Incidence of myelodysplastic syndromes in a Swedish population

Abstract: The myelodysplastic syndromes (MDS) have attracted great interest during the last decade. Unfortunately there is not much material published concerning the incidence of these conditions. We present epidemiologic data on MDS based on case registration of patients in a well-defined population and as a comparison similar data on acute myeloid leukaemia (AML). Between the years 1978–1992 we registered 120 cases of MDS and 146 cases of AML. The median age for all the MDS cases was 74.1 years for men and 78.2 years for women. Among haematologists there is a suspicion that the incidence of MDS is rising. Our study does not support this opinion. We have divided the study period into 5-year periods and the crude incidence has been 3.2, 4.1 and 3.5/100 000/year for each period. In the age group over 70 years MDS was more frequent than AML and in the last 5-year period the incidence was 15.0/100 000/year for MDS compared to 10.2/100 000/year for AML. In conclusion MDS is quite common among elderly people and there is no evidence for a rising incidence during the last 15 years.     

Incidence of congenital heart disease in navarra (1989-1998)

INTRODUCTION AND OBJECTIVES: Congenital cardiopathies are the most common forms of congenital malformation. They occur in between 5.2 and 12.5 in every thousand live births. The aim of this study was to describe the incidence and nature of congenital heart disease in the Spanish region of Navarra during a specified time period (1989-1998). PATIENTS AND METHOD: The study involved all children with congenital heart disease among the 47 783 born in the region in the specified time period. RESULTS: The incidence was 8.96 per thousand live births, with 90% having one of the 10 most common types of cardiac malformation. The accumulative percentage diagnosed was 25.3% in the first 24 hours of life, 45% in the first week, 65% in the first month, and 83.1% during the first year. Some 30.8% of cases of congenital heart disease required invasive treatment: 25.4% underwent surgery and 6.4%, cardiac catheterization. CONCLUSIONS: The incidence of congenital heart disease in Navarra falls within the range reported for developed countries. The level of care provided in this region is good, as demonstrated by existing diagnostic capabilities and treatment provision.     

Incidence and characterization of secondary myelodysplastic syndromes following autologous transplantation

BACKGROUND AND OBJECTIVE: Secondary myelodysplastic syndromes (sMDS) and secondary acute myeloid leukemias (sAML) have been observed after conventional chemo/radiotherapy and autologous hematopoietic stem cell transplantation. The aim of the present study was to analyze Spanish experience regarding the incidence and characteristics of sMDS and sAML following autologous transplantation. DESIGN AND METHODS: We obtained information from 7 institutions which perform autologous transplantation in Spain. Data from 1,081 and 1,411 patients who had received allogeneic and autologous transplantation, respectively, were available. RESULTS: None of the allografted patients had developed a sMDS/sAML so far. Thirteen cases of sMDS/sAML following autologous transplantation were reported. The mean age of these 13 patients at the time of transplantation was 40 years (range 16-58). Five had non-Hodgkin's lymphoma, 6 had Hodgkin's disease, 1 had acute myeloblastic leukemia and 1 had multiple myeloma. The crude overall incidence of sMDS/sAML was 0.9%. The incidence did not differ according to the source of progenitor cells (1% and 0.8% for bone marrow and peripheral blood, respectively). Cytogenetic analysis showed clonal abnormalities in 11 of the 13 cases. Patients with sMDS/sAML had received more doses of alkylating agents than non-sMDS patients (p = 0.0015). The median time between transplantation and diagnosis of sMDS/sAML was 28 months (range 1.5-63). This time was significantly longer for patients who received bone marrow than for those who received peripheral blood (45 versus 18 months, p = 0.01). Median overall survival after diagnosis of sMDS/sAML was 13 months. INTERPRETATION AND CONCLUSIONS: The crude incidence of sMDS/sAML in our series was similar to other published incidences. We did not find any difference in incidence between patients who had received bone marrow or peripheral blood; however, the medi an time elapsed between transplantation and sMDS diagnosis was shorter when peripheral blood was infused. Higher doses of alkylating agents were associated with the appearance of sMDS/AML.     

Correlations between cytogenetics and morphology in myelodysplastic syndromes

Summary In order to detect possible relationships between cytogenetic abnormalities and morphologic features in myelodysplastic syndromes (MDS), 48 patients with MDS were investigated. Clonal cytogenetic abnormalities were present in bone marrow cells from 27 patients (56%). The most frequent single anomaly was del (5 q) (10 cases), followed by monosomy 7 (3 cases), trisomy 8 (3 cases) and del (20 q) (2 cases). Complex anomalies were present in 6 patients. Morphologically, according to the French-American-British (FAB) classification: 17 cases were considered as refractory anemia (RA), 17 as RA with excess of blasts (RAEB), 2 as RAEB in transformation, 2 as acquired idiopathic sideroblastic anemia and 10 as chronic myelomonocytic leukemia. With regard to the FAB classification, del (5 q) was often associated with RA and complex cytogenetic anomalies with RAEB. When myelodysplasia was studied in individual myeloid lineages, del (5 q) was associated with hypolobulated megakaryocytes, monosomy 7 with micromegakaryocytes and complex chromosomal anomalies with the association of two or more features of dysmegakaryocytopoiesis. Del (11 q) was associated with increased iron storage and del (20 q) with marked dyserythropoiesis. No correlation was observed between cytogenetic anomalies and features of dysgranulocytopoiesis.     

细胞凋亡与骨髓增生异常综合征疾病演变的关系

目的探讨骨髓增生异常综合征（ＭＤＳ）骨髓细胞凋亡特征及其病理学意义。方法用原位末端脱氧核糖核苷酸转移酶介导的ｄＵＴＰ缺口末端标记（ＴＵＮＥＬ），ＤＮＡ梯子和体外培养等方法对３８例ＭＤＳ患者骨髓单个核细胞（ＢＭＭＣ）凋亡进行研究。结果ＭＤＳ患者ＢＭＭＣ的ＴＵＮＥＬ凋亡细胞阳性指数（ＰＩ）为２０．１９％±１１．０７％，显著高于正常人、ＭＤＳ转化的白血病、急性髓细胞白血病（ＡＭＬ）及缺铁性贫血（ＩＤＡ）组，（Ｐ＜０．００１和Ｐ＜０．０１）。ＴＵＮＥＬ和ＣＤ４１碱性磷酸酶抗碱性磷酸酶免疫酶标法（ＡＰＡＡＰ）双标记证明ＭＤＳ骨髓病态小巨核细胞发生了凋亡。动态观察１０例ＭＤＳ患者，转为白血病后凋亡细胞ＰＩ值显著下降，尚未转为白血病患者随病情恶化凋亡呈下降趋势。７例ＭＤＳ患者ＢＭＭＣ体外培养后，晚期ＰＩ（ＬＰＩ）显著增高，３例出现ＤＮＡ梯子，ＡＭＬ和ＩＤＡ组ＬＰＩ未见明显升高，未出现ＤＮＡ梯子。结论ＭＤＳ骨髓细胞凋亡过度与演变和转为白血病有关。原位检测细胞凋亡可作为监测ＭＤＳ预后指标     

Incidence of ATRX mutations in myelodysplastic syndromes,the value of microcytosis

Acquired α‐thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy. Our data confirm the low frequency of ATRX mutations in MDS: 0% in an unselected clinical trial cohort of 80 low risk MDS, 0.2–0.8% in a multicenter registry of 2,980 MDS and 43% of MDS with unexplained microcytosis in this same registry. In addition, we reported four novel mutations of the ATRX gene in ATMDS. This study further determines the frequency of ATRX mutations and highlights the importance of microcytosis to detect ATRX mutations within MDS patients. Am. J. Hematol. 90:737–738, 2015. © 2015 Wiley Periodicals, Inc.     

Hypocellular myelodysplastic syndromes (MDS): new proposals

Summary. To determine whether hypocellular MDS differs from normo/hypercellular MDS, we attempted to identify hypocellular MDS cases either by correcting the bone marrow (BM) cellularity by age (28 patients) or by using a single arbitrary value of BM cellularity (25 patients) and compared these two groups of hypocellular cases to the normo/hypercellular MDS cases (72 patients). 18 patients were common to both hypocellular groups. Patients with hypocellular MDS in both of these selected groups have similar features with regard to age and sex distribution, peripheral blood and bone marrow parameters, FAB subtypes, karyotypes, leukaemic transformation, and survival. However, the median age of patients in < 30% BM cellularity group was higher than those patients in the age-corrected group (69 years v 62 years). The selection of < 30% cellularity excluded 10 cases in the age group < 70 years but included another seven patients in the age group of > 70 years. However, correction of BM cellularity by age revealed that those included patients (selected for < 30% cellularity) who had normocellular BM by their age. Therefore we recommend the age-correcting grouping to ensure comparable series for comparison, for response to treatment, and survival. Finally, BM cellularity does not appear to be an important factor on prognosis in MDS, because patients with hypocellular MDS in both selected groups have similar prognosis to those with normo/hypercellular MDS patients.     

Spanish production of research articles on diagnostic imaging in cardiology and radiology (1994-1998)

INTRODUCTION AND OBJECTIVES: The aim of this study was to evaluate the production of research papers by Spanish authors on diagnostic imaging published in the official journals of two Spanish scientific societies (Revista Espa?ola de Cardiología and Radiología) between 1994 and 1998, and to compare publication rates with those of research papers published in foreign cardiological and radiological journals included in Journal Citation Reports. MATERIAL AND METHOD: Specific search profiles were devised to retrieve items from the Indice Médico Espa?ol (IME) and MEDLINE databases. The impact factor for non-Spanish journals devoted to different specialties was normalized for the number of papers published. RESULTS: 967 articles were analyzed (301 on cardiac imaging, 666 on radiology). In the former specialty, 50.5% of the items were published in Revista Espa?ola de Cardiología, and in the latter, 55.1% were published in Radiología (no statistically significant difference). Impact factor was 2.46 for cardiology and 0.98 for radiology. The percentage of papers published in journals ranked in the top quartile according to impact factor was 38.6% (cardiology) and 17.2% (radiology); the difference was significant at P< .0001. DISCUSSION: Although a tendency for radiologists to publish increasingly in foreign radiological journals has been observed, Spanish cardiologists and radiologists publish more than 50% of their research papers on diagnostic imaging in the official journals of their national societies. The differences in the percentage of articles by Spanish authors published in international specialty journals ranked in the first quartile (twice as great for cardiology as for radiology) suggests that Spanish radiologists are joining the scientific international community at a slower rate than Spanish cardiologists.     

Low dose cytosine arabinoside (Ara C) in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are acquired bone-marrow disorders, characterized by a decreased ability of the haemopoietic cell to differentiate, resulting in peripheral cytopenias. The majority of patients will die either from acute myeloid leukaemia or from infection and/or haemorrhage. Thirty-eight courses of low dose Ara C were administered in 26 MDS patients. Nineteen courses (50%) were associated with good (12) or partial (7) response. Three complete remissions were observed. The median duration of response overall was 19.5 weeks, 26 weeks for the good and 10 weeks for the partial responders. A high incidence of treatment failure was seen in patients treated after transition to AML. Major complications were observed during 14 courses and mortality was directly related to therapy in five patients. Platelet transfusions were required during 26 courses. Aggravation of peripheral-blood cytopenia during the first weeks and hypocellularity of bone-marrow aspirates at the end of therapy suggest that low-dose Ara C exerts its main activity by suppression of leukaemic growth, rather than by induction of differentiation in malignant cells. Our results in MDS patients demonstrate that low-dose Ara C can be of value in severe cytopenia and can decrease the proportion of leukaemic cells in the bone marrow, but the danger of treatment should not be underestimated.     

Cytogenetic studies in 69 patients with myelodysplastic syndromes (MDS)

Cytogenetic studies were performed in 69 patients with myelodysplastic syndromes classified according to the FAB proposals. Overall incidence of chromosomal anomalies was 48% with 5q-, +8, 12p-,-7/7q- being the aberrations most often found. The 12p- chromosome showed a close correlation with a prior exposure to mutagenic agents and CMML. Although there were no group-specific cytogenetic anomalies, FAB classification strongly influenced their incidence. They were lower (36%) in RA/RA-S than in RAEB/RAEB-T/CMML (53%). Chromosomal anomalies were significantly more often found in patients with a prior exposure to carcinogenic agents (80%) than in unexposed patients (33%). The presence of chromosomal anomalies did not predict a higher risk of leukemic transformation.