Frequency of congenital dyserythropoietic anemias in Europe.

Congenital dyserythropoietic anemias (CDAs) are rare hereditary disorders characterized by ineffective erythropoiesis and striking abnormalities of erythroblast morphology. The mutated genes are known for the most frequent types, CDA I and II, but data about their frequency do not exist. The objective of this retrospective study was to estimate the frequency of CDA I and II, based on all cases reported in the last 42 yr in publications and identified registries or surveys. Reports were collected of 124 and 377 confirmed cases of CDA I and CDA II cases, respectively. The cumulated incidence of both types combined varied widely between European regions, with minimal values of 0.08 cases/million in Scandinavia and 2.60 cases/million in Italy. CDA II is more frequent than CDA I, with an overall ratio of approximately 3.2, but the ratio also varied between different regions. The most likely explanations for the differences are both differences in the availability of advanced diagnostic procedures and different levels of the awareness for the diagnosis of the CDAs. The estimations reported here are most probably below the true incidence rates, because of failure to make the correct diagnosis and to underreporting. Limited data do not suggest differing levels of risk in identified ethnic groups.

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia.

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.

Refractory anemia with ringed sideroblasts and thrombocytosis without JAK2 V617F mutation: report of three cases.

In the WHO classification, there is a provisional entity called Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/MPN, U). Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) was included in this category. Recently published studies report a small percentage of patients with RARS-T. Sixty percent of these have JAK2 V617F mutation, which can suggest the coexistence of two pathological conditions (MDS and MPN). In this paper, we analyzed three patients diagnosed with RARS-T in the Department of Hematology, "Fundeni" Clinical Institute, Bucharest, Romania, during the period 2005-2011. The patients were investigated with cytogenetic exam and molecular biology. In these three cases were identified morphological features of multilineage dysplasia (two-lineage dysplasia in two cases and three-lineage dysplasia in one case). In two cases, thrombocytosis was under 1000×10(3)/µL and clinical evolution was similar to the myelodysplastic syndrome (transfusion dependent anemia with response to administration of erythropoietin). In the third case, the platelets were over 1000×10(3)/µL and with response to the treatment with Hydrea, which improved anemia. JAK2 V617F mutation was not identified in any case. RARS-T remains a provisional entity and requires a complex investigation of patients for the correct diagnosis of these patients. Therapeutic options should be personalized to each case in part because there is not yet a standardized treatment of these patients.

Chronic myeloid leukemia--from the National to the European Registry--limited experience of a single center.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder in which the diagnosis is confirmed by detection of a genetic marker: Philadelphia (Ph) chromosome in almost 90% of cases. Some of Ph1 negative patients, nevertheless, test positive for the abnormal gene, or the abnormal protein associated with this chromosome, when more sensitive studies, such as PCR or FISH are used and nowadays the diagnosis of CML is based, not only on cytogenetic, but also on molecular analysis. The better understanding of the CML biology provided by the latest researches requires a deeper knowledge about the epidemiologic data in each geographic area, so the compiling of a National and/or European Registry for CML patients, that represents one of the aims of this study, became a stringent matter in our days; it can offer valuable data concerning the real incidence of this disease in Romania and can provide the basics for establishing long-term budgetary strategies.

Apoptotic rate in patients with myelodisplastic syndrome treated with modulatory compounds of pro-apoptotic cytokines.

Excessive apoptosis has a central role in ineffective hematopoiesis in myelodysplastic syndrome (MDS). The aim of the study was to quantify apoptosis and Bcl-2 expression in patients with MDS and to use these parameters in the evaluation of treatment efficacy with compounds modulating proapoptotic cytokines. Bone marrow (BM) samples from eight MDS patients were studied: four with refractory anemia and four with refractory anemia with ringed sideroblasts. Two patients with Hodgkin disease without BM determination were studied for control. Therapy consisted in administration of pentoxyphylline, dexamethasone and ciprofloxacin. Biochemical assay of apoptosis and Bcl-2 was performed using annexin V-biotin conjugate antibody and anti-human Bcl-2 antibody respectively, followed by streptavidine-peroxidase conjugate, and peroxidase substrate. Ultrastructural investigation of BM samples was performed with standard electron microscopy techniques. Most of BM hematopoietic cells in the MDS patients had ultrastructural features of various stages of apoptosis including chromatin condensation and margination, cytoplasm condensation and budding of nuclear and plasma membranes to produce apoptotic bodies. Bcl-2 expression showed an inverse correlation with the rate of the apoptotic process. Periodic evaluation of these two parameters has shown an increase of Bcl-2 expression and a decrease of apoptotic rate in patients who had responded to the treatment. Response to the treatment was appreciated in accordance with their transfusion needs. Treatment efficiency diminished in time. The rate of apoptosis was inversely correlated with the level of Bcl-2 expression. These results confirm the importance of the apoptotic process evaluation in monitoring MDS treatment.

Clinical and hematological aspects of chronic myelomonocytic leukemia. Study on 20 cases from a single center from Romania.

Chronic myelomonocytic leukemia (CMML) has long been recognized as a disorder with both myelodysplastic and myeloproliferative characteristics, some patients showing clinical and morphological features resembling myelodysplastic syndrome (MDS) especially refractory anemia with excess of blasts (RAEB) with monocytosis, and others leukocytosis with neutrophilia, monocytosis and splenomegaly resembling myeloproliferative syndrome (MPS). The intrinsec differences determined at first the separation of CMML in two forms, one named "dysplastic", more similar with RAEB, and the other "proliferative", closer to chronic myeloid leukemia and then included by the recent WHO classification into a separate new created group--myelodysplastic diseases (MDD)/chronic myeloproliferative diseases (CMPD). The aim of this study was the analysis of some features of 20 cases of CMML, with emphasis on the differences between the two forms. The proliferative form of CMML differed from the dysplastic one by greater white blood cells and neutrophils counts (P < 0.001), a more important monocytosis in periferal blood (P = 0.07), and by the size and frequency of splenomegaly (P = 0.03). The sex and age of the patients, the frequency of the general symptoms, the frequency of the general symptoms and signs and that of infections, the hemoglobin and hematocrit values, the platelet counts, the percentage of myeloblasts and monocytes in bone marrow, the frequency of dysplastic traits, the percentage of reticulocytes and the modified Bournemouth prognostic index were not significantly different. These findings support the concept that CMML is a heterogeneous "overlap" syndrome between MDS and CMPD.