Myeloma: A malignant disorder of bone and soft tissue
TL;DR: Despite many efforts over the years and the large number of treatment agents introduced, it is apparent that the authors do not have sufficient ability or knowledge to control this very troublesome disorder.
Abstract: The purpose of this brief report is to review a large series of cases of myeloma, a highly malignant tumor. The disease was first described over 150 years ago, but not named myeloma until 1873. The lesion appears to be caused by the production of plasma cells in the bone marrow occasionally associated with amyloid. Patients present with pain in bones, principally spine, pelvis, ribs, calvarium and long bones. The sedimentation rate is elevated and marrow shows 10% plasma cells and the sedimentation rate is always elevated. There is no identified genetic cause and the disease is not familial. The disease has a highly malignant potential. We treated 181 mature adult patients with tumor in multiple sites. 63% were dead of disease at an average of 4.5 years after diagnosis. The use of some new drugs have been helpful, chiefly lalanlidomide or bortezomib. Radiation appears to be useful for some lesions and bisphosphonates sometimes help support the bone structure. Despite many efforts over the years and the large number of treatment agents introduced, it is apparent that we do not have sufficient ability or knowledge to control this very troublesome disorder.
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TL;DR: MEL‐140 is less toxic and appears equally as efficacious as MEL‐200 in elderly patients and the benefits of tandem SCT in this patient population need further evaluation in a randomized trial.
Abstract: The feasibility and efficacy of autologous stem cell transplantation (auto-SCT) in patients aged > or = 70 years was analysed. Newly diagnosed (n = 34) and refractory multiple myeloma (n = 36) patients were studied. The median age was 72 years (range: 70-82.6). CD34+ cells were mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF) (n = 35) or G-CSF alone (n = 35), yielding medians of 11.8 x 10(6) versus 8 x 10(6) cells/kg respectively (P = 0.007). Because of excessive mortality (16%) in the first 25 patients who received melphalan 200 mg/m2 (MEL-200), the dose was subsequently decreased to 140 mg/m2 (MEL-140). Median times to absolute neutrophil count (ANC) > 0.5 x 10(9)/l and to platelets > 20 x 10(9)/l were 11 and 13 d respectively. Thirty-one patients (44%) received tandem auto-SCT. Complete remission (CR) was 20% after the first SCT and 27% after tandem SCT. Median CR duration was 1.5 years and was significantly longer for patients with < or = 12 months of prior chemotherapy (2.6 versus 1.0 years, P = 0.0008). The 3-year event-free survival (EFS) and overall survival (OS) (+ standard error, SE) were projected at 20% + 9% and 31% + 10% respectively. Tandem SCTs positively affected EFS (4.0 versus 0.7 years; P = 0.003) and OS (4.0 versus 1.4 years; P = 0.02) compared with single auto-SCT. In conclusion, MEL-140 is less toxic and appears equally as efficacious as MEL-200 in elderly patients. The benefits of tandem SCT in this patient population need further evaluation in a randomized trial.
210 citations
TL;DR: Although this study suggests that prophylactic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell--depleted BMT and less toxic transplantation strategies are needed to allow a higher proportion of patients to receiveDLI and the benefit from the GVM effect after transplantation.
201 citations
TL;DR: In vivo and in vitro conditions that explain, at least partly, the low aberration rate of cytogenetic abnormalities obtained after banding techniques are focused on.
Abstract: Over the past decade, knowledge of chromosomal aberrations in different types of leukaemias, especially acute leukaemias, has expanded rapidly. The identification of cytogenetic abnormalities has gained considerable importance in the understanding of leukaemia biology as shown by the prognostic impact of specific chromosomal changes (Bloomfield & De la Chapelle, 1987; Secker Walker, 1990). Several factors have hampered similar progress in multiple myeloma (MM), including the fact that karyotypes in MM are often a complex mixture of numeric and structural changes whereas only one cytogenetic change is noticed in many cases of acute leukaemia. Moreover, the low proliferative rate and variable degree of bone marrow infiltration by tumour cells have hampered the discovery of abnormal mitoses. Banding analysis is the only technique that enables a comprehensive assessment of the chromosomal changes present in the metaphase fraction of cell preparations. The main chromosomal changes described so far are related either to stage III disease or to relapsing patients and, as will be discussed below, some of the reported abnormalities are associated with the progression of disease rather than with its emergence. Metaphases, however, are far from being a consistent finding in MM. This review will focus on some of the in vivo and in vitro conditions that explain, at least partly, the low aberration rate of cytogenetic abnormalities obtained after banding techniques. For a better definition of cytogenetic changes in MM, other methods can be used, and will be briefly reviewed. The determination of DNA content within individual cells is one of these methods; it can be assessed with either fluorescent or histologic dyes, and interphase cells can be studied. Techniques using the complementarity of fluorescent DNA probes representative of DNA sequences from a whole chromosome or part of a chromosome, called fluorescence in situ hybridization (FISH), have also been used in MM. In contrast with banding techniques, FISH analysis enables the investigation of metaphase and interphase cells. The recent reports on FISH in MM confirm that a large number of patients bear aneuploid cells. However, FISH depends on the use of specific DNA probes, and only one or a few chromosomes or chromosomal regions can be examined in a single experiment. Whereas an abnormal karyotype is found in approximately 50% of patients, the use of FISH and DNA content of plasma cells demonstrates abnormalities in nearly 90% of MM patients, irrespective of disease status. Recent reports also demonstrate aneuploidy in at least 50% of patients with monoclonal gammopathy of undetermined significance (MGUS), indicating that cytogenetic abnormalities are a very early event in the spectrum of monoclonal gammopathies. Although there is now a considerable amount of data about the advanced stages of the disease, the synergistic use of the newer technologies, together with the improvement of the banding techniques, is needed for a better assessment of chromosomal changes in MM patients, namely for those with indolent stages. A more accurate definition of cytogenetic changes will help towards a better understanding of their significance in the pathogenesis and evolution of this disease.
163 citations
"Myeloma: A malignant disorder of bo..." refers background in this paper
...Published by Sciedu Press 41 pamidronate or zoledronate seem to be helpful in strengthening the bones [57-59] but a recent concern regarding osteonecrosis of the mandible has limited our enthusiasm for the treatment ....
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TL;DR: Evaluation of myeloma bone disease includes plain radiographs, and newer methods, such as magnetic resonance imaging (MRI), positron emission tomography (PET) scans, technetium-99m-sestamibi (Mibi) scanning, and dual-energy x-ray absorptiometry (DEXA)scanning, may provide more complete information.
160 citations