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Resumen Introduccion Los resultados de los pacientes con diagnostico de leucemia linfoblastica aguda con cromosoma de Philadelphia (LLA-Ph) continuan siendo desfavorables comparados con los otros tipos de leucemias linfoblasticas agudas, pese a las mejoras en los tratamientos farmacologicos y los avances del trasplante de progenitores hematopoyeticos (TPH). Pacientes y metodos Se ha analizado el papel del TPH alogenico en pacientes diagnosticados de LLA-Ph mediante un estudio multicentrico donde se recogen datos pertenecientes a 70 pacientes reportados por el Grupo Espanol de Trasplante Hematopoyetico (GETH), diagnosticados de esta enfermedad trasplantados en distintos hospitales espanoles entre los anos 1998 y 2014. Resultados La realizacion del TPH a partir del ano 2004, en primera remision completa (RC) y con el empleo de timoglobulina (ATG) como parte del acondicionamiento, impacto favorablemente en la supervivencia global (SG). El TPH a partir del ano 2004 en primera RC, asi como el tratamiento con ATG y el desarrollo de enfermedad de injerto contra receptor aguda (EICRa), aumentaron la supervivencia libre de eventos (SLE). La administracion de imatinib, asi como la ausencia de enfermedad minima residual previas al TPH, junto con la EICRa redujeron la probabilidad de recaida. La edad del paciente inferior a 10 anos, el estado de primera RC y el empleo de ATG en el acondicionamiento disminuyeron la mortalidad relacionada con el TPH. Conclusiones Los pacientes en primera RC que han recibido ATG durante el acondicionamiento presentan mayores SG y SLE. La indicacion de TPH deberia considerarse en estas situaciones.

Background Acute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBL–activated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475). Patients and Methods Before the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 × 106/IU/m2) of subcutaneous interleukin-2. The primary study endpoint was AML relapse-free survival. We needed to include 35 patients to demonstrate a 50% reduction in relapses. Results Seven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 × 106 cells/kg (range, 6.92 × 106 to 193.2 × 106 cells/kg). We observed chimerism in 4 patients (median chimerism, 0.065%; range, 0.05-0.27%). After a median follow-up of 33 months, the disease of 6 patients (85.7%) remained in complete remission. The 3-year overall survival was 83.3% (95% confidence interval, 68.1-98.5), and the cumulative 3-year relapse rate was 28.6% (95% confidence interval, 11.5-45.7). The study was terminated early because of low patient recruitment. Conclusion This study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers.

IntroductionAcute 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 analysisPatients 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 disseminationThis 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 numberEudraCT code: 2015-001901-15, ClinicalTrials.gov Identifier:NCT02763475.