Biology, Clinical Patterns, and Treatment of Multiple Myeloma and Related Plasma–Cell Dyscrasias

Farhangi, Mehdi; Osserman, Elliott F.

doi:10.1007/978-1-4613-4015-7_22

Cited by 10 publications

(6 citation statements)

References 370 publications

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“…BMT usually reduces rather than stimulates normal bone mineralization. [28][29][30] Also, osteolytic lesions in myeloma patients do not respond to high does of alkylating agents, but the lesions can be successfully managed with bisphosphonate therapy, 31 which indicates that the alkylating agents received by our patients probably did not significantly inhibit osteoclast function. Finally, there is no evidence that bone marrow conditioning regimens can stimulate linear growth.…”

Section: Discussionmentioning

confidence: 84%

Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta

Horwitz

Prockop

Gordon

et al. 2001

Blood

515

353

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Preclinical models have shown that transplantation of marrow mesenchymal cells has the potential to correct inherited disorders of bone, cartilage, and muscle. The report describes clinical responses of the first children to undergo allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta (OI), a genetic disorder characterized by defective type I collagen, osteopenia, bone fragility, severe bony deformities, and growth retardation. Five children with severe OI were enrolled in a study of BMT from human leukocyte antigen (HLA)-compatible sibling donors. Linear growth, bone mineralization, and fracture rate were taken as measures of treatment response. The 3 children with documented donor osteoblast engraftment had a median 7.5-cm increase in body length (range, 6.5-8.0 cm) 6 months after transplantation compared with 1.25 cm (range, 1.0-1.5 cm) for age-matched control patients. These patients gained 21.0 to 65.3 g total body bone mineral content by 3 months after treatment or 45% to 77% of their baseline values. With extended follow-up, the patients' growth rates either slowed or reached a plateau phase. Bone mineral content continued to increase at a rate similar to that for weight-matched healthy children, even as growth rates declined. These results suggest that BMT from HLA-compatible donors may benefit children with severe OI. IntroductionBone marrow mesenchymal cells can differentiate to a variety of tissues including bone, cartilage, muscle, and fat. 1-7 Thus, in principle, bone marrow transplantation (BMT) could provide effective therapy for disorders that involve cells derived from mesenchymal precursors. 8 One attractive candidate is osteogenesis imperfecta (OI) or "brittle bone disease," a genetic disorder caused by defects in type I collagen, the major structural protein of the extracellular matrix of bone. [9][10][11] Patients with severe OI have numerous painful fractures, progressive deformities of the limbs and spine, retarded bone growth, and short stature. There is no cure for OI, and only one class of drugs, the bisphosphonates, which can reduce or prevent bone resorption, appear to have therapeutic potential. [12][13][14] Ideally, therapy for OI should be directed toward improving bone strength by improving the structural integrity of collagen and thereby the quality of the bone. 15,16 Although the existence of circulating osteoblast progenitors is controversial, 17 preclinical studies have demonstrated that whole bone marrow contains cells that can engraft and become competent osteoblasts after transplantation. 18 Moreover, because collagen is a secreted product, even a low level of osteoblast engraftment might be beneficial to OI patients. 6,19 Guided by this rationale, we undertook a pilot study to demonstrate the feasibility of transplanting bone marrow-derived mesenchymal cells in children with OI.Although providing a basis for continued testing of this strategy, our initial analysis 20 included only 6 months of clinical follow-up and did not directly compare resul...

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Section: Discussionmentioning

confidence: 84%

Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta

Horwitz

Prockop

Gordon

et al. 2001

Blood

515

353

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“…this variant had been reported by 1974 (Jancelewicz et al, 1975) and only a few additional cases have been documented (Kyle, 1975;Isobe et al, 1976;Farhangi and Osserman, 1978;Schulman et al, 1980). The age of onset is lower and the median survival time (about 9 months) is shorter than has been reported for non-IgD myeloma patients.…”

Section: Discussionmentioning

confidence: 93%

“…IgD myeloma is sufficiently distinct from other sub-groups of MMy and it is relatively uncommon, representing only 0.6 to 3 per cent of all cases of MMy (Zawadzki and Edwards, 1967;Fahey et al, 1968;Hobbs and Corbett, 1969;Fishkin et al, 1970;Jancelewicz et al, 1975;Kyle, 1975;Farhangi and Osserman, 1978).…”

mentioning

confidence: 96%

Late occurrence of IgD myeloma in plasmacytoma of nasal cavity, cervical lymph node and larynx

et al. 1982

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“…Thus, hyperviscosity syndrome is most common in Waldenstrom's macroglobulinemia, followed by IgA myeloma because of the frequent polymerization of the IgA paraprotein. [83][84][85] In the case of IgM, the serum viscosity is proportional to the plasma concentration of this paraprotein up to 3 g/dL, then increases sharply at higher levels. In IgG myeloma with hyperviscosity syndrome, the paraprotein is usually that of IgG-3 class, as IgG-3 tends to form aggregates and complexes.…”

Section: Multiple Myelomamentioning

confidence: 99%

The Hyperviscosity Syndromes

Kwaan¹,

Bongu²

1999

Semin Thromb Hemost

104

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Impaired blood flow due to abnormal rheologic characteristics results in a multiplicity of clinical manifestations, collectively termed the hyperviscosity syndrome. A basic knowledge of the principles of rheology is important in the understanding of its pathophysiology, especially the relationship between viscosity and flow conditions. The flow characteristics in different types of blood vessels are also determinants in the location of the clinical manifestation. The syndrome can occur in a wide variety of diseases and is best grouped according to the causative element or elements in blood. Abnormalities in the cellular components of blood can occur in the quantity and the quality of erythrocytes, leukocytes, and platelets. Abnormal plasma components can also be in both the quantity and quality of the plasma proteins. Clinical manifestations are the result of vascular occlusion, especially in the microcirculation. The altered rheologic characteristics of either the cellular or the protein component may be temperature dependent, being abnormal only at temperatures below 37 degrees C, so that only the cooler parts of the body are affected. The management of these conditions should be primarily directed at the removal of the abnormal component. At the same time, it should be accompanied by measures that can control the production of the causative element.

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Biology, Clinical Patterns, and Treatment of Multiple Myeloma and Related Plasma–Cell Dyscrasias

Cited by 10 publications

References 370 publications

Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta

Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta

Late occurrence of IgD myeloma in plasmacytoma of nasal cavity, cervical lymph node and larynx

The Hyperviscosity Syndromes

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