Biology and management of relapsed acute myeloid leukaemia

Abstract

SummaryDisease relapse remains the major cause of treatment failure in adults with acute myeloid leukaemia (AML). This reflects both the failure of current salvage regimens and the absence of effective strategies to secure long-term disease-free survival in those patients who achieve a second remission. Recent progress in understanding the pathogenesis of relapsed disease has enabled the identification of a variety of dysregulated molecular pathways and these now provide a rational basis for the design of novel targeted therapies. At the same time, advances in allogeneic stem-cell transplantation have permitted the extension of the curative potential of allografting to patients in whom it was previously contraindicated. As a result, a range of novel drug and transplant therapies has become available in patients with relapsed AML, and it is realistic to anticipate that a co-ordinated assessment of their clinical and biological impact will provide the basis for the design of future, more effective treatments in relapsed disease.

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

“…There is an ongoing need for new and better treatments for patients with advanced disease and poor risk cytogenetics who have an unsatisfactory outcome with any treatment regimen. These risks are often compounded by the cumulative morbidity of multiple reinduction therapies [29] and pre-HSCT infections. Nonetheless we observed continuing freedom from relapse in 66% of such patients, supporting the promise of leukemia control using RI allografts.…”

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center

“…24 Patients in the high-risk group and with time of remission less than 6 months should be referred to clinical trials or better supportive care. [25][26][27] In our cohort, 59 out of 61 patients presented active disease, i.e., patients who had failure in previous treatments, including previous ASCT. Despite that, our population was relatively heterogeneous; the present manuscript reports the experience of a large reference Comprehensive Cancer Center in southern Europe that serves a 3 million habitant area in the North of Portugal.…”

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study

“…6 However, we have recently shown that a chemo-immunotherapy combining Gemtuzumab Ozogamicin (GO), intermediate dose Ara-C and Mitoxantrone (MIDAM regimen) 7 represents a valid therapeutic option in this setting, allowing to achieve an overall response (OR) rate of 63%, and a disease-free and OS rates of 41 and 53%, respectively, at 2 years. Moreover, we have also shown that normal karyotype (NK) AML patients, receiving the MIDAM protocol and who had a favourable molecular profile (that is, mutated nucleophosmin gene (NPM1 þ ) without internal tandem duplications of the fms-like tyrosine kinase 3 gene (FLT3-ITDÀ)), retained a good prognosis compared with other subgroups with NK.…”