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

INTRODUCTION: Hypomethylating 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 METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The 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.

Efficacy of Targeted Immunotherapy as Induction or Salvage Therapy in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Monoclonal antibodies targeting cluster of differentiation (CD) proteins have been incorporated into standard treatments for multiple types of hematologic malignancies, including acute lymphoblastic leukemia (ALL). This systematic review and meta-analysis investigated the efficacy of using CD-targeted antibodies for ALL. MATERIALS AND METHODS: The EMBASE and MEDLINE databases were searched for research papers using immunotherapy- and ALL-related terms from inception to July 2021. Eligible studies were randomized, controlled trials (RCTs) or cohort studies in which ALL patients received CD-targeted immunotherapy or conventional chemotherapy as the induction or salvage therapy. The reports had to report our primary outcomes of interest: overall survival (OS), relapse-free survival (RFS), or complete remission (CR), with the patient number for each outcome. The effect estimates with 95% confidence interval (CI) from each study were combined to calculate the pooled-effect estimate, using the Hantel-Maenszel method. RESULTS: Five RCTs and 9 retrospective cohort studies were eligible for the meta-analysis. ALL patients given CD-targeted immunotherapy in the induction or salvage therapy had significantly higher OS and RFS rates than those administered conventional chemotherapy only, with pooled odds ratios (OR) of 2.11 (95% CI, 1.76-2.53; I2, 0%) and 2.25 (95% CI, 1.62-3.14; I2, 61%), respectively. The rates of achieving CR and minimal residual disease negativity were also higher for the immunotherapy group, with pooled ORs of 1.70 (95% CI, 1.07-2.69; I2, 79%) and 2.98 (95% CI, 1.17-7.58; I2, 90%), while developing less risk for febrile neutropenia (pooled OR, 0.22; 95% CI, 0.08-0.58; I2, 84%). Subgroup analyses revealed that all antibody types yielded dramatically better OS rates than those for patients administered chemotherapy alone. CONCLUSIONS: The ALL patients receiving CD-targeted immunotherapy as induction or salvage therapy had significantly higher response rates and survival outcomes, as well as lower odds of acquiring febrile neutropenia, than the patients given conventional chemotherapy.

Clinical Outcomes Based on Measurable Residual Disease Status in Patients with Core-Binding Factor Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.

Measurable residual disease (MRD) response during acute myeloid leukemia (AML) treatment is a gold standard for determining treatment strategy, especially in core-binding factor (CBL) AML. The aim of this study was to critically review the literature on MRD status in the CBF-AML to determine the overall impact of MRD status on clinical outcomes. Published studies in the MEDLINE and EMBASE databases from their inception up to 1 June 2019 were searched. The primary end-point was either overall survival (OS) or recurrence-free survival (RFS) between MRD negative and MRD positive CBF-AML patients. The secondary variable was cumulative incidence of relapse (CIR) between groups. Of the 736 articles, 13 relevant studies were included in this meta-analysis. The MRD negative group displayed more favorable recurrence-free survival (RFS) than those with MRD positivity, with a pooled odds ratio (OR) of 4.5. Moreover, OS was also superior in the MRD negative group, with a pooled OR of 7.88. Corroborating this, the CIR was statistically significantly lower in the MRD negative group, with a pooled OR of 0.06. The most common cutoff MRD level was 1 × 10-3. These results suggest that MRD assessment should be a routine investigation in clinical practice in this AML subset.