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C Strupp

Publications and source records attributed to C Strupp.

At least 19 recordsLinked to original sources
PubMed2005

Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup.

The survival of patients with myelodysplastic syndromes is strongly affected by chromosomal abnormalities. Patients with an isolated del(5q31) have a favourable prognosis that worsens with the addition of another chromosomal abnormality. It has been reported that both patients with isolated del(5q31) and those with one single additional chromosomal abnormality achieve hematological and cytogenetic remissions with lenalidomide therapy. Whether this translates into improved overall survival of the patient population is unclear. We analysed data of 25 patients with myelodysplastic syndrome and complex chromosomal abnormalities including del(5q31) and show that their median survival is between 7 and 8 months, irrespective of the medullary blast count. Furthermore, we present data of a patient with complex karyotypic anomalies inclusive of del(5q31) treated with lenalidomide who achieved complete cytogenetic remission. This cytogenetic remission was diagnosed after 6 months, and the hematological response is ongoing at 9 months of therapy at a dose of 5 mg p.o. daily. We conclude that lenalidomide has the potential to induce sustained hematological and cytogenetic remissions in the poor prognosis MDS subgroup of del(5q31) patients with complex chromosomal anomalies and that this is likely to improve overall survival.

Adult↗
PubMed2005

Hairy cell leukemia (HCL) with extensive myelofibrosis responds to thalidomide.

We present a 75-year-old man who was admitted to our hospital because of splenomegaly, transfusion-dependent anemia and thrombocytopenia. The diagnosis of idiopathic myelofibrosis was suggested by the bone marrow trephine biopsy, which was hypocellular with myelofibrosis. Thalidomide was started at a daily dose of 100 mg/d and increased to 400 mg/d. Within 12 weeks, thrombocytes increased to 100.000/microl, hemoglobin normalized, lasting for about 11 months. Then, thalidomide had to be discontinued because of mild polyneuropathy. A second bone marrow biopsy showed fibrosis as well as a diffuse infiltration of the bone marrow (80%) by lymphocytes with expression of CD11c, CD19, CD20, CD103. Tartrate resistant acid phosphatase test (TRAP) was also positive. Hairy cell leukemia was diagnosed and he was administered 2-chlorodeoxyadenosine (2-CDA) achieving a complete remission.

Aged↗
PubMed2005

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

Adolescent↗
PubMed2005

The ratio between CD4+ and CD8+ cells in the peripheral blood of patients with hematological malignancies is not altered by thalidomide.

Thalidomide is thought to have anti-angiogenic and immunomodulatory properties, including suppression of tumor necrosis factor-alpha, effects on interleukins and interferons, down-regulation of some cell adhesion molecules, and changes in the proportion of lymphocyte subsets. It is unclear whether the clinical response to thalidomide in patients with multiple myeloma (MM), idiopathic myelofibrosis (IM), and myelodysplastic syndromes (MDS) is related to its ability to inhibit angiogenesis or its immunomodulatory effects. We examined the effect of thalidomide on T-lymphocyte subsets in 18 patients with MDS, 6 patients with MM, 4 patients with IM, and 3 patients with angioimmunoblastic lymphoma (AILD). These patients had either a relapse or progressive disease following cytotoxic chemotherapy including high-dose chemotherapy with autologous stem cell support. Thalidomide was first administered at 100 mg/day p.o. and increased to 400 mg/day. T-lymphocyte subsets (CD4+, CD8+) were measured by fluorescence-activated cell sorter (FACS) before and during treatment with thalidomide. Twenty-six of 31 patients responded to thalidomide, most of them achieving partial remission. The median concentration of CD4+ cells was 443/microl, the median of CD8+ cells was 359/microl (CD3 992/microl). In our cohort, no significant changes in absolute numbers or proportions of CD3+ (P = 0.12), CD4+ (P = 0.668), or CD8+ (P = 0.143) cells were observed following the treatment with thalidomide. Although the CD4/CD8 ratio declined from 1.6 to 1.0 during 3 months of thalidomide treatment, this had no statistical significance (P = 0.1). Our findings show that an effect of thalidomide on the T lymphocytes studied is unlikely to be of major importance for the clinical effects.

Adult↗
PubMed2004

Thalidomide for the treatment of idiopathic myelofibrosis.

Except rare instances of allogeneic stem cell transplantation, treatment of idiopathic myelofibrosis (IMF) is only palliative and based on cytostatic treatment (hydroxyurea and anagrelide), androgen therapy, steroids and splenectomy. Thalidomide is an anti-angiogenic and immunomodulatory drug with a wide spectrum of activities, which are not clearly understood. Current data suggest that the action of thalidomide is related to several different mechanisms, including suppression of tumor necrosis factor, effects on basic fibroblast growth factor, vascular endothelial growth factor, interleukins and interferons, downregulation of selected cell surface adhesion molecules, and changes in the lymphocyte subsets. We administered thalidomide to 16 patients with IMF (15 men, one women) who had transfusion-dependent anemia, thrombocytopenia or symptomatic splenomegaly. Median age was 59 yr (range: 52-78). Patients received thalidomide at an escalating dose from 100 to 400 mg/d (median 300 mg). The drug was discontinued in four patients because of progressive disease (two) or polyneuropathy (two). Other adverse effects were obstipation (10), fatigue (eight) and edema (two). Clinical response has now been observed for a median duration of 9 months (range: 3-20). Fifteen patients are evaluable. Anemia improved in six of 10 patients who were anemic. Platelet counts improved in five of seven patients with thrombocytopenia. Splenomegaly regressed in three of 13 patients. Lactate dehydrogenase (LDH) decreased in seven of 12 patients, but increased in four patients. LDH levels were not correlated with clinical response. In summary, thalidomide appears useful in the treatment of IMF.

Aged↗
PubMed2002

Vertebral fractures in multiple myeloma: first results of assessment of fracture risk using dynamic contrast-enhanced magnetic resonance imaging.

The objective of this study was to evaluate dynamic contrast-enhanced magnetic resonance imaging (d-MRI) as a prognostic indicator of lumbar vertebral fractures in patients with multiple myeloma. d-MRI of the lumbar spine was performed in ten patients with multiple myeloma. A fast gradient echo sequence (turbo fast low-angle shot, two-dimensional) was used, together with controlled bolus injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The maximum increase in signal intensity [amplitude (A),arbitrary units (a.u.)] was assessed for each lumbar vertebra. About half a year later (median: 6.2 months) magnetic resonance imaging was repeated to detect new fractures. Amplitudes of vertebrae which fractured after the initial d-MRI were compared with amplitudes of vertebrae which did not fracture during follow-up. Six of ten patients (7 of 50 lumbar vertebrae) showed new fractures. Five patients fractured one vertebra each, whereas one patient had several vertebrae involved. The initial d-MRI showed significantly higher amplitudes (p<0.0001) in those vertebrae that subsequently fractured (A: 33.1+/-8.1 vs 16.7+/-4.2). On retrospective analysis, a cutoff level of 25 a.u. discriminated without overlap between vertebrae that fractured during follow-up and those which did not. The maximum increase in signal intensity (the amplitude) on d-MRI appears to be a prognostic marker capable of predicting vertebral fractures of the lumbar spine in patients with multiple myeloma. d-MRI may therefore be helpful in identifying patients who might benefit from localized radiation therapy or surgical intervention.

Adult↗
PubMed2002

[Dynamic contrast-enhanced MRI for evaluating bone marrow microcirculation in malignant hematological diseases before and after thalidomide therapy].

PURPOSE: The aim of the study was to measure microcirculation parameters by dynamic contrast-enhanced MRI (d-MRI) and to evaluate the anti-angiogentic effects during treatment with thalidomide in different hematologic malignancies. METHODS: In 20 healthy normal persons, 20 patients with myelodysplastic syndromes (MDS), 10 patients with multiple myeloma (MM) and 10 with myelofibrosis (MF) a fast gradient echo sequence (Turbo fast low angle shot 2D) with a pump controlled bolus infusion of gadolinium-DTPA was performed before and in 18 of these after beginning (average of 4.3 months) of a thalidomide therapy. Two pharmacokinetic parameters--the amplitude and exchange-rate-constant--were calculated and a statistical comparison of these values between healthy persons and patients as well as a correlation with the clinical course was executed. RESULTS: Compared with the normal controls the patients showed a higher amplitude (normal persons 14.4 +/- 5.2, MDS 24.8 +/- 8.1, MF 35.9 +/- 4.3, MM 23.4 +/- 3.6) and exchange-rate-constant (normal persons 0.124 +/- 0.042, MDS 0.136 +/- 0.036, MF 0.144 +/- 0.068, MM 0.131 +/- 0.034). In the d-MRI-follow-up examinations a significant (p < 0.005) reduction of the amplitude and exchange rate constant values was evident in 14 of 18 patients undergoing a thalidomide therapy. Clinically all of these patients showed a therapy responding with complete or partial diseases remission. CONCLUSIONS: In patients with hematologic malignancies significantly higher d-MRI-microcirculation parameters of the lumbar spine can be demonstrated than in normal persons. During anti-angiogenetic treatment with thalidomide a decrease of these values was observed in case of a responding to therapy.

Adult↗
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↗
PubMed2000

Monitoring enzyme catalysis with mass spectrometry.

Mass spectrometry is a rapid, sensitive, and accurate quantitative approach for the direct monitoring of enzyme-catalyzed reactions that does not require a chromophore or radiolabeling and thus provides a viable alternative to existing analytical techniques. In this study the proteolysis of intact viral capsid proteins, the alpha-glucosidase-catalyzed hydrolysis of p-nitrophenyl-alpha-glucopyranoside and the lipoprotein lipase-catalyzed ester hydrolysis of resorufin were examined. Matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry were used to examine the proteolysis of viral protein capsids, providing information about capsid dynamics and the stabilizing force of viral protein/RNA interactions. In addition, k(cat) and K(m) values of enzyme-catalyzed hydrolysis were obtained (without the use of a chromophore). These results also demonstrate the effect an unnatural substrate can have on enzyme activity. Overall, mass spectrometry provides for efficient and quantitative analysis of enzyme-catalyzed reactions, as well as the direct observation of reaction dynamics.

Animals↗
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↗