Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukaemia: results of the NCRI acute myeloid leukemia 16 trial

Reduced Intensity Conditioning (RIC) transplantation is increasingly offered to older patients with acute myeloblastic leukemia (AML). We have previously shown that a RIC allograft, particularly from a sibling donor is beneficial in intermediate risk patients aged 35-65 years. We here present analyses from the NCRI AML16 trial extending this experience to older patients aged 60-70 inclusive lacking favorable risk cytogenetics 932 patients were studied, with RIC transplant in first remission given to 144 (sibling n=52, MUD n=92) with median follow-up for survival from CR of 60 months. Comparisons of transplant versus not are carried out using Mantel-Byar analysis. Among the 144 allografts, 93 had intermediate risk cytogenetics, 18 adverse and 33 were unknown. In transplanted patients survival was 37% at 5 years, and while the survival for siblings (44%) was better than that for MUDs (34%) this was not significant (p=0.2). When comparing RIC versus chemotherapy survival was significantly improved (37% vs 20%, HR 0.67 (0.53-0.84) p

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

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.

Leukaemia

Acute myeloblastic leukaemia (AML) - Acute lymphoblastic leukaemia (ALL) - Chronic myeloid leukaemia (CML) - Chronic lymphocytic leukaemia (B-CLL) - Prolymphocytic leukaemia (PLL) - Hairy cell leukaemia and variant - Large granular lymphocyte leukaemia (LGLL) - Adult T-cell leukaemia-lymphoma (ATLL)