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ABSTRACT: The prognostic value of chromosomal abnormalities was studied in untreated multiple myeloma patients who were registered into a prospective randomised multicentre phase 3 study for intensified treatment (HOVON24). A total of 453 patients aged less than 66 years with stage II and III A/B disease were registered in the clinical study. Cytogenetic analysis was introduced as a standard diagnostic assay in 1998. It was performed at diagnosis in 160 patients and was successful in 137/160 patients (86%). An abnormal karyotype was observed in 53/137 (39%) of the patients. Abnormalities of chromosome 1p and 1q were found in 19 (36% of patients with an abnormal karyotype) and 21 patients (40%). There was a strong association between chromosome 1p and/or 1q abnormalities and deletion of chromosome 13 or 13q (n = 27, P < 0.001). Patients with karyotypic abnormalities had a significantly shorter overall survival (OS) than patients with normal karyotypes. Complex abnormalities, hypodiploidy, chromosome 1p abnormalities, chromosome 1q abnormalities, and chromosome 13 abnormalities were associated with inferior OS on univariate analysis, as well as after adjustment for other prognostic factors. In conclusion, chromosome 13 abnormalities and chromosome 1p and/or 1q abnormalities were highly associated, and are risk factors for poor outcome after intensive therapy in multiple myeloma.
British Journal of Haematology 03/2007; 136(4):615-23. · 4.94 Impact Factor
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ABSTRACT: Several chromosomal aberrations have been associated with molecular pathogenesis and classification of multiple myeloma. It is not known whether the expression of abnormal karyotypes is consistent in patients during disease progression. Herein, we report on sequential analysis of conventional cytogenetics as well as fluorescence in situ hybridization (FISH) data of 79 bone marrow specimens from 38 patients with myeloma who were longitudinally followed.
We determined and characterized the development of additional chromosomal aberrations during progressive disease.
Overall, conventional cytogenetics detected an abnormal karyotype in 42% of the samples, whereas this increased to 69% by FISH. Among the cases with an abnormal conventional karyotype, 52% had a hyperdiploid subtype of myeloma. Progressive disease was correlated with an increased complexity of genetic abnormalities, which in the majority, consisted of structural aberrations acquired in later stages of disease. Using conventional cytogenetics, rearrangements of chromosome 1 were the most common structural abnormality (15%). In the majority, these rearrangements consisted of unbalanced translocations of 1p and 1q; however, no specific locus was predominantly affected. Second in frequency were structural aberrations of chromosomes 8 and 17 (6%). The frequency of del(13q) by FISH was 40% and did not increase in later stages of the disease, suggesting that del(13q) is not a genetic event associated with disease progression. Change of ploidy category during disease progression occurred in a minority of the cases.
This study supports the notion that cytogenetic abnormalities in multiple myeloma are not random. Particular chromosomal alterations are associated with disease progression, whereas others show a stable pattern during the course of the disease.
Clinical Lymphoma & Myeloma 02/2007; 7(4):280-5. · 1.13 Impact Factor
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ABSTRACT: Arsenic trioxide induces growth inhibition and apoptosis in multiple myeloma cell lines. Reducing glutathione by ascorbic acid may enhance the efficacy of arsenic trioxide. Here we report the results of an international multi-center study of arsenic trioxide in combination with ascorbic acid and dexamethasone as treatment for patients with advanced multiple myeloma.
Haematologica 01/2007; 91(12):1722-3. · 6.42 Impact Factor
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ABSTRACT: The clinical course and histologic findings of cutaneous adverse reactions associated with bortezomib treatment are presented in this study. Bortezomib (Velcade) is a proteasome inhibitor, which is used as a novel anticancer drug in the treatment of multiple myeloma. We have conducted an observational analysis of 47 patients with myeloma who were treated with bortezomib in 3 prospective clinical trials. Cutaneous adverse reactions were observed in 6 patients (13%). Five patients presented with sharply demarcated erythematous plaques or nodules on the trunk and one patient had generalized morbilliform erythema with ulcerations and fever. The time between the first bortezomib dose and occurrence of the cutaneous eruptions was at least 30 days. The cutaneous eruptions usually resolve within a few days. One patient withdrew from further treatment because of severe cutaneous toxicity. The histologic findings ranged from perivascular dermatitis to interstitial and interface dermatitis corresponding with clinically more extensive lesions.
Journal of the American Academy of Dermatology 12/2006; 55(5):897-900. · 3.99 Impact Factor
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Neurology 09/2006; 67(4):722-3. · 8.31 Impact Factor
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ABSTRACT: The application of high-dose therapy combined with stem cell support has greatly improved the outcome of treatment in patients with multiple myeloma. However, induction treatments are rapidly changing, and it has now become possible to achieve complete responses in 30%-40% of newly diagnosed patients before high-dose therapy. The effect of the improved induction regimens on the results of the whole treatment strategy and the long-term outcome will have to be evaluated in prospective randomized trials. The introduction of new drugs such as thalidomide and bortezomib have contributed significantly to this changed remission status and may ultimately lead to a change of concept about the value of remission-induction therapy. In this article, we review various regimens that are used for induction therapy in preparation for stem cell transplantation and describe the impact these novel agents could have on patient remission status.
Clinical Lymphoma & Myeloma 10/2005; 6(2):96-101. · 1.13 Impact Factor
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ABSTRACT: The clinical data on the efficacy and toxicity of bortezomib as treatment for multiple myeloma patients are restricted to prospective phase II studies in expert myeloma centers. Here we report a multi-institutional analysis of the efficacy and toxicity of bortezomib in patients with relapsed or refractory multiple myeloma who were treated in community centers in a compassionate need program.
Haematologica 08/2005; 90(7):996-7. · 6.42 Impact Factor
