Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

Abstract

PurposeThe aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes—refractory anemia with excess of blasts (MDS-RAEB).MethodsThe current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens.ResultsA total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2–21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at < 60 years of age, the CR rate in the decitabine priming group was significantly higher than in the chemotherapy group (65.5 vs. 31.0%, p = 0.009). Survival benefit of decitabine priming was apparent in patients at < 60 years of age (22.4 months with 95% CI of 6.7–38.1 vs. 14.7 months with 95% CI of 11.4–18.0 months in the chemotherapy group, p = 0.028), patients with intermediate and unfavorable karyotypes (22.4 months with 95% CI of 15.1–29.7 vs. 11.9 months with 95% CI of 4.0–19.8 months in the chemotherapy group, p = 0.042), and patients with mutated splicing factor genes (35.3 months with 95% CI of 21.4–49.2 vs. 17.8 months with 95% CI of 13.8–21.8 months in the chemotherapy group, p = 0.039). Grade 3–4 hematological and non-hematological toxicities were not significantly different between the two groups.ConclusionsDecitabine priming prior to low-dose chemotherapy could improve treatment responses in patients with MDS-RAEB.

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients

“…DLI has been used as a type of allo-TLI for decades; however, non-ablative chemotherapy followed by HLA-mismatched stem cell transplantation, also referred to as “micro-transplantation”, has also been used to treat myeloid malignancies, with a better response, faster blood cell recovery, and lower TRM rate than conventional regimens, especially in elderly AML patients and patients with MDS ( 13 – 17 , 19 , 36 – 39 ). In these previous studies, although CD34 + hematopoietic stem cells were mobilized and isolated from HLA-mismatched donors and infused into the recipient, most researchers believed that the main functional anti-leukemia cells were T-cells, and donor CD3 + T-cells were found to interfere with survival after microtransplantation ( 38 , 40 ).…”

Clinical effect of decitabine in the treatment of myelodysplastic syndrome and influencing factors

“…It can reduce DNA methylation by inhibiting DNA methyltransferase, make the tumor suppressor gene return to normal, reactivate the gene inactivated due to DNA excessive methylation, and make the process of cell differentiation, aging or apoptosis return to normal. 16 , 17 A study of Ye et al enrolled 81 cases of MDS-RAEB, 18 40 patients were treated with decitabine before chemotherapy, and the median follow-up time was 10.9 months. Through comparing the results of chemotherapy alone with that of DAC before chemotherapy, it was found that the objective response rate (ORR) and CR rate of the decitabine group was significantly higher than that of chemotherapy group.…”

Comparison of Hypomethylator Monotherapy with Hypomethylator plus Chemotherapy for Intermediate/High-Risk MDS or AML: A Meta-Analysis

“…For the combination subgroup analysis, Studies using standard dose of intensive chemotherapy (DA, IA, etc.) [17][18][19][20] were classified as HMA + high-intensity subgroup, while those using reduced dose of intensive chemotherapy [21][22][23] were taken as HMA + low-intensity subgroup. Studies with compatible age and cytogenetic risk were first selected according to the median age.…”

“…The pooled CTCAE grade 3-4 infection rate was 66% (95%CI: 59%-73%) and 43% (95%CI: 0%-95%, P=0.000), and the pooled grade 3-4 cardiac rate was 12% (95%CI: 7%-16%) and 1% (95%CI: 0%-3%, P=0.000) for high and low-intensity subgroup, respectively. There was one study in each subgroup reporting grade 3-4 bleeding rate, which was 6% in high-intensity subgroup [17] and 28% for low-intensity subgroup [22].…”