Biomedical subjects

J Hillengass

Publications and source records attributed to J Hillengass.

6 recordsLinked to original sources

PubMed2006

Thalidomide in multiple myeloma.

Thalidomide (Thal) has antiangiogenic and immunomodulatory activity. Clinical research provided clear evidence that Thal is one of the most active drugs for the treatment of multiple myeloma leading to decrease of monoclonal protein of at least 50 % in 30 % of patients with relapsed or refractory multiple myeloma. Randomized trials based on a large body of evidence from phase II trials determined that Thal significantly increases total response rate in combination regimens (dexamethasone [Dex] and or chemotherapy) for relapsed as well as newly diagnosed patients. Thal also decreases time to response in combination therapy approaches. Thal has therefore been recognized by leading organizations as part of the treatment concept for patients with relapsed or refractory disease. Strict guidelines apply for the treatment and monitoring of Thal therapy to prevent the teratogenic effects of Thal and to monitor and prevent other potential adverse events as neuropathy and thrombosis. Additional randomized studies will now define the status of Thal for newly diagnosed patients and will be the basis for the approval in Europe and other countries world wide.

Angiogenesis Inhibitors↗

PubMed2004

[Dynamic MRI of the bone marrow for monitoring multiple myeloma during treatment with thalidomide as monotherapy or in combination with CED chemotherapy].

PURPOSE: To quantify changes of bone marrow microcirculation in multiple myeloma (MM) using contrast enhanced dynamic MRI (dMRI) during thalidomide as antiangiogenic monotherapy or in combination with chemotherapy (cyclophosphamide, etoposide, dexamethasone). MATERIALS AND METHODS: The study includes 63 patients with refractory or relapsed MM, who underwent dMRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine before and following treatment. The contrast uptake was quantified using a two compartment model with the output parameters amplitude and k (ep) (exchange rate constant). The evaluation considered the initial dMRI finding (pathological or non-pathological) and the clinical therapeutic response (response or no response). RESULTS: During monotherapy with thalidomide (n = 38), no significant changes of the dMRI parameters were found, even when considering the initial dMRI finding (positive n = 22) and the therapeutic response (responder n = 14). The combination with chemotherapy (n = 25) had a significant reduction of k (ep) (p = 0.01) in 18 patients with positive initial dMRI finding and therapeutic response. Reduction of the amplitude was seen in most cases, but in the end without any significance (p = 0.09). CONCLUSION: dMRI can quantify significant changes of bone marrow microcirculation solely during treatment with thalidomide combined with chemotherapy, not with thalidomide alone.

Administration, Oral↗

PubMed2004

Antiangiogenic therapy in hematologic malignancies.

Angiogenesis is defined as the formation of new capillaries from prexisting blood vessels and plays an important role in the progression of solid tumors and hematologic malignancies. Markers of angiogenesis correlate with clinical characteristics in leukemia and non-Hodgkin's-lymphoma, serving as predictors of poor prognosis. Antiangiogenic effects of chemotherapeutics as well as of novel drugs such as farnesyltransferase inhibitors and tyrosine kinase inhibitors such as Gleevec might contribute to their therapeutic potential. Thalidomide which has antiangiogenic effects and direct cytotoxic effects was found to be effective in multiple myeloma and is considered as an established treatment modality for patients with refractory or relapsed multiple myeloma. Thalidomide has a significant therapeutic effect in myelodysplastic syndrome (MDS) by improving cytopenia and achieving independence of transfusion therapy in a subset of patients. Preliminary data indicate activity of specific VEGF receptor tyrosine kinase (RTK) inhibitors in multiple myeloma (MM) and acute myeloid leukemia (AML). The positive correlation between increased levels of angiogenic cytokines and clinical response to VEGF-RTK inhibitors and thalidomide indicates the relevance of detecting angiogenesis markers to identify best candidate patients for specific approaches. Including antiangiogenic drugs into treatment protocols for hematologic malignancies is an important task for future clinical studies.

Angiogenesis Inhibitors↗

PubMed2001

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging.

The aim of our study was to investigate the quantitative microcirculation parameters amplitude A (hypothetical intravascular volume) and exchange rate constant k(21) (hypothetical vascular permeability) by contrast-enhanced dynamic magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal controls and 41 patients with active MM were assessed using a dMRI protocol with a pump controlled bolus infusion of Gadolinium-DTPA. Pharmacokinetic parameters, amplitude A and exchange rate constant k(21) were calculated according to a 2-compartment model. Color-coded parameter images were generated from pharmacokinetic data analysis and superimposed onto the conventional MR images. Amplitude A and k(21) parameters were significantly increased in patients with MM compared with controls (p = 0.001; median A(ctr), 0.2 [range, 0.09-0.4]; median A(MM), 0.93 [range, 0.2-2.2]; median k(21ctr), 0.09 min(-1) [range, 0.03-0.9]; median k(21MM), 4.58 [range, 0.22-23.8]). Within the group of MM patients the pattern of color-coded parameter images were found to be either of "diffuse" (n = 13, 31%) or "focal" (n = 28, 69%) type of distribution of microcirculation. Comparison of amplitude A in patients with "focal" vs. "diffuse" pattern of the pharmacokinetic maps revealed a significant increase in the median of amplitude A in the "focal" group. Amplitude A values allowed a classification of patients according to severe osteolytic bone involvement (p = 0.023) with the best cutoff value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is a novel imaging technique for the detection and monitoring of MM bone lesions. It provides independent evidence for angiogenesis in MM.

Adult↗

PubMed2001

High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma.

The aim of this study was to define prognostic factors that might be predictive for response to thalidomide (Thal) in progressive multiple myeloma (n = 54). We examined the concentration of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), two potent heparin-binding mediators of angiogenesis in peripheral blood (PB; PB-VEGF and PB-bFGF) and bone marrow (BM; BM-VEGF and BM-bFGF), in combination with well-characterized predictors for response and survival to chemotherapy. After a median follow-up time of 15 months (range, 0.3-20), 29 patients (pts.) showed at least a minimal response to Thal therapy, whereas 25 pts. were nonresponsive. As shown by univariate analysis, responsive pts. had statistically significant higher concentrations of PB-bFGF (P = 0.009) and beta2-microglobulin (P = 0.03) before therapy, as well as lower hemoglobin (P = 0.008) and albumin (P = 0.02) levels, whereas no statistically significant difference was found for PB-VEGF (P = 0.93). When a multiple logistic regression analysis was performed, PB-bFGF was the only statistically significant predictor for response to therapy (P = 0.01). None of these variables was associated with a prolonged progression-free survival. In conclusion, our findings indicate that high pretreatment plasma bFGF levels in pts. with progressive multiple myeloma are associated with unfavorable parameters of response and survival but nevertheless predict for response to Thal therapy.

Adult↗

PubMed2000

[Functional magnetic resonance tomography in the diagnosis and therapy monitoring in multiple myeloma].

AIM OF THE STUDY: Investigation of the quantitative microcirculation parameters amplitude A and exchange rate constant k21 determined by contrast-enhanced dynamic magnetic resonance imaging (d-MRI) in multiple myeloma (MM). METHODS: d-MRT of lumbar spine and right spina iliaca superior posterior of 16 controls (ctr) and 35 patients with active MM. Generation of colour-coded images of microcirculation parameters superimposed onto static MRI images. RESULTS: Amplitude A and k21 parameters were significantly increased in patients with MM and down modulated by therapy in 7 of 8 MM cases in a follow-up investigation [p < 0.01; median Actr = 0.2 (0.09-0.4); median AMM = 0.93 (0.2-1.52); median k21ctr = 0.09 min-1 (0.03-0.9); median k21MM = 4.57 min-1 (0.21-23.8)]. Thirteen patients revealed a "diffuse" and 22 a "focal" pattern of distribution of microcirculation parameters. Bone marrow biopsies in 8 cases revealed an correlation between bone marrow plasma cell infiltration and increased microcirculation parameters. CONCLUSION: Identification of microcirculation changes by d-MRI is a novel imaging technique for the detection and monitoring of MM bone lesions.

Antineoplastic Agents, Alkylating↗