MDS Patients (md + patient)

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Distribution within Medical Sciences


Selected Abstracts


Distinct sequences on 11q13.5 and 11q23,24 are frequently coamplified with MLL in complexly organized 11q amplicons in AML/MDS patients

GENES, CHROMOSOMES AND CANCER, Issue 4 2004
Andrea Zatkova
Amplification within chromosome arm 11q involving the mixed-lineage leukemia gene (MLL) locus is a rare but recurrent aberration in acute myeloid leukemia and myelodysplastic syndrome (AML/MDS). We and others have observed that 11q amplifications in most AML/MDS cases have not been restricted to the chromosomal region surrounding the MLL gene. Therefore, we implemented a strategy to characterize comprehensively 11q amplicons in a series of 13 AML/MDS patients with MLL amplification. Analysis of 4 of the 13 cases by restriction landmark genomic scanning in combination with virtual genome scan and by matrix-based comparative genomic hybridization demonstrated that the 11q amplicon in these four cases consisted of at least three discontinuous sequences derived from different regions of the long arm of chromosome 11. We defined a maximally 700-kb sequence around the MLL gene that was amplified in all cases. Apart from the core MLL amplicon, we detected two additional 11q regions that were coamplified. Using fluorescence in situ hybridization (FISH) analysis, we demonstrated that sequences in 11q13.5 and 11q23,24 were amplified in 8 of 13 and 10 of 12 AML/MDS cases, respectively. Both regions harbor a number of potentially oncogenic genes. In all 13 cases, either one or both of these regions were coamplified with the MLL amplicon. Thus, we demonstrated that 11q amplicons in AML/MDS patients display a complex organization and have provided evidence for coamplification of two additional regions on the long arm of chromosome 11 that may harbor candidate target genes. © 2004 Wiley-Liss, Inc. [source]


Major and minor depression in Parkinson's disease: a neuropsychological investigation

EUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2006
A. Costa
Previous studies have failed to distinguish the differential contribution of major and minor depression to cognitive impairment in patients with idiopathic Parkinson's disease (PD). This study was aimed at investigating the relationships among major depression (MD), minor depression (MiD) and neuropsychological deficits in PD. Eighty-three patients suffering from PD participated in the study. MD and MiD were diagnosed by means of a structured interview (SCID-I) based on the DSM-IV criteria, and severity of depression was evaluated by the Beck Depression Inventory. For the neuropsychological assessment, we used standardized scales that measure verbal and visual episodic memory, working memory, executive functions, abstract reasoning and visual-spatial and language abilities. MD patients performed worse than PD patients without depression on two long-term verbal episodic memory tasks, on an abstract reasoning task and on three measures of executive functioning. The MiD patients' performances on the same tests fell between those of the other two groups of PD patients but did not show significant differences. Our results indicate that MD in PD is associated with a qualitatively specific neuropsychological profile that may be related to an alteration of prefrontal and limbic cortical areas. Moreover, the same data suggest that in these patients MiD and MD may represent a gradual continuum associated with increasing cognitive deficits. [source]


Is muscle spindle proprioceptive function spared in muscular dystrophies?

MUSCLE AND NERVE, Issue 6 2004
A muscle tendon vibration study
Abstract Muscular dystrophies (MDs) are characterized by the degeneration of skeletal muscle fibers. The aim of the present study was to determine whether the intrafusal fibers of muscle spindles are also affected in MD. The functional integrity of muscle spindles was tested by analyzing their involvement in the perception of body segment movements and in the control of posture. Twenty MD patients (4 with dystrophinopathy, 5 with myotonic dystrophies, 5 with fascioscapulohumeral MD, and 6 with limb-girdle dystrophies) and 10 healthy subjects participated in the study. The MD patients perceived passive movements and experienced illusory movements similar to those perceived by healthy subjects in terms of their direction and velocity. Vibratory stimulation applied to the neck and ankle muscle tendons induced postural responses in MD patients with spatial and temporal characteristics similar to those produced by healthy subjects. These results suggest that the proprioceptive function of muscle spindles is spared in muscular dystrophies. Muscle Nerve 29: 861,866, 2004 [source]


Evaluation of Biventricular Functions With Tissue Doppler Imaging in Patients With Myotonic Dystrophy

CLINICAL CARDIOLOGY, Issue 3 2010
Tolga Ozyigit MD
Background: Myotonic dystrophy (MD) is characterized by myotonia with dystrophic involvement of the muscles. Cardiac involvement is usually not evident in the early stages of MD. Hypothesis: We investigated biventricular functions by tissue Doppler imaging (TDI) in MD patients with no overt cardiac involvement to explore the value of TDI in the early detection of myocardial dysfunction. Methods: A total of 21 MD patients (15 male, age: 32.2 ± 12.3 yrs) and 21 healthy controls (13 male, age: 32.2 ± 7.8 yrs) were included. In addition to conventional echocardiography, pulsed Doppler and TDI were performed including measurement of myocardial performance index (MPI); peak systolic (Sm) and early (Em) and atrial (Am) diastolic myocardial velocities at the basal mitral and tricuspid annulus. Results: All patients and controls had normal ejection fraction. Transmitral E peak velocity was significantly lower while both deceleration time of E velocity and isovolumic relaxation time were significantly longer in MD patients (P = 0.007, P = 0.001, and P < 0.001, respectively). Sm, Em and Am peak velocities were significantly lower in MD patients in all segments except for Em of the mitral anterior annulus and Am of the tricuspid lateral annulus. Both left and right ventricular MPI were significantly higher in MD patients (P < 0.001 and P = 0.013, respectively). Conclusion: There are changes in myocardial systolic and diastolic functions in MD patients although they have no overt heart failure. Myocardial tissue velocities and MPI are useful in identifying subclinical biventricular involvement in these patients. Copyright © 2010 Wiley Periodicals, Inc. [source]


Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome: a marker of karyotypic abnormalities associated with poor prognosis

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009
Naomi Sugimori
Abstract Objectives:, Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 51 patients recently diagnosed with MDS. Method:, Subjects consisted of 80 healthy males, 90 healthy females, and 51 patients with MDS and 20 patients with idiopathic thrombocytopenic purpura (ITP). The IPF and IPF% were determined using a Sysmex XE-2100 system loaded with IPF Master software (XE IPF Master, Sysmex). Platelet counts were measured simultaneously. Results:, IPF% and platelet counts of these patients ranged from 1.1% to 25.1% (median, 5.3%) and from 6 to 260 × 109/L (median, 71 × 109/L), respectively. Twelve patients showed platelet counts more than 50 × 109/L with 10% or more IPF%. All of the 12 patients had chromosome abnormalities including monosomy 7 and complex abnormalities involving 7 or 5q. In the other 39 patients who did not show the aberrant IPF% increase, chromosomal abnormalities were seen only in seven patients and none of them had chromosome 7 abnormalities. The IPF% of two patients increased to more than 10% in association with the appearance of monosomy 7. Conclusions:, These findings suggest that a high IPF% in MDS patient may be a marker for karyotypic abnormalities with a poor prognosis, including chromosome 7 abnormalities. [source]


Abnormal WT1 expression in the CD34-negative compartment in myelodysplastic bone marrow

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2002
Jeroen P. Van Dijk
Summary. In normal bone marrow, WT1 expression is restricted to CD34+ cells. We assessed WT1 mRNA expression levels with quantitative, real-time reverse transcription polymerase chain reaction in normal, myelodysplastic (MDS) and secondary acute myeloid leukaemia (sAML) bone marrow subfractions, based on differentiation status. The highest WT1 expression was observed in the primitive CD34+ rhodamine-123 (rho) dull cells, both in healthy donors and MDS or sAML patients. In contrast to normal CD34-negative bone marrow cells, WT1 was present in CD34-negative bone marrow cells in 12 out of 13 MDS patients and two sAML samples. Further analysis of this aberrant WT1 expression was performed in the CD34-negative subfractions of three MDS patients. In one of these, WT1 expression was found exclusively in the erythroid cells. This patient was completely transfusion dependent and showed morphological dyserythropoiesis. In another MDS patient, WT1 expression was found in a non-erythroid compartment. We conclude that abnormal WT1 expression may contribute to the disturbed differentiation of haematopoietic cells in MDS patients. [source]


Quantitative, phenotypic, and functional evaluation of basophils in myelodysplastic syndromes

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2001
W. Füreder
Background The myelodysplastic syndromes (MDS) are a group of clonal haematological disorders characterized by cytopenia(s), reduced differentiation-capacity of myeloid cells, and impaired leukocyte function. However, little is known so far about basophil granulocytes in MDS. Design We have compared the numbers, phenotype and function of basophils in MDS patients with those in healthy subjects. A total numer of 23 patients with MDS (refractory anaemia, n = 8; refractory anaemia with ringsideroblasts, n = 7; refractory anaemia with excess of blasts/refractory anaemia with excess of blasts in transformation, n = 8) and 20 healthy donors were included. Results The numbers of blood basophils in MDS patients (34·6 ± 62·9 ,L,1) was lower compared to healthy controls (58·6 ± 64·9 ,L,1). Correspondingly, whole blood histamine levels were lower in MDS patients (MDS 34·1 ± 29·1 ng mL,1 vs. normal donors 72·0 ± 36·9 ng mL,1). Like ,normal' basophils, basophils in MDS expressed interleukin-3 receptor , (CD123), E-NPP3 (CD203c), CR1 (CD35), CR3 (CD11b), CR4 (CD11c), membrane co-factor protein (CD46), decay-accelerating factor (CD55) and membrane attack complex inhibitory factor (CD59), as well as receptors for C3a, C5a (CD88), and IgE. Recombinant human (rh) C5a and anti-IgE induced significant release of histamine from basophils in both groups of donors without significant differences between MDS and healthy controls. Conclusions The absolute numbers of basophils in MDS patients are lower than in normal donors. However, basophils in MDS do not differ from their ,normal counterparts' in terms of complement receptor expression, IgE-receptor expression, or functional responses to respective ligands. [source]


Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007
Hussam Ghoti
Abstract Low-risk myelodysplastic syndrome (MDS) is characterized by cytopenia, mainly anemia, because of ineffective hematopoiesis. Some of the patients with ineffective erythropoiesis, with or without ring sideroblasts in their bone marrow, develop severe anemia requiring frequent blood transfusions and consequently develop iron overload. Excess free iron in cells catalyses the generation of reactive oxygen species (ROS) that cause cell and tissue damage. Using flow cytometry techniques, we compared the oxidative status of red blood cells (RBC), platelets and neutrophils in 14 MDS patients with those of normal donors. The results show that ROS were higher while reduced glutathione (GSH) was lower in their RBC and platelets compared with normal cells. In neutrophils, no difference was found in ROS, while the GSH levels were lower. A correlation (r = 0.6) was found between serum ferritin levels of the patients and the ROS in their RBC and platelets. The oxidative stress was ameliorated by a short incubation with the iron-chelators, the deferrioxamine and deferiprone or with antioxidants such as N -acetylcysteine, suggesting that MDS patients might benefit from treatment with iron-chelators and antioxidants. [source]


The soluble transferrin receptor in dysplastic erythropoiesis in myelodysplastic syndrome

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007
Georgia Metzgeroth
Abstract Objectives:,In individuals without iron deficiency, the soluble transferrin receptor (sTfR) directly reflects the erythropoietic activity. This study investigated sTfR concentrations in ineffective, dysplastic erythropoiesis in myelodysplastic syndrome (MDS). Methods:,To exclude influences of other myeloid cells on sTfR, only patients with refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS) and 5q, syndrome were included. sTfR was measured nephelometrically (normal range 0.81,1.75 mg/L). Results:,Thirty-four untreated MDS patients (RA = 14, RARS = 10, 5q, syndrome = 10) were enrolled and analysed. The mean sTfR value of all MDS patients (1.30 ± 0.8 mg/L, range 0.2,3.8) did not differ from our control group. In 5q, syndrome, the mean sTfR concentration (0.80 ± 0.5 mg/L) was significantly lower than in RA (1.32 ± 0.4 mg/L, P = 0.02) and RARS (1.75 ± 1.1 mg/L, P = 0.03). Subdividing MDS according to their amount of erythroid mass in bone marrow a significant difference of sTfR between patients with decreased (0.70 ± 0.4 mg/L), normal (1.32 ± 0.4 mg/L) and increased (2.06 ± 0.9 mg/L) erythropoiesis was observed. MDS patients with sTfR values below the reference range of 0.81 mg/L required transfusions in 90% of cases and showed higher erythropoietin levels compared to MDS patients with sTfR levels ,0.81 mg/L (P = 0.01). There was a good agreement between sTfR and the amount of polychromatic erythroblasts observed (r = 0.68, P < 0.001). Conclusion:,In conclusion, the serum concentration of sTfR reflects erythropoietic activity in MDS, but it is in particular determined by the degree of erythroid maturation and the severity of ineffective erythropoiesis. Low sTfR values in MDS are associated with a reduced, poorly differentiated erythropoiesis and requirement of blood transfusions. [source]


Matrix metalloproteinase inhibitor reduces apoptosis induction of bone marrow cells in MDS-RA

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2004
Kosei Arimura
Abstract:,Background and objectives:,We examined the involvement of apoptosis with myelodysplastic syndrome (MDS) accompanied by peripheral cytopenias despite normo-hypercellular bone marrow. Materials and methods:,Bone marrow smears from 31 patients with MDS-refractory anemia (RA) and five normal controls were stained using the in situ end labeling (ISEL) method. Next, the inhibitory effects of a caspase-3 inhibitor, matrix metalloproteinase inhibitor (MMPI), anti-tumor necrosis factor (TNF)- , or anti-Fas antibody upon the apoptosis induction in overnight cultures of bone marrow cells from the patients were examined. Further, TNF- ,, transforming growth factor (TGF)- , and soluble Fas ligand (sFasL) concentrations in culture supernatants of the cells were assessed by enzyme-linked immunosorbent assay (ELISA). Results:,The incidence of ISEL-positive cells among MDS patients was significantly higher than in normal controls (50.8 ± 14.0% vs. 11.3 ± 2.4%; P < 0.0001). A caspase-3 inhibitor reduced significantly the ISEL-positive rates (32.6 ± 15.2% vs. 50.2 ± 16.5%; P < 0.0001). Anti-TNF- , or anti-Fas antibody reduced the ISEL-positive rates significantly (28.2 ± 6.0%, 29.2 ± 5.8%, vs. 44.2 ± 3.4%, P < 0.001, P = 0.001, respectively). KB-R7785 also significantly decreased the ISEL-positive rates (18.0 ± 9.3% vs. 43.6 ± 14.0%; P < 0.0001). The concentration of TNF- , was significantly reduced by KB-R7785 (P < 0.05), whereas that of TGF- , was not. Concentration of sFasL was under detectable level in the present assay system. The derivatives of KB-R7785 that can be administrated orally showed inhibitory effect on apoptosis induction as well. Conclusions:,These findings suggest that MMPIs inhibits the apoptosis induction of MDS bone marrow cells via the inhibition of TNF- , and probably sFasL secretion, and that MMPIs can be used to control the abnormal induction of apoptosis in MDS. [source]


The utility of the Sysmex XE-2100 analyzer's NEUT-X and NEUT-Y parameters for detecting neutrophil dysplasia in myelodysplastic syndromes

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2010
J. R. FURUNDARENA
Summary The diagnosis of myelodysplastic syndromes (MDS) is based on morphological changes in the blood and bone marrow. The parameters NEUT-X and NEUT-Y of the Sysmex XE-2100 analyzer could help detect neutrophil dysplasia. A control group of 50 patients, along with 50 postpartum patients, 50 anemias, 50 leukopenias, 50 patients with microscopically visible hypergranulated neutrophils and 50 MDS patients were assessed. The NEUT-X and NEUT-Y values (mean ± SD) for the control group were 1346 ± 28.2 and 420 ± 19.3, respectively, with the anemia and leukopenia groups giving similar values. The postpartum and hypergranulated neutrophils groups presented higher values (P < 0.05), whereas the values in the MDS group were 1286 ± 72.8 and 385 ± 50.9 (P < 0.05), respectively. There were no differences between the morphological MDS types. The NEUT-X and NEUT-Y values in MDS patients with optical hypogranulation were significantly lower than for MDS patients without optical hypogranulation. NEUT-X and NEUT-Y values lower than 1298 and 398, respectively, would have a specificity for detecting MDS of 94% and 91% and would detect 60% and 56% of cases, respectively, whereas they would detect 75% and 74%, respectively, of MDS cases with optical hypogranulation. NEUT-X and NEUT-Y parameters can be used to detect neutrophil dysplasia arising from MDS and chronic myelomonocytic leukemia. [source]


Myeloablative hematopoietic stem cell transplantation for myelodysplastic syndrome in patients younger than 55 years: impact of comorbidity and disease burden on the long-term outcome

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010
H. KANAMORI
Summary We retrospectively investigated 31 myelodysplastic syndrome (MDS) patients receiving myeloablative hematopoietic stem cell transplantation (HCT) and focused on prognostic factors affecting the long-term outcome. Patients were classified according to the French-American-British classification and the HCT-comorbidity index was determined. Cytosine arabinoside or thiotepa combined with cyclophosphamide and total body irradiation was used as myeloablative conditioning in eight and 23 patients respectively. After a follow-up period of 0.8,14.2 years from transplantation (median: 6.4 years), 23 patients were alive in complete remission, and the 5-year overall survival (OS) and disease-free survival (DFS) rates were 79% and 72% respectively. The cumulative nonrelapse mortality (NRM) rate was 22% at 5 years. According to multivariate analysis, ,20% blasts in the bone marrow and an HCT-comorbidity score , 3 were significantly associated with poor OS and DFS. Patients with a high HCT-comorbidity score and male patients receiving transplantation from female donors were significantly more likely to have a higher NRM according to the univariate, but not the multivariate analysis. These data suggest that comorbidity and the tumor burden at the time of transplantation may be useful variables for predicting the outcome in MDS patients receiving myeloablative HCT. [source]


Comparative analysis of G-CSFR and GM-CSFR expressions on CD34+ cells in patients with aplastic anemia and myelodysplastic syndrome

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2009
H. XU
Summary The aim of this article was to explore the pathogenetic differences, as well as to provide a new way for the differential diagnosis of these two diseases by comparative analysis of CD34+ cells numbers and their surface expression of granulocyte colony-stimulating factor receptor (G-CSFR) and granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). Twenty-seven patients with AA, 45 patients with MDS, and 20 normal controls were enrolled in this study. The ratio of CD34+ cells and their surface expression of G-CSFR and GM-CSFR were detected by flow cytometry (FCM). The ratio of CD34+ cells in BMMNC of AA, MDS patients and controls were 0.2438 ± 0.1129%, 2.1677 ± 1.1345% and 1.0792 ± 0.3221%, respectively. Compared with normal controls as well as MDS patients, the ratio of CD34+ cells in BMMNC of AA was significantly reduced (P < 0.05). The ratio of CD34+ cells in MDS was significantly elevated than controls (P < 0.05). The ratio of CD34+ cells in BMMNC of MDS-RA and MDS-RAEB patients were 1.2821 ± 0.4658% and 3.7729 ± 2.3360%, respectively. Compared with normal controls and MDS-RA patients, the ratio of CD34+ cells in MDS-RAEB was significantly elevated (P < 0.05). The ratio of CD34+ cells in MDS-RA was significantly elevated than AA patients (P < 0.05). The surface expression of G-CSFR on CD34+ cells of AA, MDS patients and controls were 34.402 ± 21.8357%, 26.376 ± 15.2895% and 21.443 ± 7.4465%, respectively. The surface expression of G-CSFR on CD34+ cells of MDS-RA and MDS-RAEB patients were 22.788 ± 14.7628% and 30.682 ± 15.5346%. The surface expression of GM-CSFR on CD34+ cells of AA, MDS patients and controls were 6.5961 ± 4.4322%, 18.2737 ± 10.9841% and 4.2753 ± 2.6249%, respectively. Compared with AA and controls, the expression of GM-CSFR in MDS patients was significantly elevated (P < 0.05). The surface expression of GM-CSFR on CD34+ cells of MDS-RA and MDS-RAEB patients were 16.1625 ± 6.9487% and 22.1003 ± 14.2983%. In AA patients, the ratio of CD34+ cells in BMMNC less than 0.1% accounts for 75% (6/8) SAA patients, compared with 10.55% (2/19) in CAA (P < 0.05). The detection of CD34+ cells and their surface expression of granulocyte (macrophage) colony-stimulating factor receptors G (M)-CSFR in AA and MDS are helpful in the differential diagnosis or prognosis of these two disorders. [source]


Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2001
C.H. Hui
Management options are often limited for patients with AML or high grade myelodysplasia (MDS) relapsing within a year of allogeneic transplantation. We report, in two such patients, the use of re-induction with FLAG-Ida chemotherapy, followed by the infusion of GCSF-mobilized blood stem cells from the same HLA-matched donor. Both patients achieved durable complete remissions with good quality of life and longer disease-free survival than after the first myeloablative allografts. This mini-allograft approach offers a practical, well-tolerated salvage and a potentially curative treatment for relapsed AML/high grade MDS patients failing a first conventional myeloablative allogeneic transplants. [source]


Incidence of myelodysplastic syndromes within a nonprofit healthcare system in western Washington state, 2005,2006,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010
Anneclaire J. De Roos
Myelodysplastic syndromes (MDS) incidence is unclear because of historical lack of population-based registration and possibly because of underdiagnosis. We conducted a study to evaluate completeness of MDS registration in the Seattle-Puget Sound region of the Surveillance, Epidemiology, and End Results (SEER) program,which has reported the highest rates among the SEER registries since mandatory reporting of MDS began in 2001. We identified incident MDS cases of any age that occurred within a nonprofit healthcare system in western Washington State in 2005 or 2006 through the local SEER registry or by relevant diagnostic code followed by medical chart review to classify these patients as unlikely, possible, or definite/probable MDS. We calculated age-standardized incidence rates for all identified MDS cases and for case groups based on identification method, and we summarized medical histories of the MDS patients. MDS incidence in our study population was estimated as 7.0 per 100,000 person-years in 2005,2006 when combining MDS cases identified by SEER and definite/probable cases identified by chart review, which was similar to the rate of 6.9 reported by our local SEER registry. The addition of possible MDS cases identified from chart review increased the rate to 10.2 per 100,000. MDS patients frequently had previous cancer diagnoses (25%) and comorbidities such as high blood pressure and diabetes. Our investigation suggests that although reporting of confirmed MDS diagnoses in our region appears complete, MDS incidence is likely underestimated because of omission of cases who are symptomatic but do not receive definitive diagnoses. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]


A Phase II intra-patient dose-escalation trial of weight-based darbepoetin alfa with or without granulocyte-colony stimulating factor in myelodysplastic syndromes,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2009
Jason Gotlib
This Phase II study evaluated darbepoetin alfa (DA) in 24 patients with predominantly low or intermediate-1 risk myelodysplastic syndrome (MDS). Intra-patient dose escalation of DA was undertaken in three 6-week dose cohorts until a major erythroid response was achieved: 4.5 mcg/kg/week, 9 mcg/kg/week, and 9 mcg/kg/week plus granulocyte-colony stimulating factor (G-CSF) 2.5 mcg/kg twice weekly. Patients with refractory anemia with ringed sideroblasts (RARS) commenced DA at 9 mcg/kg/week. The weight-based dosing regimen translated into a median starting DA dose of 390 mcg/week. Erythroid responses were observed in 16/24 patients (67%; 12 major and 4 minor), with a median response duration of 11 months in major responders. Addition of G-CSF generated a major erythroid response in 7/15 patients (47%) who suboptimally responded to DA alone. DA was well tolerated, except for worsening of baseline mild hypertension and renal insufficiency in one patient with diabetes. IPSS score <0.5 and RBC transfusions <2 units/month increased the probability of an erythroid response. A minority of subjects (12%) developed low-level non-neutralizing anti-DA antibodies. Our data indicate that weekly weight-based dosing of DA, with the addition of G-CSF in selected individuals, can be an effective erythropoietic option in a high proportion of lower-risk MDS patients. Am. J. Hematol, 2009. © 2008 Wiley-Liss, Inc. [source]


In patients with myelodysplastic syndromes response to rHuEPO and G-CSF treatment is related to an increase of cytogenetically normal CD34+ cells

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004
Gian Matteo Rigolin
Summary The in vivo effect of recombinant human erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) combined treatment on CD34+ cells was evaluated by fluorescence in situ hybridization (FISH) in 13 myelodysplastic syndrome (MDS) patients with known cytogenetic abnormalities. After treatment, responsive patients presented a significantly lower proportion of FISH abnormal CD34+ cells than before treatment (P = 0·003), and in comparison with unresponsive cases (P = 0·007). Response to treatment was associated with a reduced degree of apoptosis in CD34+ cells (P = 0·021): however, no difference in telomere length was observed in responsive patients after growth factor administration. Although the number of patients analysed was relatively small, the present data suggest that, in MDS patients, response to rHuEpo and G-CSF may be related to the proliferation of karyotypically normal but potentially defective CD34+ progenitor cells. [source]


Abnormal WT1 expression in the CD34-negative compartment in myelodysplastic bone marrow

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2002
Jeroen P. Van Dijk
Summary. In normal bone marrow, WT1 expression is restricted to CD34+ cells. We assessed WT1 mRNA expression levels with quantitative, real-time reverse transcription polymerase chain reaction in normal, myelodysplastic (MDS) and secondary acute myeloid leukaemia (sAML) bone marrow subfractions, based on differentiation status. The highest WT1 expression was observed in the primitive CD34+ rhodamine-123 (rho) dull cells, both in healthy donors and MDS or sAML patients. In contrast to normal CD34-negative bone marrow cells, WT1 was present in CD34-negative bone marrow cells in 12 out of 13 MDS patients and two sAML samples. Further analysis of this aberrant WT1 expression was performed in the CD34-negative subfractions of three MDS patients. In one of these, WT1 expression was found exclusively in the erythroid cells. This patient was completely transfusion dependent and showed morphological dyserythropoiesis. In another MDS patient, WT1 expression was found in a non-erythroid compartment. We conclude that abnormal WT1 expression may contribute to the disturbed differentiation of haematopoietic cells in MDS patients. [source]


Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia

CANCER, Issue 9 2002
In vitro, in vivo studies
Abstract BACKGROUND Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure. METHODS Using flow cytometry, we studied Fas-receptor (Fas-R), Fas-ligand (Fas-L), and interferon-, (IFN-,) expression in CD34+ cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long-term cultures, the effects of Fas triggering, IFN-, blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony-forming cells [CFC]) were determined. The effects of CsA at daily doses of 1,3 mg/kg for at least 3 months in HMDS patients were also studied. RESULTS In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN-,,expressing CD4+ cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas-L expression was only borderline elevated in CD3+ MDS cells. Increased numbers of CD34+ cells expressing Fas-R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas-L,mediated inhibition and the blockade of IFN-, improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN-,,expressing CD4+ cells, but not Fas-L production. These effects were associated with increased colony formation. Similar to IFN-,blockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients. CONCLUSIONS Increased frequency of IFN-, producing CD4+ cells supports the involvement of lymphocyte-mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN-, production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients. Cancer 2002;95:1911,22. © 2002 American Cancer Society. DOI 10.1002/cncr.10915 [source]


Redefining monosomy 5 by molecular cytogenetics in 23 patients with MDS/AML

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007
Angèle Herry
Abstract Deletion of the long arm of chromosome 5 [del(5q)] or loss of a whole chromosome 5 (,5) is a common finding, arising de novo in 10% of patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and in 40% of patients with therapy-related MDS or AML. We investigated by molecular cytogenetics 23 MDS/AML patients for whom conventional cytogenetics detected a monosomy 5. Monosomy 5 was redefined as unbalanced or balanced translocation and ring of chromosome 5. Loss of 5q material was identified in all 23 patients, but one. One copy of EGR1(5q31) or CSF1R(5q33,34) genes was lost in 22 of the 23 patients. Chromosome 5p material was a constant chromosomal component of derivative chromosomes or rings in all patients, but one. Sequential fluorescent in situ hybridization studies with whole chromosome paints and region-specific probes, used as a complement to conventional cytogenetic analysis, allow a better interpretation of karyotypes in MDS/AML patients. [source]