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

PURPOSE: This study was undertaken to investigate the clinical characteristics and prognostic predictors of myelodysplastic syndrome (MDS) in childhood. Method: The characteristics and laboratory findings of 20 patients seen at Asan Medical Center for the past 10 years from September 1989 to August 1998 were reviewed retrospectively with regard to the new International Prognostic Scoring System (IPSS) proposed by International MDS Risk Analysis Workshop. RESULTS: 1) In 20 children with MDS we studied, there was no age or sex predilection unique to the subgroups of MDS. 2) 19 cases (95%) out of the 20 had pallor at the time of diagnosis. Other major clinical findings were bleeding tendency in 11 (55%), fever in 8 (40%), hepatosplenomegaly in 8 (40%), and lymphadenopathy in 3 (15%). 3) The hemoglobin level was less than 10 g/dL in all cases and absolute neutrophil count (ANC) was decreased in 11 cases, thrombocytopenia in 15 cases. Pancytopenia was noted in 8 cases (40%). 4) Of the 20 cases, 9 had refractory anemia (RA), 3 refractory anemia with excess blasts (RAEB), 3 refractory anemia with excess blasts in transformation (RAEBIT), and 5 juvenile chronic myelogenous leukemia (JCML). 5) All RA patients were Intermediate (INT)-1 risk group, and all RAEB children were INT-2 risk group. The 3 cases of RAEBIT fell into INT-1, INT-2, and high risk group. Three cases of JCML were INT-1 group, and 2 cases INT-2 group. 6) Seven cases out of 13 INT-1 group had mean survival of 20.2 month (6~57 month), but only 1 out of 6 INT-2 survived. One case of high risk group succumbed to disease 50 months after diagnosis. CONCLUSION: These results showed that there was no age or sex predilection for the specific subgroup of childhood MDS. All the FAB subtypes of the childhood MDS except RA subgroup had poor survival. In this study, we found the IPSS seemed to be a prognostic predictor in childhood MDS but more cases are needed to confirm the validity of IPSS.
Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; Child ; Chungcheongnam-do ; Diagnosis ; Education ; Fever ; Hemorrhage ; Humans ; Leukemia, Myelomonocytic, Juvenile ; Lymphatic Diseases ; Myelodysplastic Syndromes* ; Neutrophils ; Pallor ; Pancytopenia ; Prognosis ; Retrospective Studies ; Thrombocytopenia

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

BACKGROUND: Several studies about myelodysplastic syndromes (MDS) have demonstrated that patients with high score of erythrocytic and total dysplasia showed a significantly lower degree of acute myeloid leukemia (AML) development. We analyzed correlation between bone marrow dysplasia and peripheral blood indices, and estimated the value of peripheral blood indices substituted for bone marrow examination to predict the progress of MDS to AML. METHODS: RBC count, MCV, RDW, WBC count, platelet count, MPV, and PDW were measured by Coulter Counter STKS (USA). We calculated the granulation score (G-score), percentage of peudo-pelger polymorphs (PPP) in the peripheral blood film, and examined the dysplasia in bone marrow aspirates. The reticulocyte survival study was performed with the venous blood collected in CPDA-1 under sterile conditions which was incubated immediately after collection at 37degrees C. RESULTS: G-score was inversly correlated with granulocytic and total dysplasia, but highly scored PPP showed a significantly lower degree granulocytic and total dysplasia. Reticulocyte survival curves showed variable pattern according to degree of erythrocytic and total dysplasia. Patients with a high degree of erythrocytic and total dysplasia showed significant difference compared with normal control group. MPV was increased in accordance with increase in megakaryocytic and total dysplasia. A lower score for erythrocytic and total dysplasia was observed in RAEB-t than in RA and RAEB. CONCLUSIONS: It is suggested that G-score, PPP, and MPV in peripheral blood as well as reticulocyte survival curve may be good markers for bone marrow dysplasia, and erythrocytic and total dysplasia in RAEB-t is lower than in RA and RAEB. Therefore, peripheral blood indices can be used to predict the progress of MDS to AML
Anemia, Refractory, with Excess of Blasts ; Bone Marrow Examination ; Bone Marrow* ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes* ; Platelet Count ; Reticulocytes

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

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

BACKGROUND: The myelodysplastic syndromes (MDS) in childhood is considered to be very rare and the nature of this disease in childhood is very different from that in adults. We analyzed the hematologic findings of childhood myelodysplastic syndrome. METHODS: The retrospective study was performed with the confirmed patients who were admitted to the Department of Pediatrics, Asan Medical Center (AMC) from June 1989 till May 1999, to analyze the hematologic findings. Sixteen children with a primary myelodysplastic syndrome (MDS) were presented to AMC during a 10 year period. RESULTS: Morphological assessment of the peripheral blood and the bone marrow showed nine patients (56%) had refractory anemia (RA), two patients (13%) had RA with excess blasts (RAEB), five patients (31%) had RAEB in transformation (RAEB-t). Five children with juvenile chronic myelogenous leukemia were diagnosed over the same period. Age distribution showed the predilection between 6~10 years and male : female ratio was 1 : 1. Inperipheralblood, pancytopenia was found in seven cases (44%) and leukocytosis in four cases (25%). The bone marrow findings showed hypercellularity in 54%, hypocellularity in 8% and variable cellularity in 15% and myelofibrosis was observed in 23%. Various dyspoietic changes of erythrocytes, leuko- cytes and platelets in peripheral blood and three cell lines in bone marrow were observed and trilineage dysplasia was observed in 62% of MDS, and 56% of RA. The four cases (25%) of RAEB and RAEB-t have transformed to acute myelogenous leukemia. CONCLUSION: In our study, the MDS in childhood seemed to be characterized by higher incidence of RA. Compared with the adult MDS, trilineage dysplasia in RA was frequently seen, but, no significant differences of dyspoietic features between adults and childhood were observed.
Adult ; Age Distribution ; Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; Cell Line ; Child ; Chungcheongnam-do ; Erythrocytes ; Female ; Humans ; Incidence ; Leukemia, Myeloid, Acute ; Leukemia, Myelomonocytic, Juvenile ; Leukocytosis ; Male ; Myelodysplastic Syndromes* ; Pancytopenia ; Pediatrics ; Primary Myelofibrosis ; Retrospective Studies

BACKGROUND: Soluble IL-2R, soluble CD8 and TNF-alpha are elevated in sera of some patients with hematological malignancies, and a marked elevation of these cytokines could be used to assess disease activity and prognosis in this malignancy group. METHODS: The serum levels of sIL-2R, sCD8 and TNF-alpha were assessed in 28 patients with myelodysplastic syndrome (MDS) and 32 patients with acute myeloid leukemia (AML), and 39 cases of healthy control subjects to define clinical usefulness as prognostic markers by sandwich enzyme immunoassay. RESULTS: In MDS patients, serum sIL-2R levels were significantly higher as compared with controls, and a more pronounced increase of serum sIL-2R levels was found in patients with RAEB RAEB-t and CMML as compared with RA and RARS. Serum sCD8 levels were higher as compared with controls, but not related with FAB classification. In patients with leukemic conversion. sCD8 levels tended to be higher as compared with patients with non-conversion. The sIL-2R levels of AML patients were significantly higher than controls, and a significant correlation was detected between the levels of sIL-2R and WBC counts. Higher sIL-2R levels( >2000 U/ml) tended to affect both complete remission rate and survival. Serum sCD8 levels were higher than controls, but not related to FAB classification. No differences of serum TNF-alpha levels were detected as compared with healthy controls. CONCLUSIONS: From these results, this study indicates that serum sIL-2R and sCD8 are significantly increased in some patients with MDS and AML, and increased levels of serum sIL-2R and sCD8 may be useful for predicting prognosis of these patients.
Anemia, Refractory, with Excess of Blasts ; Classification ; Cytokines ; Hematologic Neoplasms ; Humans ; Immunoenzyme Techniques ; Leukemia, Myeloid, Acute* ; Myelodysplastic Syndromes* ; Prognosis ; Tumor Necrosis Factor-alpha*

BACKGROUND: World Health Organization (WHO) proposed a new classification of myelodysplastic syndrome (MDS) in 1999, based on significant modifications of the original FAB proposals. The aim of the present study was to validate the new classification with respect to prognostic importance. METHODS: Two hundred and eighteen patients were diagnosed with MDS according to the FAB criteria between August 1989 and June 2001 in the Asan Medical Center. They were studied retrospectively to evaluate morphological, clinical and cytogenetic data for diagnosis and clinical outcomes with long-term follow up, and reclassified with a new WHO classification. RESULTS: According to the original FAB classification, 218 patients were classified as RA 78, RARS 17, RAEB 76, RAEB-t 38 and CMML 9. They were reclassified to the WHO classification to RA 24, RARS 6, RCMD 51, RCMD-RS 11, RAEB-1 42, RAEB-2 51, del(5q) syndrome 1 and unclassifiable 2. Twenty-one cases of RAEB-t and 9 cases of CMML were reclassified to acute myeloid leukemia and myelodysplastic syndrome/myeloproliferative disease (MDS/MPD). Among the reclassified groups in the WHO classification, there is a significant difference in prognosis between RA and RCMD (median survival, not reached vs. 28.4 months, P=0.020), and in leukemic transformation between RAEB-1 and RAEB-2 (5% vs. 37%, P=0.001). CONCLUSIONS: These data provide the proper evidence, especially of prognosis and leukemic transformation for the WHO classifications. We recommended using the WHO classification rather than the FAB classification of the diagnosis of MDS.
Anemia, Refractory, with Excess of Blasts ; Chungcheongnam-do ; Classification* ; Cytogenetics ; Diagnosis ; Follow-Up Studies ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes* ; Prognosis ; Retrospective Studies ; World Health Organization

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