Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials

The use of allogeneic hematopoietic stem cell transplantation (HSCT) is recommended during the first complete remission of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). However, only 30% of these cases have fully matched sibling donors (MSDs). Alternatively, matched unrelated donors (MUDs) and haploidentical (haplo) donors from first-degree relatives increase the access to transplantation, with some reported differences in outcomes. The current systematic review and meta-analysis was conducted with the aim of summarizing the results of those studies to compare the efficacy and toxicity of MSD-HSCT and MUD-HSCT versus haplo-HSCT for patients with AML or MDS. Articles published before September 15, 2018, were individually searched for in two databases (MEDLINE and EMBASE) by two investigators. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel–Haenszel method. A total of 14 studies met the eligibility criteria and were included in the meta-analysis. The overall survival rates were not significantly different between the groups, with pooled odds ratios of the chance of surviving at the end of the study when comparing haplo-HSCT to MSD-HSCT and comparing haplo-HSCT to MUD-HSCT of 0.85 (95% CI: 0.70 to 1.04; I 2 = 0%) and 1.12 (95% CI: 0.89 to 1.41; I 2 = 33%), respectively. The pooled analyses of other outcomes also showed comparable results, except for the higher grade 2 to 4 acute graft-versus-host disease (GvHD) for patients who received haplo-HSCT than those who received MSD-HSCT, and the better GvHD-free, relapse-free survival and the lower chronic GvHD than the patients in the MUD-HSCT group. These observations suggest that haplo-HSCT is a reasonable alternative with comparable efficacy if MSD-HSCT and MUD-HSCT cannot be performed. Nonetheless, the primary studies included in this meta-analysis were observational in nature, and randomized-controlled trials are still needed to confirm the efficacy of haplo-HSCT.

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Acute Myeloid Leukemia (AML) Following Myelodysplastic Syndrome (MDS) and Failure of Therapy with Hypomethylating Agents (HMA): An Emerging Entity With a Poor Prognosis

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2013.07.087 ◽

2013 ◽

Vol 13 ◽

pp. S379

Author(s):

Hady Ghanem ◽

Elias Jabbour ◽

Xuelin Huang ◽

Farhad Ravandi ◽

Guillermo Garcia-Manero ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Hypomethylating Agents ◽

Acute Myeloid

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Hypomethylating Agents As Maintenance Treatment Following Allogeneic Hematopoietic Transplant in Children's Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome: A Single Center Study

Blood ◽

10.1182/blood-2021-151869 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4892-4892

Author(s):

Yongsheng Ruan ◽

Danfeng Xie ◽

Xuan Liu ◽

Qiujun Liu ◽

Chunfu Li ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Maintenance Treatment ◽

Cell Transplant ◽

Hypomethylating Agents ◽

Single Center ◽

Single Center Study ◽

Acute Myeloid ◽

Center Study

Abstract Regarding children's patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), disease relapse remains the most common reason for transplant failure and patient death. We implemented a single center study to investigate hypomethylating agents (HMA) as maintenance treatment after HSCT for children AML or MDS. We retrospectively analyzed 30 patients with AML or MDS including 63 courses of azacytidine (AZA) and 69 courses of decitabine (DEC) from January 1, 2018 to June 30, 2021 (Figure 1A). Either AZA (37.5mg/m 2 to 75 mg/m 2 for consecutive 5-7 days) or DEC (5 mg/m 2 for consecutive 5 days) was administrated 90 days post-transplantation as first course. Furthermore, the interval of HMA treatment was 1.5-month hereafter for in total of a year (Figure 1B). Patients that received at least one course of HMA treatment were included in this study. The patient characteristics was shown in Table 1. We found that the disease-free survival (DFS) and overall survival (OS) were 82.96±6.95% and 85.51±6.72%, respectively (Figure 1C, D). Based on Common Terminology Criteria for Adverse Events (CTCAE) criteria, only Grade 1 to 2 leukopenia (P<0.001), anemia (P=0.043), and thrombocytopenia (P=0.033) were found between complete blood count (CBC) of pre-treatment and post-treatment. Subgroup analysis indicated that the difference was mainly come from DEC group [leukopenia (P<0.001), anemia (P=0.001), and thrombocytopenia (P=0.190)] instead of AZA group [leukopenia (P=0.476), anemia (P=0.443), and thrombocytopenia (P=0.095)]. No nausea/vomiting, or elevated ALT, or elevated creatinine, or rash, or de novo/exacerbated GVHD were observed. Moreover, there were no difference of activation T cells populations (CD25 and HLA-DR) among 7 courses except CD3+HLADR+/CD3+ and CD8+HLADR+/CD8+ in course 1 vs course 4 (P= 0.0354 and P=0.0163, respectively, Figure 1E). Furthermore, a trend of increased percentage of CD3+HLADR+/CD3+, or CD4+HLADR+/CD4+, or CD8+HLADR+/CD8+ and decreased percentage of CD3+CD25+/CD3+, or CD4+CD25+/CD4+, or CD8+CD25+/CD8+ was found in relapsed group, despite there was no significant difference. Interestingly, DEC significantly reduced population of CD3+HLADR+/CD3+, or CD4+HLADR+/CD4+, or CD8+HLADR+/CD8+ compared to AZA (P<0.001, P<0.001, or P<0.001, respectively). In conclusion, both AZA and DEC as HMA maintenance treatment following HSCT in children AML or MDS was safe, and the outcome was encouraging. A further large cohort of randomization of AZA and DEC study is required. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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