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PubMed1998

Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with ANLL or MDS and abnormalities of the short arm of chromosome 12.

Abnormalities of the short arm of chromosome 12 (12p) are found in about 5% of acute nonlymphocytic leukaemias (ANLL) and myelodysplastic syndromes (MDS). They are described to be characteristic of secondary leukaemias, especially after prior mutagenic exposure, and to be associated with a poor prognosis. In our series of 59 patients with 12p abnormalities and ANLL or MDS, exposure to genotoxic agents was proven only in five patients, but in 13/44 patients ANLL evolved from an MDS. Patients with a small deletion del(12)(p11.2p13) having a mild clinical course were distinguished from those with a large del(12)(p11.2), additional chromosomal anomalies, and a poor clinical course. Among the 31 patients with translocations or dicentric chromosomes involving 12p, a group of eight with t/dic(12;13) was the most frequent and was associated with a poor prognosis. The clinical outcome was adverse in the majority of patients with complex karyotype abnormalities, but in some patients a milder clinical course seems likely. A new, hitherto undescribed, abnormality in an MDS case with a duplication dup(12)(p11.2p13) was the amplification of the signal of the yeast artificial chromosome (YAC) clone 964c10 (D12S736). In 38 cases with deletions or unbalanced translocations/dicentrics one YAC signal was lost. Five patients with balanced translocations demonstrated breakpoints within the YAC, containing the ETV6 (TEL) gene. The breakpoints were telomeric to the YAC 964c10 in seven cases and centromeric in one patient.

Adult↗
PubMed1999

Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology. Scandinavian MDS Group, Sweden and Norway.

Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.

Aged↗
PubMedDate not supplied

[Relapse of childhood ALL, AML and MDS after allogeneic stem cell transplantation can be prevented by donor lymphocyte infusion in a critical stage of increasing mixed chimerism].

BACKGROUND: Mortality in children with acute leukemias or MDS after allogeneic stem cell transplantation (allo-SCT) is mostly determined by relapses. It was recently shown by us that patients who develop increasing quantities of autologous hematopoietic cells in peripheral blood (increasing mixed chimerism, in-MC) after allo-SCT do significantly more often relapse (P < 0.0001) than patients with a complete chimerism (CC). In a small series of patients with in-MC, the relapse rate could be significantly reduced by administration of donor lymphocytes (DLI). METHODOLOGY: A prospective multicenter study was initiated under the question whether number of relapses can be significantly reduced either by withdrawal of post-transplant immunosuppression and/or by DLI in the critical stage of in-MC. RESULTS: Highly repetitive determination of the genetic status of 114 children with acute leukemias or MDS (ALL: n = 41, AML: n = 39, MDS: n = 34) revealed 55 cases with CC and 43 with in-MC. Relapses occurred significantly (P < 0.0001) more often in patients with in-MC (25/43) than in patients with CC (12/55). In-MC-patients showed a significantly (P < 0.01) enhanced event free survival rate (11/24) when DLI was given and/or post-transplant immunosuppression was stopped compared to patients which did not receive such an interventional regimen (1/19). Two in-MC-patients developed fatal GVHD after immunological intervention. CONCLUSION: These data substantiate that prophylactic immunotherapy on the basis of in-MC is a powerful treatment approach to suppress relapses of acute leukemias and MDS after allo-SCT.

Cause of Death↗
PubMed1990

Functional studies of bone marrow haemopoietic and stromal cells in the myelodysplastic syndrome (MDS).

Long-term bone marrow culture (LTBMC) was used to investigate the proliferative behaviour of marrow cells from a spectrum of cases of the myelodysplastic syndrome (MDS), and the results compared with those obtained in the conventional short-term clonal assay. Two broad patterns of growth were revealed in LTBMC. In one group the incidence of haemopoietic progenitor cells steadily declined to abnormally low levels at 4 weeks, while in a second group they were maintained near normal levels for periods of up to 7 weeks. These growth patterns, which were not predictable from clonogenic assays on the marrow cells prior to LTBMC, or from the morphology of the bone marrow, may reflect the stage of evolution of the disease. Further studies of clonality are required to establish whether or not patients exhibiting the second pattern have a potentiality to harbour residual normal haemopoiesis. LTBMC was also used to study the function of MDS marrow stroma in terms of its ability to sustain the growth of normal haemopoietic progenitor cells. Although the phenotype of the cultured adherent cell layer, obtained from some patients, was atypical, no consistent functional defect of MDS stroma could be identified by studying the level of haemopoiesis reached by normal cells seeded into MDS stroma.

Adolescent↗
PubMed1992

Clonal lymphocytes are detectable in only some cases of MDS.

Clonal analysis of lymphocytes from patients with myelodysplastic syndrome (MDS) has been carried out using X-chromosome inactivation patterns detected by the probe M27 beta, and by polymerase chain reaction amplification of the immunoglobulin heavy chain gene hypervariable region, CDR3. Of 32 female patients heterozygous for M27 beta only seven (22%) demonstrate monoclonality of peripheral blood lymphocytes. 12 (37%) give unequivocal polyclonal results and the remaining cases give patterns of X-inactivation which cannot be interpreted either way. A study of 68 MDS patients showed five (7%) with a population of B-cells with a monoclonal rearrangement of CDR3 compared with none out of 60 normal individuals, none out of 15 with B-non Hodgkin lymphoma (B-NHL) in remission and 19 out of 25 (75%) of cases of B-chronic lymphocytic leukaemia (B-CLL). Monoclonal lymphocytes were found by both techniques in only two females with MDS. We conclude that the presence of polyclonal lymphocytes is a common finding in patients with MDS.

Adult↗
PubMed1993

Familial MDS with 5q- abnormality.

Abnormalities of chromosome 5 and 7 are frequently found in primary MDS. Cases with familial monosomy 7 are well recognized, but there are no reports of familial MDS with deletion of 5q. We describe two sisters, aged 38 and 36 years, both of whom had MDS and interstitial deletion of 5q. The occurrence of this chromosomal abnormality reinforces the concept of tumour suppressor gene hypothesis in some cases with familial MDS.

Adult↗
PubMed1990

Comparative study of immunocytochemical staining versus Giemsa stain for detecting dysmegakaryopoiesis in myelodysplastic syndromes (MDS)

23 patients with myelodysplastic syndromes (MDS) and 8 normal controls were analyzed for dysmegakaryopoiesis (DMP) in the bone marrow by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique and by conventional May-Giemsa staining. In the immunocytochemical study, monoclonal antibody (MoAb) against glycoprotein (GP) IIb/IIIa was utilized to demonstrate megakaryocytic cells. 91% (21/23) of MDS cases were detected as having DMP by APAAP method, while only 52% (12/23) were detectable by Giemsa stain. There were difficulties in recognizing small micromegakaryocytes (micro MKs), designated as type 1 atypical MKs, by Giemsa staining. Furthermore, megakaryoblasts (MKBs) were detectable only by APAAP technique. In 8 normal controls, no type 1 and type 3 atypical MKs (round shaped multinuclear MKs) were observed either by Giemsa staining or by the APAAP method, suggesting that they are a distinctive feature of MDS. These results indicate the necessity of immunocytochemical technique for accurate recognition of DMP in MDS.

Anemia↗
PubMedDate not supplied

Nursing directors' perceptions of the dental components of the Minimum Data Set (MDS) in nursing homes.

The Directors of Nursing (DON's) of all 428 nursing homes in the state of Iowa were sent a pre-tested questionnaire. The aim of the study was to examine the perceptions by nursing directors on the utility of a dental component of the Minimum Data Set (MDS) in identifying residents with dental problems in their facility. The return rate was 55.1% from the DON's. It was reported that 66.4% of the homes had a training program for the MDS and that in 38.0% of the homes there was only one person doing the assessments. The majority (76.0%) of the DON's stated that the MDS was useful in tracking residents and that it did help them to identify dental problems. When asked how often it was useful in the identification of dental needs, only 9% stated that it was often useful. Also, regarding frequency of dental appointments for the residents, a mean of 51.0% of residents were estimated to have received some dental care during the previous year (means of 33.2% at the facility, 22.4% at a dental office, and 0.4% in a hospital). If change is to occur, the dental profession must try to get the nursing home assessors to convince the nursing homes to use the oral/nutritional/dental sections of the MDS as they were intended under the OBRA regulations.

Appointments and Schedules↗
PubMed1991

Dysmegakaryopoiesis in myelodysplastic syndromes (MDS): an immunomorphometric study of bone marrow trephine biopsy specimens.

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens of the bone marrow in 40 patients (23 men and 17 women, mean age 62 years) with different subtypes of myelodysplastic syndromes (MDS) to determine dysmegakaryopoiesis, but particularly precursor cells--that is, pro- and megakaryoblasts. In 31 of the 40 patients the numbers of megakaryocytes were increased which was associated with a predominance of smaller cell forms (micromegakaryocytes). Compared with periodic acid Schiff, immunostaining with a formalin resistant monoclonal antibody against glycoprotein IIIa (Y2/51(CD61) showed a clinically important proportion of immature elements. These could be designated pro- and megakaryoblasts by taking morphometric measurements on smears and bone marrow sections. There was a relevant increase in the number of promegakaryoblasts in 32 patients, consistent with uncontrolled expansion of the precursor pool. Seventeen repeated bone marrow biopsy specimens taken after chemotherapy largely showed a decrease in the numbers of megakaryocytes including the precursor cell population. Moreover, morphometric evaluation disclosed that micromegakaryocytes in MDS differ significantly from those in chronic myeloid leukaemia (CML) due to distinctive nuclear features and a disturbed nuclear:cytoplasmic ratio. These changes generate a more pleomorphic or atypical appearance of this cell population in MDS, compared with micromegakaryocytes in CML. It is concluded that the disproportionate increase in megakaryocyte precursors and the grossly abnormal aspects of micromegakaryocytes in MDS are characteristics of the severe defect involving haematopoiesis in this disorder.

Adult↗
PubMed2003

Contribution of beta-2 microglobulin levels to the prognostic stratification of survival in patients with myelodysplastic syndrome (MDS).

Prospective analysis of the importance of the plasma levels of beta-2 microglobulin (B2M) in 553 patients with myelodysplastic syndrome (MDS) found that B2M is an independent prognostic variable for survival with weighted significance second only to the karyotype. The incorporation of the B2M covariate into risk assessment of MDS patients added significantly to the power of the IPSS to stratify MDS patients into risk categories. Our results further document that the 2 objectively measured covariates that display the highest power to predict survival, that is, karyotype and B2M, can alone be used for risk stratification. While the results must be verified in an independent and comparable population, our data strongly recommend routine measurement of B2M in patients with MDS.

Female↗
PubMed2000

Acute myeloblastic leukemia secondary to myelodysplasia (MDS-AML): a comparison of remission induction with three drugs versus standard two-drugs induction.

To evaluate the addition of a third drug to standard induction chemotherapy in patients with MDS-AML, 23 patients (males/females 13/10, median age 54.3 years, range 24-74 years, median MDS duration 9.8 months, range 2-39 months) who received a standard 2-drugs induction were compared with 23 patients (males/females 11/12, median age 45.6 months, range 21-60 years, median MDS duration 8.3 months, range 2-29 months) who received an intensified 3-drugs induction with etoposide. CR rate, median CR duration and median OS were similar in both groups (48% vs 56%, 4.8 vs 5.9 months, 6.5 vs 7.0 months respectively). Among responding patients, all but one, who underwent allogeneic bone marrow transplantation, relapsed. In conclusion, addition of a third drug (etoposide) does not seem to significantly improve the poor prognosis of MDS-AML patients.

Adult↗
PubMed1999

[Evaluation and improvement of medical and nursing service and caregiving for the elderly using MDS. 1. Diagnosis and some problems in dementias].

A Minimum Data Set (MDS) was recorded in two geriatric hospitals every 4 months for about 5 years. The initial records were available in a total of 1,735 disabled elderly. In MDS, about 360 trigger items were recorded. A selection was made to determine whether there were problems of care in 18 areas of Resident Assessment Protocols. We analyzed errors and biases in selection of the diagnosis in the chapter E of MDS disclosing that: 1) they were almost satisfactorily made in diseases except dementias, 2) diagnosis of dementias was biased in several ways, particularly Alzheimer's disease was overselected, and 3) preprinted diagnostic options in MDS were not suited with the Japanese practice and were insufficient for comprehensive medical/nursing service and caregiving.

Aged↗
PubMed2006

[Epidemiology of visceral mycoses in patients with leukemia and MDS - Analysis of the data in annual of pathological autopsy cases in Japan in 1989, 1993, 1997 and 2001].

To study the changes of visceral mycoses in autopsy cases, data on visceral mycosis cases with leukemia and myelodysplastic syndrome (MDS) reported in the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993, 1997 and 2001 were analyzed. The frequency rate of visceral mycoses with leukemia and MDS was 27.9% (435/1,557) in 1989, 23.0% (319/1,388) in 1993, 22.3% (246/1,105) in 1997 and 25.1% (260/ 1,037) in 2001, which was clearly higher than the rate of cases without leukemia and MDS: 3.4%, 2.7%, 3.5% and 3.7%, respectively. Furthermore, in comparing the rate of mycoses in recipients of stem cell transplantation with that of non-recipients, that of recipients was about 10% higher. The predominant causative agents were Candida and Aspergillus, at approximately the same rate (Candida 33.6%, Aspergillus 33.3%) as in 1989. However, Aspergillus increased conspicuously in 1993 (Candida 22.3% Aspergillus 44.5%), and continued to increase (Candida 22.8%, Aspergillus 50.8% in 1997; Candida 16.9%, Aspergillus 54.2% in 2001). In aspergillosis and zygomycosis, the lung and bronchi comprised the most commonly infected organs: 74.7% and 75.6% of the total cases, respectively. Among a total of 1,260 cases with mycotic infections in the four years studied, acute lymphatic leukemia and acute myeloid leukemia were the major diseases (35.5% and 33.5%, respectively) followed by MDS (29.0%). Given these facts, we emphasize that a greater interest in mycoses should be taken by clinicians, and immunocompromised patients should be protected from opportunistic invasive fungal infections, especially aspergillosis.

Adolescent↗
PubMed1999

A conceptual model of pressure ulcer prevalence: MDS+ items and nutrition.

A conceptual model was developed examining all items in the Minimum Data Set (MDS) as well as serum albumin. This model uses direct and indirect relationships for pressure ulcer prevalence to more adequately plan care, and is suggested as an alternative method of assessment and care planning for pressure ulcer risk. Examination of risk factors using the conceptual model developed will allow nurses to plan individualized care in a cost-effective manner. Linking the MDS to day-to-day care will strengthen its importance in individualized care planning and care provision. Understanding common problems with MDS administration will improve the accuracy of the MDS and will provide a solid basis for nurses to use when making care decisions.

Databases, Factual↗
PubMed2001

[Extraction of RNA from Stored Bone Marrow Smears for Detecting Expression of the WT1 Gene in MDS Patients]

RNA was extracted from stored bone marrow smears, expression of WT1 gene in the patients with MDS was examined by means of nest RT-PCR. The results showed WT1 gene was highly expressed in some cases of MDS. Expression rates were higher in the patients with RAEB and RAEB-t than those patients with RA and RAS. WT1 expression is related to the advance of MDS. The detection of WT1 gene expression by RT-PCR might be useful for assessing disease progress in the patients with MDS.

Journal Article↗
PubMed2004

Treatment of MDS patients with recombinant human erythropoietin and the role of GSTs.

Glutathione S-transferases (GSTs) are a group of enzymes involved in the detoxification process of carcinogens and other substances. The genes encoding isoenzymes M1 and T1 have "null" alleles, which are polymorphic in humans. Our purpose was to examine whether the GSTM1 and GSTT1 homozygous null genotypes have an impact on the response to recombinant human erythropoietin (rhuEpo) treatment in MDS patients. We analyzed lymphocyte DNA samples from 27 patients with all types of myelodysplastic syndromes (MDS) at the time of diagnosis. All patients were scheduled to receive rHuEpo in doses of 150 u/Kg/day for a period of 12 weeks in order to obtain and maintain stable responses. A multiplex polymerase chain reaction (PCR) was used to genotype both GSTM1 and GSTT1 simultaneously, in responders and non-responders to rhuEpo with respect to various pretreatment parameters: haemoglobin, white blood cell count, platelets, serum erythropoietin, transfusion requirements and bone marrow blasts. The data obtained were evaluated by chi2 test and odds ratio were extracted. Twelve out of 27 evaluated patients demonstrated an erythroid response (44%). Nine out of the 12 patients (75%) responding after 12 weeks of treatment had GSTM1 null genotype (OR=3.4). In contrast, only 1 responder (8.3%) was homozygotes of GSTT1 null genotype. Furthermore, no statistically significant difference in the response rate of the different MDS subgroups was observed. Our results suggest that a treatment with rHuEpo may be effective in achieving a stable erythroid response in MDS patients who carry an homozygous deletion of the GSTM1 gene.

Aged↗
PubMed2005

[Effect of recombinant human G-CSF combined with EPO in treatment of patients with MDS].

To investigate the efficaciousness of recombinant human granulocyte colony-stimulating factor (G-CSF) combined with recombinant human erythropoietin (EPO) in the treatment of patients with myelodysplastic syndrome (MDS), the hematological changes in the blood and bone marrow along with clinical features after treatment with G-CSF and EPO in 15 patients were observed. Patients were subcutaneously injected with G-CSF 300 microg/d for 10 days, then injected with EPO 100 U/(kg x d) for 10 days. The results showed that the obvious improvements in granulocytes of blood were found in 10 patients with MDS, improvements in erythrocytes of blood were observed in 7 patients with MDS. No serious side effects occured is all treated patients. In conclusion, treatment of G-CSF in combination with EPO is effective for patients with MDS.

Adult↗
PubMed1990

Cytogenetic abnormalities in 532 patients with myeloid leukemias and myelodyplastic syndrome. The Czechoslovak MDS Cooperative Group.

A total of 170 patients with chronic myeloid leukemia (CML), 107 in chronic phase (CP) and 63 in blastic phase (BP) of the disease, 187 patients with "de novo" acute myelogenous leukemia (AML) and 175 patients with myelodysplastic syndrome (MDS), 164 patients with primary and 11 with secondary MDS, were cytogenetically examined. All patients with CML were Ph positive, additional chromosomal changes were ascertained in 29% of patients in CP and in 71% of patients in BP. The most frequent chromosomal abnormalities were trisomy 8, additional Ph, (i(17q] and loss of Y chromosome. More favorable course of the disease was observed for group of patients with Ph chromosome as solitary chromosomal abnormality in CP. Acquired chromosomal aberrations were proved in 137 patients with AML (73.3%). Except specific chromosomal changes delineated according to the specific subtype of AML we were concerned with evaluation of nonrandom chromosomal abnormalities, specially those involving chromosome 5 and 7. Numerical and morphological changes of those chromosomes were found in 33 patients (17.6%). In MDS patients abnormal chromosomal clones were found in 68.8% of patients, those involving chromosome 5 and/or 7 in 68 patients (38.8% of all examined). The frequency of these abnormalities in AML does not differ significantly from the results quoted by the other studies. However, in our MDS patients these so called "mutagen-associated" chromosome abnormalities were significantly more frequent than in all studies published so far. Prognostic value of cytogenetic examination was evaluated on the basis of cumulative survival of patients with normal and abnormal chromosomal clones present in bone marrow cells.

Adult↗