery spasm with reperfusion (2%), ophthalmic artery obstruction (2%), partial choroidal ischemia (2%), and optic neuropathy (<1%). Over the past 3 years, the combined incidence of ophthalmic, retinal, and choroidal vascular ischemia was reduced to 1%. There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death.

Conclusions: Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.
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http://dx.doi.org/10.1016/j.ophtha.2014.01.026DOI Listing
July 2014