Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma

BackgroundAnaplastic large cell lymphoma (ALCL) constitutes 10-15% of childhood non-Hodgkin lymphoma. EFS is 70% and currently 80% with the additional of targeted agents such as CD30 directed conjugated monoclonal antibody brentuximab or ALK inhibitors such as crizotinib. Expression of CD3, a T-cell...

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Main Authors: Ahmed Salah, Hanafy Hafez, Samah Semary, Eman Naguib Khorshed, Sonia Soliman, Iman Zaky, Shahenda M. Shahin, Leslie Lehmann, Alaa ElHaddad
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1569370/full
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author Ahmed Salah
Hanafy Hafez
Hanafy Hafez
Samah Semary
Samah Semary
Eman Naguib Khorshed
Eman Naguib Khorshed
Sonia Soliman
Sonia Soliman
Iman Zaky
Iman Zaky
Shahenda M. Shahin
Leslie Lehmann
Alaa ElHaddad
Alaa ElHaddad
author_facet Ahmed Salah
Hanafy Hafez
Hanafy Hafez
Samah Semary
Samah Semary
Eman Naguib Khorshed
Eman Naguib Khorshed
Sonia Soliman
Sonia Soliman
Iman Zaky
Iman Zaky
Shahenda M. Shahin
Leslie Lehmann
Alaa ElHaddad
Alaa ElHaddad
author_sort Ahmed Salah
collection DOAJ
description BackgroundAnaplastic large cell lymphoma (ALCL) constitutes 10-15% of childhood non-Hodgkin lymphoma. EFS is 70% and currently 80% with the additional of targeted agents such as CD30 directed conjugated monoclonal antibody brentuximab or ALK inhibitors such as crizotinib. Expression of CD3, a T-cell marker, can be lost or diminished in some ALCL cases. The literature is conflicting on whether CD3 expression affects prognosis, and it has been analyzed mostly in the relapse setting. The purpose of this study was to determine the effect of CD3 expression on survival and its relation to the other prognostic variables in newly diagnosed patients with pediatric ALCL treated at a single large pediatric oncology center.MethodsA retrospective study was done on 89 newly diagnosed pediatric ALCL patients (under 18 years old) treated at Children’s Cancer Hospital Egypt (CCHE-57357) from July 2007 to December 2019. Immunohistochemistry was utilized to confirm the diagnosis and determine CD3 expression in tumor cells. The impact of CD3 expression on event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS)) was analyzed.ResultsThe median age was 10.7 years with male to female ratio 1.8:1. The majority of patients (85.4%) were ALK positive. CD3 was positive in 31 (34.8%) of patients. The median follow-up period was 60 months. The five-year OS, EFS, and RFS rates for the entire group were 84.3%, 73.1%, and 81.5%, respectively. CD3 positivity was associated with a higher incidence of CNS involvement (p=0.03) but did not significantly impact other patient outcomes (EFS, RFS and OS). However, stage, B symptoms, and skin involvement were linked to a shorter relapse-free survival.ConclusionThis study indicates that CD3 expression may not be a major factor predicting survival in newly diagnosed pediatric ALCL. Additional research is needed to understand its association with CNS positive disease.
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spelling doaj-art-75c8091d1bf048c3beb1bc5f9db06a7e2025-08-20T03:25:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15693701569370Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphomaAhmed Salah0Hanafy Hafez1Hanafy Hafez2Samah Semary3Samah Semary4Eman Naguib Khorshed5Eman Naguib Khorshed6Sonia Soliman7Sonia Soliman8Iman Zaky9Iman Zaky10Shahenda M. Shahin11Leslie Lehmann12Alaa ElHaddad13Alaa ElHaddad14Department of Pediatric Oncology, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Pediatric Oncology, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Pediatric Oncology, National Cancer Institute, Cairo, EgyptDepartment of Pediatric Oncology, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Clinical Oncology, Faculty of Medicine, Beni-Suef University, Beni-Suef, EgyptDepartment of Surgical Pathology, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Surgical Pathology, National Cancer Institute (NCI), Cairo University, Cairo, EgyptDepartment of Clinical Pathology, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo, EgyptDepartment of Radio-diagnosis, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo, EgyptDepartment of Clinical Research, Children’s Cancer Hospital (57357), Cairo, Egypt0Department of Pediatric Oncology, Dana- Farber Cancer Institute, Boston, MA, United StatesDepartment of Pediatric Oncology, Children’s Cancer Hospital (57357), Cairo, EgyptDepartment of Pediatric Oncology, National Cancer Institute, Cairo, EgyptBackgroundAnaplastic large cell lymphoma (ALCL) constitutes 10-15% of childhood non-Hodgkin lymphoma. EFS is 70% and currently 80% with the additional of targeted agents such as CD30 directed conjugated monoclonal antibody brentuximab or ALK inhibitors such as crizotinib. Expression of CD3, a T-cell marker, can be lost or diminished in some ALCL cases. The literature is conflicting on whether CD3 expression affects prognosis, and it has been analyzed mostly in the relapse setting. The purpose of this study was to determine the effect of CD3 expression on survival and its relation to the other prognostic variables in newly diagnosed patients with pediatric ALCL treated at a single large pediatric oncology center.MethodsA retrospective study was done on 89 newly diagnosed pediatric ALCL patients (under 18 years old) treated at Children’s Cancer Hospital Egypt (CCHE-57357) from July 2007 to December 2019. Immunohistochemistry was utilized to confirm the diagnosis and determine CD3 expression in tumor cells. The impact of CD3 expression on event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS)) was analyzed.ResultsThe median age was 10.7 years with male to female ratio 1.8:1. The majority of patients (85.4%) were ALK positive. CD3 was positive in 31 (34.8%) of patients. The median follow-up period was 60 months. The five-year OS, EFS, and RFS rates for the entire group were 84.3%, 73.1%, and 81.5%, respectively. CD3 positivity was associated with a higher incidence of CNS involvement (p=0.03) but did not significantly impact other patient outcomes (EFS, RFS and OS). However, stage, B symptoms, and skin involvement were linked to a shorter relapse-free survival.ConclusionThis study indicates that CD3 expression may not be a major factor predicting survival in newly diagnosed pediatric ALCL. Additional research is needed to understand its association with CNS positive disease.https://www.frontiersin.org/articles/10.3389/fonc.2025.1569370/fullCD3survivalpediatric anaplastic large cell lymphomaALKoutcome
spellingShingle Ahmed Salah
Hanafy Hafez
Hanafy Hafez
Samah Semary
Samah Semary
Eman Naguib Khorshed
Eman Naguib Khorshed
Sonia Soliman
Sonia Soliman
Iman Zaky
Iman Zaky
Shahenda M. Shahin
Leslie Lehmann
Alaa ElHaddad
Alaa ElHaddad
Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma
Frontiers in Oncology
CD3
survival
pediatric anaplastic large cell lymphoma
ALK
outcome
title Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma
title_full Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma
title_fullStr Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma
title_full_unstemmed Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma
title_short Impact of CD3 expression on outcome in pediatric anaplastic large cell lymphoma
title_sort impact of cd3 expression on outcome in pediatric anaplastic large cell lymphoma
topic CD3
survival
pediatric anaplastic large cell lymphoma
ALK
outcome
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1569370/full
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