Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges

Abstract

Acute myeloid leukemia (AML) is a disease with heterogeneous prognosis based on the clinical, cytogenetic, and molecular profile of the patient. Despite high post-induction remission rates in adult patients up to 40% of patients relapse. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and potentially curative post-remission treatment for AML. 1 The antileukemic effect of allo-HSCT depends on the cytotoxicity of the pretransplant conditioning therapy and the posttransplant graft versus leukemia (GVL) effect. In a meta-analysis, allo-HSCT significantly improves survival in patients in first complete remission (CR) with poor-risk and intermediate-risk cytogenetic abnormalities (poor-risk: HR -0.73; 95% CI, 0.59-0.90); (intermediate-risk AML: HR, 0.83%-95% CI, 0.74-0.93). 2,3 The introduction of non-myeloablative (NMA) and reduced intensity conditioning (RIC) regimens, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have allowed for a larger application of allo-HSCT to older patients and those with comorbidities. Although Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). Reduced intensity regimens, alternative graft sources, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have led to a wider application of allo-HSCT to eligible patients. Unfortunately, 30-40% of patients with AML will relapse after transplant and this is the major cause of treatment failure. Careful consideration should be paid in choosing the type of graft, graft source, and conditioning regimen to minimize the risk of disease recurrence. In addition, maintenance therapy following allo-HSCT is a potential method to keep the disease in remission, especially in those with high-risk disease characteristics. Pharmacological targeted agents with low side effect profile such as tyrosine kinase inhibitors, hypomethylating agents (HMAs), HDAC inhibitors, antibody drug conjugates (ADCs), isocitrate dehydrogenase inhibitors, and hedgehog inhibitors may prevent relapse in posttransplant setting and are under investigation. Immunological therapies including donor lymphocyte infusions (DLIs), natural killer (NK) cell therapy, peptide vaccine targeting tumor antigens, and adoptive T-cell therapies all hold promises in this area as well. As targeted agents and immunotherapies continue to be developed, patients at high risk of recurrence may benefit from prophylactic maintenance therapy. Here we review the current landscape in this rapidly evolving clinical setting. K E Y W O R D S Acute myeloid leukemia, Allogeneic Transplant, Immunotherapy, Posttransplant relapse, Targeted agents

Allogeneic hematopoietic stem cell transplant in pediatric acute myeloid leukemia: Lessons learnt from a tertiary care center in India

“…26,27 Post-transplant targeted therapy with novel agents is under active investigation, and multiple agents including epigenetic modifiers, tyrosine kinase inhibitors, immunomodulators, and antibody-drug conjugates are currently in various stages of development. 28 The incidence of both acute and chronic GVHD (7% and 9%, respectively) in our cohort of patients was lower than contemporary trials (12%-14%). 29,30 This may be due to the longer duration of administration of cyclosporine in our patients (9-12 months) as against the more accepted duration of 6 months; this has been shown to reduce GVHD.…”

“…Commonly employed strategies include chemotherapy, donor leukocyte infusion, and second allo‐HSCT, but these options still yield unacceptably low rates of long‐term remission 26,27 . Post‐transplant targeted therapy with novel agents is under active investigation, and multiple agents including epigenetic modifiers, tyrosine kinase inhibitors, immunomodulators, and antibody‐drug conjugates are currently in various stages of development 28 …”

European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

“…Potential innovative strategies to improve outcomes of this AML subgroup should focus on pretransplant treatment to increase the response rate and prevent early relapse, as well as maintenance after alloSCT to enhance the graft-versus-leukemia effect and avoid posttransplant relapse. 32 Novel current available agents, approved for AML, could contribute to improve outcome of high-risk patients obtained with intensive chemotherapy. Specifically, 1:5 daunorubicin/cytarabine liposomal formulation CPX-351 has demonstrated its role in elderly patients diagnosed with AML with myelodysplasia-related changes, with a clear impact on those patients bridged to alloSCT after treatment with this agent.…”