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N Gattermann

Publications and source records attributed to N Gattermann.

At least 37 records · Page 2Linked to original sources
PubMed2002

Favourable response to antithymocyte or antilymphocyte globulin in low-risk myelodysplastic syndrome patients with a 'non-clonal' pattern of X-chromosome inactivation in bone marrow cells.

OBJECTIVE: Antithymocyte and antilymphocyte globulin (ATG/ALG) have a therapeutic effect in about 30% of patients with myelodysplastic syndromes (MDS). We were interested to know whether responding patients achieve clonal or polyclonal remissions. PATIENTS: Ten women with low-risk MDS received either ALG or ATG. Before treatment and 3, 6, and 12 months later, X-chromosome inactivation patterns of peripheral blood T lymphocytes were compared with those of peripheral blood granulocytes or bone marrow cells, using the human androgen receptor gene assay and the phosphoglycerate kinase-1 assay. RESULTS: Six women did not respond to therapy. Prior to treatment, four of them had a monoclonal, one had an oligoclonal, and one had a skewed X-chromosome inactivation pattern (XCIP). Four patients responded to ATG/ALG. Three of them were informative in our X-inactivation assays, and showed a non-clonal XCIP which did not change significantly after treatment with ATG/ALG. CONCLUSION: A non-clonal XCIP in the bone marrow was associated with a response to ATG/ALG. Non-clonal XCIPs do not necessarily imply that there is no pathological clone. By definition, they just indicate that there is no evidence of a clone contributing more than 50% of cells in a sample. Non-clonal XCIPs may therefore be attributable to incomplete clonal expansion. This, in turn, might be explained by a vigorous immune attack against the MDS clone, which simultaneously causes collateral damage in the remaining normal haemopoiesis. In such patients, ATG/ALG may improve normal haemopoiesis by relieving the immunological pressure on the innocent bystanders.

Aged↗
PubMed2002

Thalidomide for the treatment of patients with myelodysplastic syndromes.

We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA. Patients belonged to the following cytogenetic groups: 15 complex abnormal karyotypes, 12 normal karyotypes, four cases with 5q- as sole anomaly and three single aberrations. The median thalidomide dose was 400 mg/day (25/34 patients). Four patients discontinued the study after less than 5 weeks, because of fatigue (three) or skin rash (one). One patient died of heart failure after 4 weeks. In the remaining 29 patients (median follow-up: 13 months), treatment responses were classified according to the IWG criteria. Six patients (four RA, two CMML) showed progressive disease (five with transformation into AML) and four patients showed stable disease. Hematological improvement (HI) was observed in 19 patients. Nine of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial remission with granulocytes > or = 1500/microl, Hb > 11 g/dl and platelets > or =100,000/microl. Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a major response, with platelet and RBC transfusion independence. Six patients (five RA, one RARS) showed minor responses (three HI-E, two HI-E+HI-P, one HI-E+HI-N). Hematological improvement occurred after a median of 2 months of thalidomide treatment. Two patients (RAEB-T) relapsed after a partial remission lasting 8 and 16 months, respectively. In summary, a therapeutic benefit was achieved in 19 of 34 study patients (56%).

Aged↗
PubMed2002

[Dynamic MRI of the lumbar spine for the evaluation of microcirculation during anti-angiogenetic therapy in patients with myelodysplastic syndromes].

PURPOSE: Evaluation of MRI perfusion parameters of the lumbar spine in patients with myelodysplastic syndromes (MDS) to determine the vascularisation and anti-angiogenetic effects of thalidomide therapy. MATERIAL AND METHODS: In 20 healthy normal persons and 28 MDS patients a dynamic contrast-enhanced MRI (d-MRI) of the lumbar spine was performed. After the initial d-MRI-investigation 24 of the 28 MDS patients received an anti-angiogenetic therapy with thalidomide. With an average of 4.2 months after the beginning of therapy a d-MRI-follow-up examination in 9 of these patients was performed. The amplitude and exchange-rate constant were calculated and a statistical comparison of these values between healthy persons and MDS patients as well as a correlation with the clinical course was executed. RESULTS: Compared with the normal controls the MDS patients showed a higher amplitude (normal persons: 14.4 +/- 5.2, MDS: 24.8 +/- 8.1) and exchange-rate constant (normal persons: 0.124 +/- 0.042, MDS: 0.136 +/- 0.036). In 7 of 9 MDS patients undergoing thalidomide therapy a reduction of the amplitude and exchange rate constant values was evident in the d-MRI follow-up examinations. Clinically these patients showed a therapy response with complete or partial disease remission. CONCLUSIONS: In MDS patients significantly higher d-MRI parameters can be demonstrated than in normal persons. Under anti-angiogenetic treatment these values decrease in case of a response to therapy. Thus, d-MRI seems suitable for the evaluation of anti-angiogenetic therapy effects.

Adult↗
PubMed2002

[Does dynamic contrast-enhanced MRI enable recognition of development of vertebral fractures in multiple myeloma?].

PURPOSE: To compare the value of MRI sequences with dynamic MRI measurements (d-MRT) for the assessment of risk of lumbar vertebral fractures in patients with multiple myeloma. MATERIAL AND METHODS: In 10 patients with multiple myeloma a sagittal T 1 -, T 2 -weighted spin-echo and an inversion-recovery sequence were performed. For dynamic measurements a fast gradient-echo sequence (turbo fast low angle shot 2 D) with machine-controlled Gd-DTPA administration was used. The presence of bone marrow abnormalities was determined and additionally the value of the highest signal increase (amplitude Alpha) was calculated for each of the 50 vertebral bodies. The subsequent development of vertebral fractures was assessed by MRI at a mean time interval of 6.2 months after the initial d-MRI. The pattern of marrow involvement and the amplitudes of the vertebral bodies that collapsed in the observation period were statistically compared with those of the vertebral bodies that did not collapse. RESULTS: During the follow-up period newly or progressive fractures occurred in 6 of 10 patients (7 of 50 vertebral bodies). The degree of pathological signal changes that preceded fractures was not significantly different (p > 0.05) from that of the other contemporary lesions identified in vertebral bodies that did not collapse in follow-up. In contrast, the amplitude of vertebrae that collapsed (A: 33.1 +/- 8.2) was significantly higher (p < 0.0001) than the amplitude of vertebrae that did not collapse (A: 16.7 +/- 4.2). The amplitude was a reliable predictor of vertebrae that collapsed in all cases. CONCLUSION: In contrast to the analysis of marrow lesions detected with non-dynamic MRI, this study suggests that the perfusion-parameter amplitude in dynamic contrast-enhanced MRI is a potentially relevant value to predict the risk of vertebral fractures in patients with multiple myeloma.

Adult↗
PubMed2002

Angioimmunoblastic lymphadenopathy (AILD) may respond to thalidomide treatment: two case reports.

The histological morphology of AILD-type T-cell lymphoma shows proliferation of small, arborizing high endothelial venules. Patients typically have generalized lymphadenopathy, fever, weight loss, skin rash, polyclonal hypergammaglobulinemia and autoimmune phenomena, and are susceptible to infections. The clinical course is usually aggressive. About 30% of patients have an initial remission on steroids alone, but most require some form of cytotoxic chemotherapy. Median survival ranges from 15 to 24 months, and it appears that the disease cannot be cured. We have used anti-angiogenetic therapy with thalidomide in two AILD patients and observed remarkable responses.

Adolescent↗
PubMed2001

[Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction].

OBJECTIVE: The regenerative potential of human autologous adult stem cells on myocardial regeneration and neovascularisation after myocardial infarction may contribute to healing of the infarction area. But no clinical application has previously been reported. We here describe for the first time the results of this method applied in a patient who had sustained an acute myocardial infarction. HISTORY AND CLINICAL FINDINGS: 14 hours after the onset of left precordial pain a 46-year-old man was admitted to our hospital for interventional diagnosis and treatment. Coronary angiography demonstrated occlusion of the anterior descending branch of the left coronary artery with transmural infarction. This was treated by percutaneous transluminal catheter angioplasty and stent placement. THERAPY AND RESULTS: Mononuclear bone marrow cells of the patient were prepared and 6 days after infaction 1,2 infinity 107 cells were transplanted at low pressure via a percutaneous transluminal catheter placed in the infarct-related artery. Before and 10 weeks after this procedure left ventricular function, infarct size, ventricular geometry and myocardial perfusion were measured by (201)thallium SPECT both at rest and on exercise, together with bull's-eye analysis, dobutamine stress echocardiography, right heart catheterisation and radionuclide ventriculography. At 10 weeks after the stem cell transplantation the transmural infarct area had been reduced from 24.6 % to 15.7 % of left ventricular circumference, while ejection fraction, cardiac index and stroke volume had increased by 20-30 %. On exercise the end diastolic volume had decreased by 30 % and there was a comparable fall in left ventricular filling pressure (mean pulmonary capillary pressure). CONCLUSION: These results for the first time demonstrate that selective intracoronary transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after transmural infarction. The therapeutic effects may be ascribed to stem cell-associated myocardial regeneration and neovascularisation.

Angioplasty, Balloon, Coronary↗
PubMed2001

Hemoglobinopathy York [beta146 (HC3) His==>Pro]: first report of a family history.

The rare hemoglobinopathies with abnormal oxygen binding are usually characterized by erythropoietin-mediated erythrocytosis. Bare et al. first described a hemoglobinopathy with mild erythrocytosis in a 22-year-old Caucasian woman in 1976. These authors called the abnormal hemoglobin Hb York. Hb York is characterized by a mutation at the beta146 position that changes histidine into proline. A second case of Hb York was observed by Kosugi et al. in 1983. To the best of our knowledge, no further cases have been reported. We have encountered a new case of Hb York, which was detected by agar gel electrophoresis at pH 6.0. Analysis of DNA sequences revealed a CAC-->CCC mutation in codon 146. The proportion of Hb York was approximately 50%. Analysis of oxygen transport function showed a leftward shift of the sigmoidal O2-dissociation curve. P50 was reduced to 15.5 mmHg. Investigation of family members revealed Hb York in the patient's sister, two daughters and a grandson. In retrospect, the mother of the patient may also have been affected. The mode of inheritance is autosomal dominant.

Aged↗
PubMed2001

Secondary myelodysplastic syndrome after fludarabine therapy of a low-grade non-Hodgkin's lymphoma.

We diagnosed a probable fludarabine-induced secondary MDS approximately 18 months after treatment of a low grade non-Hodgkin's lymphoma. After diagnosis of a B-cell lymphoma composed of relatively small cells, fludarabine was administered between May and October, 1997, to a 64-year-old female patient. In December 1998, a mild bicytopenia was present with a leukocyte count of 3800/microl and platelets of 142000/microl. The white cell differential count was normal. The hemoglobin level was normal, but MCV was elevated. Bone marrow cytology revealed normal cellularity with dyserythropoiesis and dysmegakaryocytopoiesis. PAS staining showed scattered positivity in early erythroid cells. In 12 of 20 mitoses, the karyotype showed complex rearrangements, described as 46,XX,t(4;11)(q23?24;q13),del(5q),del(7)(q22),+mar[8]/45,-3. A diagnosis of treatment-related MDS was made. While there was no evidence of bone marrow infiltration by the lymphoma, CT scans demonstrated paraaortic lymph nodes up to 10 cm in diameter. After one course of CHOP chemotherapy, prolonged bone marrow aplasia and septic complications occurred. Chemotherapy was abandoned and Rituximab was administered. In July and November, 1999, bilateral pneumonia and urinary tract infection, respectively, were treated with antibiotics. NHL was in complete remission, but peripheral blood counts deteriorated markedly, and transfusions of packed red cells had to be started in November, 1999. The suspicion of leukemic transformation could not be confirmed because the patient declined further bone marrow biopsies. In December, 1999, the patient died from pneumonia.

Antineoplastic Agents↗
PubMed2000

Pericardial effusion in chronic myelomonocytic leukemia (CMML): a case report and review of the literature.

Pericardial effusion is a rare but potentially life-threatening complication of chronic myelomonocytic leukemia. A case of a 70-year-old female with CMML is reported, who developed a severe pericardial effusion after an initially stable course of disease. She underwent pericardiocentesis and subsequent intracardial instillation of mitoxantrone with poor response. Subxiphoid pericardiotomy was successfully performed. Leukocytosis did not respond to hydroxyurea. Because of decreasing performance status of the patient systemic chemotherapy was not applied and the patient died within 2 weeks. A review of the literature shows that there is no effective treatment for pericardial effusion in CMML, and some common features may be noted.

Aged↗
PubMed2000

Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients.

In 1982, the French-American-British (FAB) cooperative group proposed a classification of myelodysplastic syndromes (MDS) based on morphological features in blood and bone marrow, namely on medullary and peripheral blast count, Auer rods, ring sideroblasts and the number of monocytes in the peripheral blood. This classification has been used for numerous studies regarding morphology, prognosis and treatment of MDS. Some details of this morphological classification remained unclear, and some patients were unclassifiable. A working group of the World Health Organization (WHO) recently proposed a new classification of MDS, based on a significant modification of the original FAB proposals. CMML and RAEB-T were removed from the MDS classification and RAEB was split into two groups with medullary blast counts below and above 10%. In addition, a group of patients with less than 5% medullary blasts but evidence of multilineage dysplasia was defined. MDS patients with 5q- as the sole chromosomal anomaly were also considered a separate group. The aim of the present study was to validate the new classification with respect to prognostic importance, and to correlate it with cytogenetic and hematological features in a large series of patients (n=1600) with a long-term follow up. We were able to confirm a significant difference in prognosis between RAEB I and RAEB II, as well as a difference between refractory anemia and multilineage dysplasia. Furthermore, patients with 5q- anomaly had a much better prognosis than other WHO subtypes, but this was only true for patients with a medullary blast count below 5%. In summary, the WHO classification appears to define morphological subgroups that are more homogeneous with respect to prognosis than the FAB subtypes.

Adolescent↗
PubMed2000

From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes.

A primary mitochondrial defect may be pivotal in the pathogenesis of acquired idiopathic sideroblastic anemia (AISA). The mitochondrial respiratory chain is involved in mitochondrial iron uptake and supply of ferrous iron (Fe2+) for heme synthesis. Mitochondrial DNA (mtDNA) comes into play because several subunits of the respiratory chain are encoded by the mitochondrial genome. We have identified heteroplasmic mutations of mtDNA, which may not only impair mitochondrial iron metabolism and heme synthesis, but through impairment of mitochondrial energy production may have much broader implications for MDS pathogenesis. For example, increased apoptosis and genetic instability may be phenomena linked to mitochondrial dysfunction.

Anemia, Sideroblastic↗
PubMed2000

Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction.

In 1982, acquired idiopathic sideroblastic anaemia (AISA) was included by the French-American-British (FAB) Co-operative Group in their classification of myelodysplastic syndromes (MDS). However, the malignant potentiality of AISA has always been a matter of debate. In different series, median survival and rates of transformation into acute myeloid leukaemia (AML) varied extensively. On cytomorphological grounds, AISA can be divided into pure (dyserythropoietic) sideroblastic anaemia (PSA), in which dysplasia is confined to erythropoietic cells, and a true myelodysplastic form (RARS), which is characterized by additional dysplastic features of granulopoiesis and/or megakaryopoiesis. In a previous study, based on retrospective analysis of 94 patients with AISA, we found that both types of sideroblastic anaemia differed considerably in terms of survival and risk of AML transformation. Almost identical results have now been obtained through a prospective study of 232 new patients with AISA. The difference in survival between PSA and RARS remained significant over the whole period of follow-up (survival after 3 years being 77% vs. 56%; P = 0.003), and the incidence of AML did not increase with time in the PSA group, even in the long term. This prospective study strongly supported our conclusion that cytomorphological distinction between PSA and RARS provides valuable prognostic information.

Adult↗
PubMed2000

Long-term remission after intensive chemotherapy in advanced myelodysplastic syndromes is generally associated with restoration of polyclonal haemopoiesis.

The clonality of peripheral blood cells was assessed in eight female patients with myelodysplastic syndrome (MDS) by means of the human androgen receptor gene-based assay (HUMARA). The patients were in complete remission for a median follow-up time of 83 months after intensive chemotherapy. X-chromosome inactivation patterns (XCIPs) indicated polyclonal haemopoiesis in five patients. Two patients had skewed lyonization (i.e. unbalanced XCIPs in both granulocytes and T cells) and one patient presented monoclonal granulocytes together with polyclonal T cells. We conclude that long-term remission in MDS following intensive chemotherapy is usually associated with polyclonal haemopoiesis.

Adult↗
PubMed1999

[Role of aggressive treatment strategies for myelodysplastic syndromes].

Myelodysplastic syndromes (MDS) constitute a heterogenous group of acquired bone marrow disorders characterized by ineffective hematopoiesis, cellular dysfunction and an increased risk of transformation into acute myeloid leukemia (AML). The percentage of medullary blast cells and the karyotype at diagnosis are the most important predictors of survival. Patients with more than 10% blast cells or an unfavourable karyotype (chromosome 7 abnormalities or complex aberrations) usually survive less than 12 months. This review article focuses on the roles of intensive AML-type chemotherapy, autologous stem cell transplantation and allogeneic bone marrow transplantation in the management of patients with advanced MDS. Recent studies suggest that, with appropriate selection of patients, intensive chemotherapy produces high rates of complete remission. Chances of entering remission are particularly high in patients with a good Karnofsky score, bone marrow blast count < 30% and normal karyotype. When compared with acute myeloid leukemia, results of autologous bone marrow transplantation in MDS are disappointing. A major disadvantage of this approach is the delayed recovery of hematopoiesis. Autologous peripheral blood progenitor cell transplantation overcomes this difficulty and is currently explored as consolidation therapy after successful remission induction with polychemotherapy in an intergroup study of the EORTC and EBMT. Allogeneic bone marrow transplantation remains the treatment of choice for younger MDS patients, offering a good chance of cure if the transplantation is performed at an early stage of disease or if the patient receives the transplant in complete remission after conventional chemotherapy.

Humans↗