Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk acute myeloid leukemia (AML) represents the only curative option. Progress has been made in the last two decades in the pre-transplant induction therapies, supportive care, selection of donors and conditioning regimens that allowed to extend the HSCT to a larger number of patients, including those aged over 65 years and/or lacking an HLA-identical donor. Furthermore, improvements in the prophylaxis of the graft-versus-host disease and of infection have dramatically reduced transplant-related mortality. The relapse of AML remains the major reason for transplant failure affecting almost 40–50% of the patients. From 10 to 15 years ago to date, treatment options for AML relapsing after HSCT were limited to conventional cytotoxic chemotherapy and donor leukocyte infusions (DLI). Nowadays, novel agents and targeted therapies have enriched the therapeutic landscape. Moreover, very recently, the therapeutic landscape has been enriched by manipulated cellular products (CAR-T, CAR-CIK, CAR-NK). In light of these new perspectives, careful monitoring of minimal-residual disease (MRD) and prompt application of pre-emptive strategies in the post-transplant setting have become imperative. Herein, we review the current state of the art on monitoring, prevention and treatment of relapse of AML after HSCT with particular attention on novel agents and future directions.

Serum proteomics screening intercellular adhesion molecule-2 improves intermediate-risk stratification in acute myeloid leukemia

“…Currently, chemotherapy and hematopoietic stem cell transplantation are the main treatments for AML. 20 To verify the effect of ICAM2 between treatment groups in intermediate-risk AML, we compared the survival curves of patients who received and did not receive bone marrow transplantation. Compared with the standard chemotherapy group, the OS of intermediate-risk AML patients receiving bone marrow transplantation was significantly prolonged (HR = 0.316, 95% CI = 0.207–0.482, p < 0.0001) [ Figure 5(a) ].…”

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

“…However, there is a current need to conduct prospective studies to assess the benefits and risk of a second allo-HSCT, as most data have been derived from retrospective investigations. Impressive overviews of a second allo-HSCT in the setting of relapsed AML post-allo-HSCT has been published elsewhere[ 171 , 179 ].…”

“…, ipililumab and magrolimab), monoclonal antibodies (gemtuzumab ozogamicin and the anti-IL3 agent CLS360) and vaccines are displaying promising results. In addition, several novel targeted agents are currently being developed and/or investigated[ 171 , 179 ]: Small-molecule inhibitors (apart from FLT3 inhibitors and the BCL-2 inhibitor venetoclax), trametinib (anti-MEK agent), glasdegib (a molecule that interacts with the Hedgehog pathway), and uproleselan (anti-E-selectin agent); histone-deacetylase inhibitors, panobinostat; and IDH1/2 inhibitors, ivosidenib and enasidenib.…”

MRD as Biomarker for Response to Donor Lymphocyte Infusion after Allogeneic Hematopoietic Cell Transplantation in Patients with AML

“…Relapse of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (alloHCT) remains a major challenge [1][2][3]. Donor lymphocyte infusions (DLIs) after alloHCT can target leukemic cells through the enhancement of the graft-versus-leukemia (GvL) effect, which can reduce the relapse risk or even treat clinical relapse [1,2,[4][5][6].…”