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.
Anemia, Refractory, with Excess of Blasts ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Decitabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Retrospective Studies ; Treatment Outcome

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.
Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; drug therapy ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis.

METHODSR- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.

RESULTSOf 672 cases of patients with MDS, chromosome 1 aberration［der（1）, dup（1）, －1 were most frequent］ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.

CONCLUSIONChromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.

Abnormal Karyotype ; Acute Disease ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; China ; Chromosome Aberrations ; Chromosome Banding ; Chromosomes, Human, Pair 1 ; genetics ; Humans ; Karyotyping ; Leukemia ; diagnosis ; genetics ; Myelodysplastic Syndromes ; diagnosis ; genetics ; Prognosis ; Risk Factors ; Trisomy

Anemia, Refractory, with Excess of Blasts ; complications ; drug therapy ; Azacitidine ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; complications ; drug therapy ; Treatment Outcome

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.
Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; Cell Cycle ; Disease Progression ; DNA Methylation ; Epigenomics ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; Methylation ; Myelodysplastic Syndromes ; Polymerase Chain Reaction ; Prognosis

Bullous pemphigoid (BP) has a recognized association with solid organ tumors, but is relatively rare in hematological malignancies. We report a 67-year-old male who developed BP after being diagnosed with myelodysplastic syndrome and refractory anemia with excess of blast (RAEB). Skin biopsy elucidated sub-epidermal bulla using direct immunofluorescence, revealing linear C3 and IgG deposits along the basement membrane. His BP was recalcitrant to the conventional treatment and only responded to a combination of high dose oral prednisolone and azathioprine. The relative refractory nature of his condition and concurrent RAEB supports a paraneoplastic nature.
Aged ; Anemia ; Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; Azathioprine ; Basement Membrane ; Biopsy ; Blister ; Fluorescent Antibody Technique, Direct ; Hematologic Neoplasms ; Humans ; Immunoglobulin G ; Male ; Myelodysplastic Syndromes ; Paraneoplastic Syndromes ; Pemphigoid, Bullous ; Prednisolone ; Skin

OBJECTIVETo explore the efficiency and side-effects of the combination of cyclosporine A (CsA) and thalidomide in patients with myelodysplastic syndromes (MDS).

METHODSA total of thirty-seven patients with MDS-RCMD or-RAEB-I were treated with CsA in combination with thalidomide. The initial CsA dose of 3 mg×kg(-1)×d(-1) was administered, all patients had their CsA blood concentration concurrently monitored until it reached and maintained between 100 and 200 µg/L. The initial dose of thalidomide was 50 mg/d, with increasing dose of 50 mg every week until the maximum of 200 mg/d. The hematological response was assessed according to the modified criteria of the International Working Group, and adverse events were graded with the Common Toxicity Criteria (v3.0) of the National Cancer Institute. The response duration and overall survival of the patients were also observed.

RESULTS19/37 cases (51.4%) achieved hematologic improvement (HI)-erythroid response (HI-E), 9/29 cases (31.0%) HI-platelet response (HI-P) and 7/33 cases (21.2%) HI-neutrophil response (HI-N). 15 of 32 transfusion-dependent patients (46.9%) achieved transfusion independence. The median response duration of HI-E, HI-P and HI-N were 88 (4 - 88) weeks, 78 (8 - 84(+)) weeks and 78 (10 - 84(+)) weeks respectively. The median overall survival was 52 months on a 29 (4 - 103) months median follow-up. Some patients developed grades I-II hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rashes or numbness, and all were tolerable and reversible. No grade III or severer adverse events were observed.

CONCLUSIONCsA in combination with thalidomide appears to be effective mainly in inducing HI-E and relatively well-tolerated for the treatment of patients with MDS.

Anemia, Refractory, with Excess of Blasts ; drug therapy ; Cyclosporine ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Thalidomide ; therapeutic use ; Treatment Outcome

OBJECTIVETo screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling.

METHODSThe serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching.

RESULTSSeven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein.

CONCLUSION2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.

Anemia, Refractory, with Excess of Blasts ; blood ; genetics ; Bone Marrow ; pathology ; DNA-Directed DNA Polymerase ; blood ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ; blood ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; classification ; genetics ; Proteomics

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematologic stem cell disorders characterized clinically and morphologically by ineffective hematopoiesis. A consensus-defined French-American-British (FAB) classification and International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. So we investigate clinical characteristics and prognosis of MDS, according to French-American-British (FAB) classification and International Prognostic Scoring System (IPSS). METHODS: A retrospective analysis of 50 patients who were diagnosed as myelodysplastic syndrome at Ajou University Hospital was performed from November, 1994 to April, 2003. The patients with secondary MDS were excluded. All patients were classified according to the FAB classification and calculated prognostic scores for IPSS. Patients were evaluated for clinical features and for blood and bone marrow findings at the time of diagnosis, and were followed up for survival and leukemic progression. Survival curves were based on the Kaplan-Meier method. All reported p values less than or equal to 0.05 were regarded as stastistically significant. RESULTS: The peak age was in the fifth decade and the male to female ratio was 1.5:1. RA (36%) was observed most frequently. Thereafter, RAEB-t (26%), RAEB (24%), RARS (12%) and CMML (2%) were observed, respectively. The initial symptoms on admission were fever (24%), dizziness and headache (16%), general weakness (16%), hemorrhage (14%), dyspnea (12%), abdominal pain (4%) and vomiting (4%). Cytogenetic studies were performed in 34 patients with MDS. They were classified as good, intermediate, poor group by chromosome score of IPSS. The median survival was 16.4 months for the good group, 15 months for the intermediate, 10.3 months for the poor. The median survival according to FAB classified groups were RA (33.8 mo), RARS (12.5 mo), RAEB (16.4 mo), RAEB-t (6.7 mo) and CMML (1.3 mo). Survival according to IPSS scoring system were 67.2 months for low, 27.1 months for intermediate-1, 10.3 months for intermediate-2 and 6.0 months for high groups. These data were statistically significant (p<0.05). CONCLUSIONS: In our experiencies, FAB and IPSS classification would be good predictors in clinical outcomes. But, because of the heterogeneity of MDS, large multicenter studies will be needed to define the issue of a new classification for these disorders.
Abdominal Pain ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; Classification* ; Cytogenetics ; Diagnosis ; Dizziness ; Dyspnea ; Female ; Fever ; Headache ; Hematopoiesis ; Hemorrhage ; Humans ; Male ; Myelodysplastic Syndromes* ; Population Characteristics ; Prognosis* ; Retrospective Studies ; Stem Cells ; Vomiting

BACKGROUNDThe inhibitor of apoptosis (IAP) gene family is involved in the suppression of apoptotic cell death as well as an increasing number of seemingly unrelated cellular functions. It is not known, however, whether IAP expression in malignant hematopoietic cells is affected by chemotherapeutic agents such as homoharringtonine (HHT). In this study, we investigated mRNA expression levels of IAPs, especially survivin, in various hematopoietic cell lines in relation with apoptosis induced by HHT.

METHODSSemiquantitative reverse transcriptase polymerase chain reaction was used to determine survivin mRNA levels. Cell apoptosis was examined by flow cytometry. Cell viability and proliferation assay was evaluated by MTT. The experiments were performed on the malignant hematopoietic cell lines MUTZ-1, K562, Jurkat, RMPI and HL60, with or without survivin antisense-oligodeoxynucleotides (AS-ODN) and HHT.

RESULTSThe expression levels of survivin mRNA were variable in the cell lines and negatively correlated to HHT induced cell apoptosis. Survivin AS-ODN significantly decreased mRNA level of survivin, but not those of bax and bcl-2. Survivin also inhibited MUTZ-1 cell growth and induced apoptosis in a dose dependent manner. AS-ODN and HHT showed synergistic effect on MUTZ-1 cell growth.

CONCLUSIONThe apoptotic effect of HHT on the hematopoietic cell lines is associated with decreased level of survivin expression. Survivin could be a new marker for drug sensitivity and a new target for cancer treatment.

Anemia, Refractory, with Excess of Blasts ; metabolism ; pathology ; Apoptosis ; drug effects ; Cell Cycle ; Cell Line ; Harringtonines ; pharmacology ; Humans ; Inhibitor of Apoptosis Proteins ; Leukemia ; metabolism ; pathology ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; Oligonucleotides, Antisense ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; RNA, Messenger ; analysis ; bcl-2-Associated X Protein