Burkitt-like lymphoma with 11q aberration: A germinal center derived lymphoma genetically unrelated to Burkitt lymphoma

Burkitt-like lymphoma with 11q aberration is characterized by pathological features and gene expression profile resembling Burkitt lymphoma but lack MYC rearrangement and carries an 11q-arm aberration with proximal gains and telomeric losses. Whether these lymphomas are a distinct category or a particular variant of other recognized entities is controversial. To improve the understanding of Burkitt-like lymphoma with 11q aberration we have performed an analysis of copy number alterations and targeted sequencing of a large panel of B-cell lymphoma related genes in 11 cases. Most patients had localized nodal disease and a favourable outcome after therapy. Histologically, they were high grade B-cell lymphoma, not otherwise specified (8 cases), diffuse large B-cell lymphoma (2 cases) and only one was considered as atypical Burkitt lymphoma. All cases had a germinal center B-cell signature and phenotype with frequent LMO2 expression. Burkitt-like lymphoma with 11q aberration had frequent gains of 12q12-q21.1 and losses of 6q12.1-q21, and lacked common Burkitt lymphoma or diffuse large B-cell lymphoma alterations. Potential driver mutations were found in 27 genes, particularly involving BTG2, DDX3X, ETS1, EP300, and GNA13. However, ID3, TCF3, or CCND3 mutations were absent in all cases. These results suggest that Burkitt-like lymphoma with 11q aberration is a germinal center derived lymphoma closer to high grade B-cell lymphoma or diffuse large B-cell lymphoma rather than Burkitt lymphoma.Copyright © 2019, Ferrata Storti Foundation

Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report

<p>Abstract</p> <p>Background</p> <p><it>Fusarium </it>spp. is being isolated with increasing frequency as a pathogen in oncohematologic patients. Caspofungin and amphotericin B have been reported to have synergistic activity against <it>Fusarium </it>spp.</p> <p>Case presentation</p> <p>We herein report a case of disseminated fusariosis diagnosed by chest CT scan and positive blood cultures to <it>Fusarium </it>spp. Because the patient's clinical condition deteriorated, CRP levels increased, and blood cultures continued to yield <it>Fusarium </it>spp. despite liposomal amphotericin B monotherapy up to 5 mg/kg daily, treatment with caspofungin was added. Within 2 weeks of onset of combined antifungal therapy, the chest CT scan demonstrated a progressive resolution of the pulmonary lesions. Upon discontinuation of intravenous antifungals, the patient received suppressive therapy with oral voriconazole. Three months later, a chest CT scan showed no abnormalities. Twenty-five months after discontinuation of all antifungal therapy, the patient remains in complete remission of her neoplastic disease with no signs of clinical activity of the <it>Fusarium </it>infection.</p> <p>Conclusion</p> <p>This is the first description of successful treatment of disseminated fusariosis in a pediatric patient with acute lymphoblastic leukemia with caspofungin and amphotericin B followed by oral suppressive therapy with voriconazole.</p

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet)

IntroductionStudies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses.MethodsWe compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51).ResultsPatients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS.DiscussionThese results support the role of haploidentical donor SCT in children with ALL in CR2

Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia

The efficacy of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) patients has significantly increased in the last twenty years; as a result, the focus of research is slowly shifting from trying to increase survival rates to reduce chemotherapy-related toxicity.At the present time, the cornerstone of therapy for ALL is still formed by a reduced number of drugs with a highly toxic profile. In recent years, a number of genetic polymorphisms have been identified that can play a significant role in modifying the pharmacokinetics and pharmacodynamics of these drugs. The best example is that of the TPMT gene, whose genotyping is being incorporated to clinical practice in order to individualize doses of mercaptopurine. However, there are additional genes that are relevant for the metabolism, activity and/or transport of other chemotherapy drugs that are widely use in ALL, such as methotrexate, cyclophosphamide, vincristine, L-asparaginase, etoposide, cytarabine or cytotoxic antibiotics. These genes can also be affected by genetic alterations that could therefore have clinical consequences.In this review we will discuss recent data on this field, with special focus on those polymorphisms that could be used in clinical practice to tailor chemotherapy for ALL in order to reduce the occurrence of serious adverse effects

Adolescent cancer care: What has changed in Spain in the past decade?

Introduction and objective: In 2012, the Adolescents with Cancer working group published the results of a survey on care delivery for the adolescent population in Spain as a starting point for future intervention. The aim of this nationwide survey was to outline the current situation and assess whether the implemented strategies have resulted in changes in care delivery.Material and methods: Survey consisting of the same items analysed and published in 2012. The questionnaire was structured into sections devoted to epidemiology, psychosocial care, infrastructure, treatment and follow-up of adolescents with cancer. It was submitted to all hospitals in Spain with a paediatric haematology and oncology unit. We conducted a descriptive analysis of the results.Results: The percentage of patients aged up to 18 years managed in paediatric units has increa-sed from 35.9% to 77.5% in the past decade. The proportion of malignant blood tumours treated in paediatric units increased from 31% to 52%, and the proportion of solid tumours from 49% to 85%. In 2012, 30 units (out of 39) reported that new cases in adolescents amounted to up to 10% of the total. At present, only 14 (out of 40) continue to report this percentage. A decade ago, there were no specific adolescent cancer units in Spain. Now, 7 centres (out of 40) have specific multidisciplinary units. There has been little change in psychological support services for adolescents. The follow-up of survivors is carried out by paediatric specialists in 82.5% of the hospitals.Conclusions: The efforts made to centralise the care of adolescents with cancer in specific multidisciplinary adolescent units or, failing that, paediatric units, is reflected in the changes in care delivery in Spain in the past decade. Much remains to be done in key components of the management of adolescents with cancer.(c) 2022 Asociaci acute accent on Espan tilde ola de Pediatri acute accent a. Published by Elsevier Espan tilde a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing : Expected and Unexpected Findings

We are deeply grateful to the affected individuals who participated in this study and their families. We thank the Barcelona PID Foundation for patient support and for funding MG-P. We acknowledge Celine Cavallo for English language support. Funding. This study was funded by Instituto de Salud Carlos III, grants PI14/00405 and PI17/00660, cofinanced by the European Regional Development Fund (ERDF).Primary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of genetic defects in PID patients in daily clinical practice. Several NGS approaches are available, from the unbiased whole exome sequencing (WES) to specific gene panels. Here, we report on a 3-year experience with clinical exome sequencing (CES) for genetic diagnosis of PIDs. We used the TruSight One sequencing panel, which includes 4,813 disease-associated genes, in 61 unrelated patients (pediatric and adults). The analysis was done in 2 steps: first, we focused on a virtual PID panel and then, we expanded the analysis to the remaining genes. A molecular diagnosis was achieved in 19 (31%) patients: 12 (20%) with mutations in genes included in the virtual PID panel and 7 (11%) with mutations in other genes. These latter cases provided interesting and somewhat unexpected findings that expand the clinical and genetic spectra of PID-related disorders, and are useful to consider in the differential diagnosis. We also discuss 5 patients (8%) with incomplete genotypes or variants of uncertain significance. Finally, we address the limitations of CES exemplified by 7 patients (11%) with negative results on CES who were later diagnosed by other approaches (more specific PID panels, WES, and comparative genomic hybridization array). In summary, the genetic diagnosis rate using CES was 31% (including a description of 12 novel mutations), which rose to 42% after including diagnoses achieved by later use of other techniques. The description of patients with mutations in genes not included in the PID classification illustrates the heterogeneity and complexity of PID-related disorders

Burkitt-like lymphoma with 11q aberration: a germinal center-derived lymphoma genetically unrelated to Burkitt lymphoma

Burkitt-like lymphoma with 11q aberration is characterized by pathological features and gene expression profile resembling those of Burkitt lymphoma but lacks the MYC rearrangement and carries an 11q-arm aberration with proximal gains and telomeric losses. Whether this lymphoma is a distinct category or a particular variant of other recognized entities is controversial. To improve the understanding of Burkitt-like lymphoma with 11q aberration we performed an analysis of copy number alterations and targeted sequencing of a large panel of B-cell lymphomarelated genes in 11 cases. Most patients had localized nodal disease and a favorable outcome after therapy. Histologically, they were high grade B-cell lymphoma, not otherwise specified (8 cases), diffuse large B-cell lymphoma (2 cases) and only one was considered as atypical Burkitt lymphoma. All cases had a germinal center B-cell signature and phenotype with frequent LMO2 expression. The patients with Burkitt-like lymphoma with 11q aberration had frequent gains of 12q12-q21.1 and losses of 6q12.1-q21, and lacked common Burkitt lymphoma or diffuse large B-cell lymphoma alterations. Potential driver mutations were found in 27 genes, particularly involving BTG2, DDX3X, ETSI , EP300, and GNA13. However, ID3, TCF3, or CCND3 mutations were absent in all cases. These results suggest that Burkitt-like lymphoma with 11q aberration is a germinal center-derived lymphoma closer to high-grade B-cell lymphoma or diffuse large B-cell lymphoma than to Burkitt lymphoma.This work was supported by Asociacion Espanola Contra el Cancer (AECC CICPFI6025SALA), Fondo de Investigaciones Sanitarias Instituto de Salud Carlos III (Miguel Servet program CP13/00159 and PI15/00580, to IS), Spanish Ministerio de Economia y Competitividad, Grant SAF2015-64885-R (EC), Generalitat de Catalunya Suport Grups de Recerca (2017-SGR-1107 I.S. and 2017-SGR-1142 to EC), and the European Regional Development Fund "Una manera de fer Europa". JERZ was supported by a fellowship from the Generalitat de Catalunya AGAUR FI-DGR 2017 (2017 FI_B01004). EC is an Academia Researcher of the "Institucio Catalana de Recerca i Estudis Avancats" (ICREA) of the Generalitat de Catalunya. This work was developed at the Centro Esther Koplowitz, Barcelona, Spain. The group is supported by Accio Instrumental d'Incorporacio de Cientifics i Tecnolegs PERIS 2016 (SLT002/16/00336) from the Generalitat de Catalunya

Burkitt-like lymphoma with 11q aberration: A germinal center derived lymphoma genetically unrelated to Burkitt lymphoma

Burkitt-like lymphoma with 11q aberration is characterized by pathological features and gene expression profile resembling Burkitt lymphoma but lack MYC rearrangement and carries an 11q-arm aberration with proximal gains and telomeric losses. Whether these lymphomas are a distinct category or a particular variant of other recognized entities is controversial. To improve the understanding of Burkitt-like lymphoma with 11q aberration we have performed an analysis of copy number alterations and targeted sequencing of a large panel of B-cell lymphoma related genes in 11 cases. Most patients had localized nodal disease and a favourable outcome after therapy. Histologically, they were high grade B-cell lymphoma, not otherwise specified (8 cases), diffuse large B-cell lymphoma (2 cases) and only one was considered as atypical Burkitt lymphoma. All cases had a germinal center B-cell signature and phenotype with frequent LMO2 expression. Burkitt-like lymphoma with 11q aberration had frequent gains of 12q12-q21.1 and losses of 6q12.1-q21, and lacked common Burkitt lymphoma or diffuse large B-cell lymphoma alterations. Potential driver mutations were found in 27 genes, particularly involving BTG2, DDX3X, ETS1, EP300, and GNA13. However, ID3, TCF3, or CCND3 mutations were absent in all cases. These results suggest that Burkitt-like lymphoma with 11q aberration is a germinal center derived lymphoma closer to high grade B-cell lymphoma or diffuse large B-cell lymphoma rather than Burkitt lymphoma.Copyright © 2019, Ferrata Storti Foundation