Periosteal Ewing Sarcoma with Distant Metastases: Report of Two Patients and Review of the Literature.

Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in the long tubular bone diaphysis. PES rarely develops distant metastases. We report two patients of this rare ES location that were found on the distal tibial shaft and proximal femoral diaphysis of a 21-year-old man and an 8-year-old boy, respectively. Both patients were treated with neoadjuvant chemotherapy, wide resection, and adjuvant chemotherapy. One of our patients had lung metastases at the time of diagnosis and died 5 years later. The other patient presented intramedullary humeral bone metastasis 19 years after diagnosis. There has been no evidence of disease in the 26 years of follow-up. Close follow-up of periosteal ES is recommended because distant metastases may exceptionally occur, even several years after diagnosis.

Case Report: The Value of Genomic Analysis in a Case of Megakaryoblastic Leukemia With Atypical Initial Manifestation.

We report the case of a 7-month-old female patient who developed acute megakaryoblastic leukemia 6 months after the appearance of skull bone lesions. Initial evaluation and diagnosis of this patient were challenging and only achieved thanks to genomic analysis by NGS (next generation sequencing). It is unusual for the initial manifestation of acute megakaryoblastic leukemia to be a skull bone lesion. Extramedullary acute myeloid leukemia (eAML), also known as myeloid sarcoma (MS), often occurs simultaneously with acute myeloid leukemia (AML), although it may precede AML. Genomic analysis based on a NGS panel (Oncomine Childhood Cancer Research Assay) detected a RBM15::MKL1 fusion, a consequence of a t (1;22)(p13;q13) translocation, establishing the diagnosis of acute megakaryoblastic leukemia and enabling disease follow-up by qPCR. A diagnosis of eAML is built up from various findings in radiological, histological, immunophenotypic and genomic studies; when the tumor appears de novo, diagnosis is more complicated. We emphasize the importance of a multidisciplinary team in the initial approach to rare tumors and the use of genomic studies to contribute to the knowledge of these neoplasms, risk stratification and treatment planning.

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine.

Relapsed and refractory (R/r) disease in paediatric acute leukaemia remains the first reason for treatment failure. Advances in molecular characterisation can ameliorate the identification of genetic biomarkers treatment strategies for this disease, especially in high-risk patients. The purpose of this study was to analyse a cohort of R/r children diagnosed with acute lymphoblastic (ALL) or myeloid (AML) leukaemia in order to offer them a targeted treatment if available. Advanced molecular characterisation of 26 patients diagnosed with R/r disease was performed using NGS, MLPA, and RT-qPCR. The clinical relevance of the identified alterations was discussed in a multidisciplinary molecular tumour board (MTB). A total of 18 (69.2%) patients were diagnosed with B-ALL, 4 (15.4%) with T-ALL, 3 (11.5%) with AML and 1 patient (3.8%) with a mixed-phenotype acute leukaemia (MPL). Most of the patients had relapsed disease (88%) at the time of sample collection. A total of 17 patients (65.4%) were found to be carriers of a druggable molecular alteration, 8 of whom (47%) received targeted therapy, 7 (87.5%) of them in addition to hematopoietic stem cell transplantation (HSCT). Treatment response and disease control were achieved in 4 patients (50%). In conclusion, advanced molecular characterisation and MTB can improve treatment and outcome in paediatric R/r acute leukaemias.

Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic activated and expanded natural killer cells as consolidation therapy for paediatric acute myeloblastic leukaemia.

INTRODUCTION: Acute myeloblastic leukaemia (AML) constitutes the second most common haematological malignancy in the paediatric population. Current treatment regimens are based on the administration of polychemotherapy, combining high doses of cytarabine with anthracyclines and topoisomerase inhibitors. Allogeneic haematopoietic stem cell transplantation (HSCT) is an option for high-risk patients with AML (and for intermediate-risk patients if a sibling donor is available). With this strategy, AML survival has increased substantially; however, it has remained stagnant at approximately 60%, with relapse being the principal culprit. The predominant role of the immune system and natural killer (NK) cells in controlling paediatric AML has gained importance within the context of HSCT. In this protocol, we propose incorporating this cell therapy as an adjuvant treatment through the infusion of activated and expanded haploidentical NK (NKAE) cells in paediatric patients with AML who are in cytological remission after completing consolidation therapy, and with no indication for HSCT. METHODS AND ANALYSIS: Patients up to 30 years of age, diagnosed with AML, in their first cytological remission, who have completed both the induction and the consolidation phases of chemotherapy and do not meet the criteria for allogeneic HSCT are eligible. The patients will receive two doses of NKAE cells once a week, using a GMP K562-mbIL15-41BBL stimulus from a haploidentical donor and interleukin 2 subcutaneously. The patients will then be followed up for 36 months to assess the primary endpoint, which is the probability of relapse after NK cell infusion. ETHICS AND DISSEMINATION: This clinical trial was approved by the Clinical Research Ethics Committee of La Paz University Hospital and The Spanish Agency of Medicines and Medical Devices. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. TRIAL REGISTRATION NUMBER: EudraCT code: 2015-001901-15, ClinicalTrials.gov Identifier: NCT02763475.