Treatment of AML Relapse After Allo-HCT

Abstract

With advances in allogeneic hematopoietic stem cell transplant (allo-HCT), disease relapse has replaced transplant-related mortality as the primary cause of treatment failure for patients with acute myeloid leukemia (AML). The efficacy of allo-HCT in AML is a consequence of a graft-versus-leukemia (GVL) effect that is mediated by T lymphocytes, and unique mechanisms of immune evasion underlying post-allo-HCT AML relapses have recently been characterized. Relapsed AML following allo-HCT presents a particularly vexing clinical challenge because transplant-related toxicities, such as graft-versus-host (GVHD) and infections, increase the risk of treatment-related morbidity and mortality. In general, the prognosis of relapsed AML following allo-HCT is poor with most patients failing to achieve a subsequent remission and 2-year survival consistently <15%. The two factors that have been found to predict a better prognosis are a longer duration of post-transplant remission prior to relapse and a lower disease burden at the time of relapse. When considered in combination with a patient’s age; co-morbidities; and performance status, these factors can help to inform the appropriate therapy for the treatment of post-transplant relapse. This review discusses the options for the treatment of post-transplant AML relapse with a focus on the options to achieve a subsequent remission and consolidation with cellular immunotherapy, such as a second transplant or donor lymphocyte infusion (DLI). While intensive reinduction therapy and less intensive approaches with hypomethylating agents have long represented the two primary options for the initial treatment of post-transplant relapse, molecularly targeted therapies and immunotherapy are emerging as potential alternative options to achieve remission. Herein, we highlight response and survival outcomes achieved specifically in the post-transplant setting using each of these approaches and discuss how some therapies may overcome the immunologic mechanisms that have been implicated in post-transplant relapse. As long-term survival in post-transplant relapse necessarily involves consolidation with cellular immunotherapy, we present data on the efficacy and toxicity of both DLI and second allo-HCT including when such therapies are integrated with reinduction. Finally, we provide our general approach to the treatment of post-transplant relapse, integrating both novel therapies and our improved understanding of the mechanisms underlying post-transplant relapse.

Efficacy and feasibility of Pharmacoscopy-guided treatment for acute myeloid leukemia patients that exhausted all registered therapeutic options

“…Despite the expansion of targeted therapies for AML patients, as well as other approaches such as post-transplant maintenance therapy, relapse of AML remains the main cause of mortality in patients with this entity. The exceptionally poor prognosis in this patient group is aggravated further by the very limited availability of registered therapy options at this stage and the rapidly progressive nature of their disease 3 . Thus, improving the prognosis of patients at relapse of AML that have exhausted all registered therapy options remains a critical unsolved issue.…”

“…We found that the screening procedure is fast, taking a median of only 5 days to deliver the necessary results and new therapy protocols could be administered within a median of 11 days after receiving the pharmacoscopy results. Thus the procedure does not significantly slow down clinical decision-making, which is a key concern in a rapidly progressing disease such as AML at relapse 1,3 .…”

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT

“…Currently available treatments, including intensive chemotherapy, DLI, etc., were partially hindered by poor efficacy and toxicity ( 2 , 4 , 19 ). Previous researches on IC treatment for post-transplantation AML relapse have demonstrated CR rates from 13% to 71% and 1-year OS from 25% to 34.4% ( 20 ). A recent study including 175 patients showed a remission rate of 36% and median OS of 188 days, while early mortality within 28 days occurred in 12% patients ( 21 ).…”

Construction of circRNA–miRNA–mRNA Network Reveal Functional circRNAs and Key Genes in Acute Myeloid Leukemia

“…However, they are still at risk for drug resistance and disease recurrence, thus resulting in shorter survival and poorer International Journal of General Medicine 2023:16 1491-1504 quality of life. 3 Studying the molecular mechanism of AML development takes on a great significance in finding novel therapeutic targets and facilitating AML prognosis.…”