Outcome of children and adolescents with lymphoblastic lymphoma

ORIGINAL ARTICLE Outcome of children and adolescents with lymphoblastic lymphoma Outcome of children and adolescents with lymphoblastic lymphoma Maria Christina Lopes Araújo Oliveira1*, Keyla Christy Sampaio2, Aline Carneiro Oliveira3, Aieska Dantas Santos4, Lúcia Porto Castro5, Marcos Borato Viana6 PhD – Associate Professor, Department of Pediatrics, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil 1 PhD – Adjunct Professor – Department of Pediatrics, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil 2 Physician, Hospital das Clínicas, UFMG, Belo Horizonte, MG, Brazil 3 Physician, HC-UFMG, Belo Horizonte, MG, Brazil 4 5 MSc – Assistant Professor, Pathology Department, UFMG, Belo Horizonte, MG, Brazil 6 PhD – Full Professor, Pediatrics Department, UFMG, Belo Horizonte, MG, Brazil Summary Study conducted at Pediatrics Department, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG Brazil Article received: 1/19/2015 Accepted for publication: 5/4/2015 *Correspondence: Address: Av. Professor Alfredo Balena, 100 Belo Horizonte, MG – Brazil Postal code: 30130100 http://dx.doi.org/10.1590/1806-9282.62.01.59 Financial support: CAPES Introduction: lymphoblastic lymphoma (LBL) is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or less with LBL admitted between January 1981 and December 2013. Patients received intensive chemotherapy regimen derived from acute lymphoblastic leukemia (ALL) therapy. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.613.8). LBL had T cell origin in 16 patients (59%). The most common primary manifestation in T-cell LBL was mediastinum involvement in 9 patients (56%). Intra-abdominal tumor was the major site of involvement in patients with pBLBL. Most patients had advanced disease (18 patients – 67%) at diagnosis. Twenty-four patients (89%) achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95), 22 patients (81%) were alive in first complete remission. Five children (18.5%) died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4). Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy. Keywords: precursor cell lymphoblastic leukemia-lymphoma, lymphoma, non-Hodgkin, pediatrics, survival. Introduction Lymphoblastic lymphomas (LBL) are lymphoid malignancies from immature or precursor cells representing one third of the cases of non-Hodgkin lymphoma (NHL) in children and adolescents.1-3 The current World Health Organization (WHO) classification assigns tumours of hematopoietic and lymphoid tissues in T lymphoblastic leukemia/lymphoma and B lymphoblastic leukemia/ lymphoma.4,5 Of note, only approximately 10% of LBL express B-cell markers in contrast to approximately 85% of Rev Assoc Med Bras 2016; 62(1):59-64 acute lymphoblastic leukemia (ALL).6 The distinction between leukemia and lymphoma is arbitrary and based on the extent of involvement of bone marrow (BM). It is usual to diagnose patients with ≥ 25% lymphoblasts in BM as having ALL, whereas patients with extra-medullary disease and less than 25% blasts in BM are diagnosed as LBL.7,8 Clinical presentation varies according to immunophenotype. T-cell lymphoblastic lymphomas (T-LBL) most commonly involve the anterior mediastinum and supradiaphragmatic lymph nodes.2,9 Pre-B lymphoblastic lym- 59 Oliveira MCLA et al. phomas (pB-LBL) are usually localized in peripheral lymph nodes and extranodal sites, such as skin, soft tissues, and bone, with a preference for the head and neck regions.10,11 Whether LBL and ALL in childhood are biologically identical or rather distinct disorders is not entirely clear.12,13 To date, the pathogenesis and genetic changes of LBL is poorly understood.3 LBLs are most effectively treated using ALL-based therapies.14 Nowadays, event-free survival (EFS) can be reached by 75-90% of children and adolescents.3,15,16 The objective of this study was to contribute to the knowledge of the clinical course and treatment outcome of 27 children and adolescents with LBL followed up at a single tertiary center. Methods This is a longitudinal retrospective observational cohort study that evaluated 27 children and adolescents aged 16 years or less with LBL. The patients were admitted to the Pediatric Hematology Unit, University Hospital, Universidade Federal de Minas Gerais (UFMG), between January 1981 and December 2013. Seven patients were excluded from the Kaplan-Meier survival analysis (see statistical session) because of previous treatment at other institutions (n=3), severe concomitant immunodeficiency (one with primary and two with secondary immunodeficiency), and one with bone marrow involvement with atypical cells that were not considered lymphoblasts. Medical records were reviewed to collect demographic data (age, gender), clinical data (medical history, physical examination, clinical presentation), diagnostic procedures (imaging studies, bone marrow aspiration, cerebrospinal fluid [CSF] analysis), staging, laboratory data (lactate dehydrogenase [LDH] levels, blood counts, serum electrolytes, liver and kidney tests), treatment, and outcome. Diagnosis was made by incisional or excisional biopsy, or cytological examination of pleural or abdominal effusions. Karyotype studies were not available at the time. All the diagnoses were confirmed by morphological and immunohistochemistry criteria defined by the World Health Organization (WHO) classification.17 Immunohistochemistry was performed using monoclonal antibodies CD20, CD10, CD79a, CD30, CD3, CD15, TdT, CD45, and CD45RO for the detection of B and T cells. Cell lineage assignment required 50% or more of positive neoplastic B or T cells. Pleural or abdominal effusions were examined by flow cytometry. Clinical staging was based on the St. Jude Children’s Research Hospital staging system.18 Central nervous system (CNS) disease was diagnosed by the presence of morphologically identifiable lymphoma cells (regardless of quantity) in CSF, an intracranial mass or cranial nerve palsy not caused by an extradural mass. Treatment Patients with LBL were treated according to protocols based on an ALL-type strategy. Patients admitted between 1981 and 1987 were treated according to the modified LSA2L2 protocol of the Memorial Sloan-Kettering Cancer Center.19 After 1987, patients were treated with a BFM83-based protocol (Berlin-Frankfur (...truncated)