Conditioning regimen intensity and low-dose azacitidine maintenance after allogeneic hematopoietic cell transplantation for acute myeloid leukemia

Ali, Naveed; Tomlinson, Benjamin; Metheny, Leland; Goldstein, Steven C.; Fu, Pingfu; Cao, Shufen; Caimi, Paolo; Patel, Rushang D.; Varela, Juan Carlos; Andrade, Luisa; Balls, Jason; Baer, Linda; Smith, Megan; Smith, Tori; Nelson, Megan; Lima, Marcos de; Mori, Shahram

doi:10.1080/10428194.2020.1789630

Cited by 21 publications

(19 citation statements)

References 36 publications

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“…The remaining 34 articles underwent full-length review and 20 of those were excluded for the aforementioned reasons. Ultimately, the eligibility criteria for our meta-analysis were met by 14 studies: two RCTs, two prospective cohort study, and 10 retrospective cohort studies ( 14 – 22 , 25 , 27 – 29 ). Twelve of these compared azacitidine maintenance to observation, whereas two compared decitabine maintenance to observation.…”

Section: Resultsmentioning

confidence: 99%

Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

et al. 2022

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IntroductionHypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients.Materials and MethodsThe Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by two investigators to identify relevant studies published inception to 18 November 2021. These trials compared HMA maintenance to observation following allo-SCT for AML or myelodysplastic syndrome.ResultsThe meta-analysis eligibility criteria were fulfilled by 14 studies. The overall survival and relapse-free survival of the HMA maintenance group were superior to the observation group, with a pooled risk ratio (RR) of 1.38 and 1.46, respectively. Moreover, the cumulative incidence of relapse was significantly lower in those who received HMAs. The HMA group also had lower non-relapse mortality compared with the observation group. Overall, the incidences of grades III–IV acute graft-vs.-host disease (GVHD) and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone.ConclusionsThe current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD.

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Section: Resultsmentioning

confidence: 99%

Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

et al. 2022

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“…In this study declining donor chimerism served as a proxy for molecular relapse, and the findings suggest that azacitidine may be more effective when used to treat a low disease burden. This has inspired numerous studies of prophylactic post-transplant azacitidine ( 45 – 50 ), although a randomized trial versus best supportive care recently failed to demonstrate a survival benefit ( 51 ). In contrast, a randomized trial of prophylactic low-dose decitabine in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) given post-transplant led to a reduction in AML relapses compared to no intervention ( 52 ).…”

Section: Lower Intensity Therapymentioning

confidence: 99%

Treatment of AML Relapse After Allo-HCT

2021

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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.

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“…Both decitabine and azacitidine are HMAs and have been safely and effectively used for maintenance treatment of AML and myelodysplastic syndrome (MDS) after transplantation (14)(15)(16)(17)(18)(19)(20). The main effect of post-transplantation hypomethylation treatment is to prevent primary disease relapse and reduce graftversus-host disease (GVHD).…”

Section: Introductionmentioning

confidence: 99%

Maintenance Treatment With Low-Dose Decitabine After Allogeneic Hematopoietic Cell Transplantation in Patients With Adult Acute Lymphoblastic Leukemia

et al. 2021

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BackgroundPost-transplant relapse remains a principal leading cause of failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with adult acute lymphoblastic leukemia (ALL). The aim of this study was to investigate the efficacy and safety of low-dose decitabine on the prevention of adult ALL relapse after allo-HSCT.MethodsIn this prospective study, we enrolled 34 patients with ALL who underwent allo-HSCT from August 2016 to April 2020 and received low-dose decitabine maintenance treatment after transplantation. The primary objectives were cumulative incidence of relapse rate (CIR), overall survival (OS), and disease-free survival (DFS). The secondary objectives were graft-versus-host disease (GVHD) and safety.ResultsAmong the enrolled 34 patients, 6 patients relapsed and 6 patients died. The 2-year CIR, OS, and DFS were 20.2, 77.5, and 73.6%, respectively. Subgroup analysis revealed the 2-year CIR, OS, and DFS rates of 12 patients with T-ALL/lymphoblastic lymphoma (LBL) were 8.3, 90, and 81.5%, respectively. None of the seven patients with T-ALL relapsed. During maintenance treatment, only one patient (2.9%) developed grade IV acute GVHD and four (11.8%) patients had severe chronic GVHD. Thirty-two patients (94.1%) developed only grade I to II myelosuppression, and two patients (5.8%) developed grade III to IV granulocytopenia.ConclusionsMaintenance treatment with low-dose decitabine after allo-HSCT may be used as a therapeutic option to reduce relapse in patients with adult ALL, especially in patients with T-ALL. Our findings require confirmation in larger-scale controlled trials.Clinical Trial RegistrationChinese Clinical Trials Registry, identifier ChiCTR1800014888.

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Conditioning regimen intensity and low-dose azacitidine maintenance after allogeneic hematopoietic cell transplantation for acute myeloid leukemia

Cited by 21 publications

References 36 publications

Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

Treatment of AML Relapse After Allo-HCT

Maintenance Treatment With Low-Dose Decitabine After Allogeneic Hematopoietic Cell Transplantation in Patients With Adult Acute Lymphoblastic Leukemia

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