Single-unit unrelated cord blood transplantation versus HLA-matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry-based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.

Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs).

BACKGROUND: We sought to understand the clinical effectiveness associated with use of hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DEC) for patients with refractory anemia with excess blasts (RAEB; an established proxy for higher-risk myelodysplastic syndromes/neoplasms) in contemporary and representative real-world settings. PATIENTS AND METHODS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare database, a linkage of cancer registry and Medicare claims data, to identify patients aged ≥ 66 years diagnosed with RAEB, between 2009 and 2017 in the United States, and who received AZA or DEC as first-line therapy. Outcomes measured were overall survival (OS), event-free survival (EFS), and incidence of progression-related acute myeloid leukemia (AML). RESULTS: Of 973 eligible patients, 738 (75.8%) received AZA and 235 (24.2%) received DEC; 6.4% received hematopoietic cell transplantation during follow-up. In the overall population, median OS was 13.9 months (95% confidence interval [CI]: 12.9-15.0), median EFS was 5.2 months (95% CI: 4.9-5.7), and 38.0% of patients progressed to AML. Incidences of AML progression and death were 25.6% and 29.9%, respectively, at Year 1, and 34.3% and 44.8%, respectively, at Year 2. There were no significant differences in clinical benefits between AZA and DEC. CONCLUSION: Median OS with both HMAs remained significantly shorter than in the AZA-001 clinical trial, highlighting how patient outcomes vary between clinical and real-world settings. Further research is required to understand why these disparities exist.

Evaluation of in vitro rat and human airway epithelial models for acute inhalation toxicity testing.

In vivo models (mostly rodents) are currently accepted by regulatory authorities for assessing acute inhalation toxicity. Considerable efforts have been made in recent years to evaluate in vitro human airway epithelial models (HAEM) as replacements for in vivo testing. In the current work, an organotypic in vitro rat airway epithelial model (RAEM), rat EpiAirway, was developed and characterized to allow a direct comparison with the available HAEM, human EpiAirway, in order to address potential interspecies variability in responses to harmful agents. The rat and human models were evaluated in 2 independent laboratories with 14 reference chemicals, selected to cover a broad range of chemical structures and reactive groups, as well as known acute animal and human toxicity responses, in 3 replicate rounds of experiments. Toxicity endpoints included changes in tissue viability (MTT assay), epithelial barrier integrity (TEER, transepithelial electrical resistance), and tissue morphology (histopathology). The newly developed rat EpiAirway model produced reproducible results across all replicate experiments in both testing laboratories. Furthermore, a high level of concordance was observed between the RAEM and HAEM toxicity responses (determined by IC25) in both laboratories, with R2=0.78 and 0.88 when analyzed by TEER; and R2=0.92 for both when analyzed by MTT. These results indicate that rat and human airway epithelial tissues respond similarly to acute exposures to chemicals. The new in vitro RAEM will help extrapolate to in vivo rat toxicity responses and support screening as part of a 3Rs program.

The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial.

BACKGROUND: Relapse remains high in patients with myelodysplastic syndrome-refractory anaemia with excess blasts (RAEB) or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate whether granulocyte-colony stimulating factor (G-CSF) and decitabine plus busulfan-cyclophosphamide conditioning reduced relapse compared with busulfan-cyclophosphamide in this population. METHODS: We did an open-label, randomised, phase 3 trial at six hospitals in China. Eligible patients (aged 14-65 years) had myelodysplastic syndrome-RAEB or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome, and an Eastern Cooperative Oncology Group performance status of 0-2 and HSCT comorbidity index of 0-2. Patients were randomly assigned (1:1) to receive G-CSF, decitabine, and busulfan-cyclophosphamide conditioning or busulfan-cyclophosphamide conditioning. Randomisation was done with permuted blocks (block size four) with no stratification and was implemented through an interactive web-based response system, which was independent of study site staff and investigators. G-CSF, decitabine, and busulfan-cyclophosphamide conditioning comprised G-CSF 5 µg/kg daily subcutaneously (days -17 to -10), decitabine 20 mg/m2 daily intravenously (days -14 to -10), busulfan 3·2 mg/kg daily intravenously (days -7 to -4), and cyclophosphamide 60 mg/kg daily intravenously (days -3 and -2). Busulfan-cyclophosphamide conditioning comprised the same dose and duration of busulfan and cyclophosphamide. The primary endpoint was 2 year cumulative incidence of relapse. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02744742; the trial is complete. FINDINGS: Between April 18, 2016, and Sept 30, 2019, 297 patients were screened for eligibility, 202 of whom were randomly assigned to G-CSF, decitabine, and busulfan-cyclophosphamide (n=101) or busulfan-cyclophosphamide (n=101) conditioning. 123 (61%) participants were male and 79 (31%) were female. Median follow-up was 32·4 months (IQR 10·0-43·0). The 2-year cumulative incidence of relapse was 10·9% (95% CI 5·8-17·9) in the G-CSF, decitabine, and busulfan-cyclophosphamide group and 24·8% (16·8-33·5) in the busulfan-cyclophosphamide group (hazard ratio 0·39 [95% CI 0·19-0·79]; p=0·011). Within 100 days after transplantation, the most common grade 3-4 adverse events in the G-CSF, decitabine, and busulfan-cyclophosphamide group and the busulfan-cyclophosphamide group were infections (34 [34%] and 32 [32%]), acute graft-versus-host disease (30 [30%] and 30 [30%]), and gastrointestinal toxicity (28 [28%] and 29 [29%]). 11 (11%) patients in the G-CSF, decitabine, and busulfan-cyclophosphamide group and 13 (13%) in the busulfan-cyclophosphamide group died of adverse events. There were no treatment related deaths. INTERPRETATION: Our results suggest that G-CSF, decitabine, and busulfan-cyclophosphamide conditioning is a better choice than busulfan-cyclophosphamide conditioning for patients with myelodysplastic syndrome-RAEB or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic HSCT. This conditioning could be a suitable therapuetic option for this patient population. FUNDING: None. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prospective comparison of 5- and 7-day administration of azacitidine for myelodysplastic syndromes: a JALSG MDS212 trial.

The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T). However, this trial was prematurely terminated because of poor recruitment. Using all data, there was no significant difference in the OS of patients between AZA-7 (92 patients) and AZA-5 (95 patients), with the 2-year OS rates of AZA-7 and AZA-5 at 36.4% and 25.8%, respectively (P = 0.293). Adverse event profiles were similar between the two groups. Interestingly, data of the centrally diagnosed RAEB and RAEB-T cases showed that AZA-7 significantly prolonged the time to leukemia transformation compared with AZA-5 (P = 0.022), confirmed by multivariate analysis. Although this trial could not provide definite evidence, the results support the use of AZA-7 for RAEB and RAEB-T. (UMIN Clinical Trials Registry UMIN000009633).

Incidence and survival estimates for patients with myelodysplastic syndrome in the early 21st century: no evidence of improvement over time.

We examine changes in population level incidence and survival of patients diagnosed with myelodysplastic syndrome (MDS) in the United States in 2001-2016. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Period analysis was used to calculate one-, two-, and five-year survival. The incidence peaked at 5.6 per 100,000 in 2010 then decreased to 3.9 by 2016, with a decrease in the diagnoses of refractory anemia (RA) and RA with ringed sideroblasts (RARS) and a relative increase in RA with excess blasts (RAEB). Overall, one-, two-, and five-year relative survival decreased over time, going from 74.3%, 60.9%, and 42.3%, respectively, in 2008-2010 to 70.9%, 55.9%, and 37.6%, respectively, in 2014-2016. When survival was examined by histology, patients with RA/RARS and RAEB had similar survival expectations in 2008-2010 versus 2014-2016 and a decrease was observed for 5q-MDS. Our results highlight the need for new treatment options in MDS.

The WHO 2016 diagnostic criteria for Acute Myeloid leukemia with myelodysplasia related changes (AML-MRC) produce a very heterogeneous entity: A retrospective analysis of the FAB subtype RAEB-T.

We studied 79 patients with AML-MRC or RAEB-T, who were later reclassified according to the WHO classification. Marrow slides were examined cytomorphologically with regard to dysplasia. Patients were followed up until March 2020. Thirty-one patients underwent allogeneic stem cell transplantation (median survival (ms) 16 months), 14 were treated with induction chemotherapy (ms 8.4 months), 18 received hypomethylating agents (ms 9.2 months), 16 received low dose chemotherapy or best supportive care (ms 2.4 months). Only 30.4 % fulfilled the morphologic WHO criteria. 46.8 % were classified as AML-MRC by an antecedent MDS, 54.4 % of the pts were classified by MDS-related chromosomal abnormalities. 5 % did not fulfill any of the criteria and were entered based on 20-29 % medullary blasts. There was no difference in ms between pts presenting with > 50 % dysplasia as compared to pts with dysplasia between 10 % and 50 % (ms 9.1 vs 9.9 months, p = n.s.) or for pts with antecedent MDS (ms 9.1 vs 8.9 months, p = n.s.). Myelodysplasia-related cytogenetic abnormalities were associated with a worse outcome (ms 8.1 vs 13.5 months, p = 0.026). AML-MRC in its current definition is a heterogenous entity. Dysplasia of ≥ 50 % in ≥ two lineages is not helpful for diagnostics and prognostication and therefore should be deleted in future classifications. We recommend utilizing the WHO guidelines for defining dysplasia (10 % or greater in ≥ 1 of the three myeloid cell lines) assisting in establishing the diagnosis of MDS.

RAEB II type of myelodysplastic syndrome associated with axillary abscesses - Case Report.

Myelodysplastic syndromes (MDS) are clonal haematopoetic stem cells disorders, characterized by bone marrow dysplasia, ineffecitive haematopoesis and cytopenias. Due to neutropenia, infections are common. A case is presented of a patient with high-risk myelodysplastic syndrome (MDS) complicated by hidradenitis suppurativa that developed in both axillae. Abscesses required multiple incisions and drainage. After five cycles of treatment with azacitidine, the patient underwent allogenic bone marrow transplantation. Unfortunately, six months after the procedure, the patient lost post-transplant chimerism.Treatment with azacitidine was re-started. After the subsequent ten months, blast transformation was observed. Skin lesions in the course of hidradenitis suppurative persisted and were still considerably active.

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients.

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.

Under-use of Hypomethylating Agents in Patients With Higher-risk Myelodysplastic Syndrome in the United States: A Large Population-based Analysis.

BACKGROUND: Recent data suggest significant underutilization of hypomethylating agents (HMAs) that are recommended treatments for patients with myelodysplastic syndromes (MDS) with refractory anemia with excess blasts (RAEB). The study objective was to assess the degree of HMA use and predictors of HMA underuse in this population. PATIENTS AND METHODS: This was a retrospective study including patients diagnosed with the RAEB form of MDS between January 2011 and December 2015 using the Surveillance, Epidemiology, and End Results-Medicare linked database. Patients were excluded if they had < 1 year of continuous enrollment before diagnosis or received stem cell transplant or lenalidomide during the follow-up period. HMA non-peristence was defined as use of < 4 cycles (3-10 HMA days/28 days) of HMAs or a gap of ≥ 90 days between consecutive cycles. Patients were characterized as HMA never-users, HMA-persistent users, and HMA-non-persistent users. Descriptive statistics were used to summarize patient characteristics. Multivariable logistic regression was used to assess predictors of HMA underuse and persistence. RESULTS: Of the 1190 patients, 526 (44%) were never-users, 295 (25%) were non-persistent users, and 369 (31%) were persistent users. Age at diagnosis (eg, 66-70 years vs. ≥ 80 years; odds ratio [OR], 2.36; 95% confidence interval [CI], 1.56-3.56), marital status (single vs. married; OR, 0.67; 95% CI, 0.51-0.89), National Cancer Institute comorbidity index (≥ 3 vs. 0-1; OR, 0.62; 95% CI, 0.46-0.83), and performance status (poor vs. good; OR, 0.67; 95% CI, 0.51-0.87) were significantly associated with HMA underuse. CONCLUSION: Several demographic and clinical factors were associated with underuse of HMAs. There is need for a better understanding of suboptimal HMA use and its relationship with clinical response.

[Clinical Comparation of Two Kinds of Chemotherapy Regimens in the Treatment of Patients with MDS-RAEB/AML-MRC].

OBJECTIVE: To investigate the influence of conventional CAG regimen and decitabine + decreased dose CAG (D+dCAG) regimen on the clinical efficacy and safety of patients with MDS-RAEB/AML-MRC. METHODS: The clinical data of 67 patients with MDS-RAEB/AML-MRC hospitalized in our hospital from March 2012 to July 2017 were analyzed retrospectively. According to chemotherapecctic regimens, 76 patients were divided into 2 groups: 37 patients treated with conventional CAG regimen were enrolled in control group, 30 patients treated with decitabine + decreased dose CAG regimen were enrolled in D+dCAG group. The complete remission (CR) rate, overall remission rate (ORR), OS and PFS time and incidence of adverse reactions in 2 groups were compared. RESULTS: The CR in D+dCAG group was significantly higher than that in control group (P＜0.05). ORR was not significanly different between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate and PFS rate in nonimplantation between 2 groups (P＞0.05). The incidence of adverse reactions of hematological system, pulmonary infection, skin and soft tissue infection, agranulocytosic fever and mycotic infection was not significanly different between 2 groups (P＞0.05). The duration of granulocyte deficiency and platelet count less than 20×109/L were not significanly different between 2 groups (P＞0.05). CONCLUSION: Compared with conventional CAG regimen, decitabine + decreased dose CAG regimen in the treatment of patients with MDS-RAEB/AML-MRC can efficiently improve the remission effects and showed the well overall safety, but can not increase the survival rate.

Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial.

Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m2 daily, days 1 to 3; idarubicin, 6 mg/m2 daily, days 4 to 6; cytarabine 25 mg/m2 every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 µg/kg, from day 4 until neutrophil count increased to 1.0 × 109 /L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2.

SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS.

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.

Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†.

Hypomethylating agents (HMA) showed overall survival (OS) benefits in patients with higher-risk myelodysplastic syndromes (HR-MDS) in clinical trials. We conducted a retrospective cohort study of Surveillance, Epidemiology, and End Results (SEER)-Medicare data of patients ≥66 years diagnosed with refractory anemia with excess blasts (RAEB), a proxy for HR-MDS, in 01/2001-04/2004 (pre-period) or 01/2006-12/2011 (post-period). Association between post-period diagnosis and OS was examined using propensity scores (PS)-matched samples. Among 1876 RAEB patients, median OS was 9 months and 30.8% received HMAs (3.6% in pre-period; 43.0% in post-period) with no association between post-period diagnosis and OS. In the top PS quartile, post-period diagnosis was associated with a 74% lower risk of death (Hazard ratio [HR] = 0.26, 95%-CI: 0.10-0.69, p = 0.007), while outcomes were worse in the lowest PS quartile (HR = 2.80, 95%-CI: 1.06-7.36, p = 0.037). HMA lead to a 3-month OS benefit for patients most likely to receive HMA but not for unselected RAEB cohort.

Clinical Comparation of Two Kinds of Chemotherapy Regimens in the Treatment of Patients with MDS-RAEB/AML-MRC / 中国实验血液学杂志

OBJECTIVE@#To investigate the influence of conventional CAG regimen and decitabine + decreased dose CAG (D+dCAG) regimen on the clinical efficacy and safety of patients with MDS-RAEB/AML-MRC.@*METHODS@#The clinical data of 67 patients with MDS-RAEB/AML-MRC hospitalized in our hospital from March 2012 to July 2017 were analyzed retrospectively. According to chemotherapecctic regimens, 76 patients were divided into 2 groups: 37 patients treated with conventional CAG regimen were enrolled in control group, 30 patients treated with decitabine + decreased dose CAG regimen were enrolled in D+dCAG group. The complete remission (CR) rate, overall remission rate (ORR), OS and PFS time and incidence of adverse reactions in 2 groups were compared.@*RESULTS@#The CR in D+dCAG group was significantly higher than that in control group (P＜0.05). ORR was not significanly different between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate and PFS rate in nonimplantation between 2 groups (P＞0.05). The incidence of adverse reactions of hematological system, pulmonary infection, skin and soft tissue infection, agranulocytosic fever and mycotic infection was not significanly different between 2 groups (P＞0.05). The duration of granulocyte deficiency and platelet count less than 20×10/L were not significanly different between 2 groups (P＞0.05).@*CONCLUSION@#Compared with conventional CAG regimen, decitabine + decreased dose CAG regimen in the treatment of patients with MDS-RAEB/AML-MRC can efficiently improve the remission effects and showed the well overall safety, but can not increase the survival rate.

[Comparation of Clinical Efficacy between Two Regimens of Preexcitation Chemotherapy for MDS-RAEB Patients].

OBJECTIVE: To investigate the efficacy and safely of DAC and CAG/HAG preexcitation chemotherapy regimens for the treatment of patients with MDS-RAEB (refractory anemia with excess blasts, RAEB). METHODS: The clinical data of 86 MDS-RAEB patients were analyzed retrospectively from February 2014 to February 2018. According to therapeutic regimem, the 86 patients were divided into 2 groups: group A (41 patients) with DAC preexcitation chemotherapy regimen, and group B (45 patients) with CAG/HAG preexcitation chemotherapy regimen; and the disease control effect, effective treatment course, median survival time and incidence of adverse reactions were compared between these 2 groups. RESULTS: The CR rate and ORR rate were not significantly different between these 2 groups (P＞0.05). The mCR rate in group A was significantly higher than that in group B (P＜0.05). The numbers of cases obtained therapeutic efficacy at 2 rd and 3 rd conrse in group A significantly more than those in group B (P＜0.05), but the number of cases obtained efficacy at 1 st course in group B was significantly higher than that in group A (P＜0.05). The median OS time was not significanly different between 2 groups (P＞0.05). The duration of neutrophils deficiency in group A was significantly shorter than that in group B (P＜0.05). The transfusion volume of red blood cells and platelets in group A was significantly less than that of group B (P＜0.05). The incidence of neutropenia, anemia and thrombocytopenia of III-IV grade at different treatment courses of group A were significantly lower than that in group B (P＜0.05). The incidence of infection of III-IV grade in group A at 3rd treatment course was significantly lower than that in group B (P＜0.05). CONCLUSION: Preexcitation chemotherapy regimens of DAC and CAG/HAG for the treatment of MDS-RAEB possess the same effects for disease control; application of DAC regimen can efficiently reduce the risk of adverse reaction, but CAG/HAG regimen can be helpful to accelerate the effective process of treatment.

Decitabine improves overall survival in myelodysplastic syndromes-RAEB patients aged ≥60 years and has lower toxicities: Comparison with low-dose chemotherapy.

Decitabine and low-dose chemotherapy are common treatments for intermediate and high risk myelodysplastic syndromes (MDS). In this study, we retrospectively assessed the efficacy and toxicity of the two regimens for MDS-refractory anemia with excess blasts (MDS-RAEB) patients. A total of 112 patients with a diagnosis of MDS-RAEB are included. The overall response (OR) and complete remission (CR) rate was comparable between the two groups (OR: 64.1% vs. 66.7%, p = 0.60; CR: 23.4% vs. 31.3%, p = 0.64). The OR rates of 20 mg/m2/day and 15 mg/m2/day decitabine regimen were comparable (69.0% vs. 60.0%, p = 0.46). Overall survival (OS) did not differ significantly between the groups (20.7 vs. 13.5 months, p = 0.17). In a subgroup analysis that included only patients at ≥60 years of age, survival benefit of decitabine was apparent (20.6 vs. 10.0 months, p = 0.03). In hematological toxicities, the lowest count of platelet in the decitabine group was higher significantly. And, the incidence of Grade 3-4 infection in the decitabine group was lower significantly. Our results demonstrate that both decitabine and low-dose chemotherapy are effective for MDS-RAEB, but decitabine was safer. Decitabine might be a better choice for patients at ≥60 years of age.