Very Low-Dose Decitabine Is Effective in Treating Intermediate or High Risk Myelodysplastic Syndrome

Background: As an available hypomethylating agent, decitabine has significantly improved the outcome of patients with myelodysplastic syndrome (MDS). Nowadays the regular recommendation dose of decitabine is 20 mg/m²/d for five consecutive days with relatively high incidence of treatment related morbidities and costs. In this study, we aim to explore the efficacy and safety of very low-dose decitabine in the treatment of patients with MDS.

Methods: The clinical data of twenty-nine newly diagnosed consecutive MDS patients with IPSS intermediate-1-risk or above from fourteen hospitals in Beijing between Nov. 2015 to May. 2016 were collected retrospectively. Twenty-four patients received decitabine monotherapy (decitabine 7mg/m²/d for 7 days, repeated every 4 weeks), five patients received decitabine combined with decreased dose of CAG (Acla 10mg, d1-7; cytarabine 10mg q12h, d1-8; G-CSF150ug q12h, d1-14, repeated every 4-6 weeks). The overall response (ORR), complete remission (CR), partial response (PR) and hematologic improvement (HI) rate was evaluated. The safety profile and the treatment cost were documented. Factors affecting the efficacy were also analyzed in the end using the chi-square test or Fisher's exact test for categorical data and the Wilcoxon rank-sum test or the Student's t test for continuous data.

Results: Of the twenty-nine patients, twenty-one were males and eight were females. The median age was 63 years (36~85 years). Two patients (6.9%) were diagnosed as MDS-RCUD, three (10.3%) as MDS-RCMD, ten (34.5%) as MDS-RAEB1, and fourteen (48.3%) as MDS-RAEB2. At the end of follow-up time, the medium course was 2 (range 1-11 courses). Nine patients (31%) finished one course, seven patients (24.1%) finished two courses, five patients (17.2%) finished three courses, eight patients (27.4%) finished four or more courses. Ten patients achieved CR (34.5%), eight (27.6%) PR, one (3.4%) HI, eight (27.6%) stable disease (SD), two (6.8%) progress disease (PD) or death. The overall response rate (ORR) was 65.5%. Infection and bleeding rate were recorded in 44.9% of the courses, respectively, with 21.7% severe infections and 11.6% severe bleedings. Other side effects were rare and mild including unstable angina pectoris, vomiting, low serum albumin etc. (less than 2%). Two patients died, one died of cerebral hemorrhage within 30 days, and the other died of disease progression after 4 courses of treatment. The median cost of each course of treatment was 7.3 (1.4~28.4), 3.9(1.4~8.9), 3.1 (1.3~10.9), 2.6 (1.2~5.7) thousand dollars respectively. Nineteen patients who achieved at least HI (responders) were compared with the rest ten patients who did not benefit from the treatment (non-responders). Only difference in age (67.3±11.8 years for responders vs 56.1±11.9 years for non-responders, p=0.023) and proportion of bone marrow blast cells (10.8±4.9% for responders vs 5.8±5.3% for non-responders, p=0.016) was found between responders and non-responders, whereas no other differences were noticed between the two groups either in sex ratio (M:F 2.2:1 vs 4:1, p=0.675), high ECOG percentage (57.9% vs 20%, p=0.114), peripheral blood cell counts (hemoglobin 71 g/L vs 66 g/L, p=0.522; neutrophils 0.71 vs 0.6 × 10⁹/L, p=0.426; or platelet 33 vs 75 × 10⁹/L, p=0.218), percentage of adverse prognostic karyotypes (26.3% vs10% , P =0.633), or percent of intermediate -2 or high risk IPSS ( 68.4% vs 40%, p=0.236).

Conclusions: Verylow-dose decitabine alone or combined with decreased dose CAG regimen showed relatively good efficacy, well-tolerance and low medical cost in the treatment of intermediate or high risk MDS. Elderly patients or patients with a higher proportion of blast cells may be the better candidates for this regimen.