Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelosuppression and immunosuppression are terms that often are used interchangeably, yet they have very different meanings. Myelosuppression, which is caused by many types of cancer treatments (e.g., chemotherapy, radiation therapy), occurs when the body's population of blood cells is lowered. In contrast, immunosuppression occurs when the body's immune function is compromised. Diseases of either the B or T lymphocytes (e.g., lymphoma, multiple myeloma, CLL) alter the normal functioning of the lymphocytes, rendering them unable to mount an immune response. With CLL, B lymphocytes are unable to mature into immunoglobulin-producing plasma cells (delGiglio et al., 1993). Multiple myeloma occurs when the plasma cells become malignant (Mansen et al., 1997). Knowledge of the basic principles of immunology assists nurses in understanding the complexities of the immune system and the effects of common cancer treatments. Patients with CLL require astute assessment of infectious symptoms, comprehensive nursing care and symptom management, and education about the disease and its effects. Hays and McCartney (1998) also noted that the challenges of caring for patients with CLL include patient management in the outpatient setting, quality-of-life issues, and ongoing support because of the chronicity of the disease.
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PMID:Chronic lymphocytic leukemia and its impact on the immune system. 1111 55

Thalidomide has recently been shown to have significant activity in refractory multiple myeloma (MM). A follow-up of the original phase II trial, expanded to 169 patients, shows 2-year survival of 60%; patients receiving > or =42 g over 3 months had a higher response rate and superior survival than those receiving lower doses. The addition of thalidomide to dexamethasone and chemotherapy for the management of post-transplant relapses results in higher response rates. The early results of the Total Therapy II trial for newly diagnosed MM patients show an unprecedented complete remission (CR) and near-CR rate of 69% after two melphalan-based transplants (whether or not receiving thalidomide). In addition, available clinical trial information involving at least 20 patients confirms that thalidomide is active in one third of patients in single-agent trials for refractory disease, with response rates increasing to 50% to 60% in combination with dexamethasone and to as high as 80% in combination with dexamethasone and chemotherapy. When applied as primary therapy in smoldering myeloma, one third of patients experienced 50% paraprotein reduction (PPR); in combination with dexamethasone pulsing, 70% to 80% of symptomatic patients responded. Thus, thalidomide is a major new tool in the treatment armamentarium of MM. The virtual lack of myelosuppression makes it an ideal agent for combination with cytotoxic chemotherapy. Newer, more potent, and less toxic derivatives of thalidomide are being evaluated.
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PMID:Thalidomide in the management of multiple myeloma. 1148 13

We investigated the graft-versus-myeloma effect (GVM) after allogeneic bone marrow transplantation (allo-BMT). Three patients with refractory multiple myeloma (MM) underwent related allo-BMT. Two of the patients showed disappearance of serum M protein 4 and 5 months after transplantation, respectively. One of them has remained in complete remission for more than 22 months after allo-BMT, with accompanying chronic GVHD. Two patients with relapse and disease progression after allo-BMT underwent donor lymphocyte infusion (DLI). Although one patient did not respond to DLI, the other developed acute GVHD after 4 weeks and achieved a 75% reduction in serum M protein. DLI did not produce severe acute GVHD or myelosuppression. These findings suggest the presence of a GVM effect. DLI may be an effective therapy for patients with MM who have relapsed after allo-BMT. Furthermore, non-myeloablative stem cell transplantation (mini-transplantation) for refractory MM should be investigated further as a potentially curative option.
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PMID:[Allogeneic bone marrow transplantation for refractory multiple myeloma: presence of a graft-versus-myeloma effect]. 1150 27

Melphalan was the first described treatment for patients with multiple myeloma in the 1960s and is still being used in clinical practice. However, the use of melphalan in combination with prednisone resulted in a median survival of only 2-3 years. Therefore, the dose of melphalan has been intensified since then (140-200 mg/m(2)). In order to diminish treatment-related morbidity and mortality due to severe myelosuppression induced by these regimens, high-dose melphalan is currently supported with autologous stem cells. Indications for high-dose therapy and the role of further intensification by performing second or allogeneic transplantations are discussed. Furthermore, new therapeutic modalities, such as inhibitors of angiogenesis, also showing direct antiproliferative, cytokine-related and immunomodulatory effects on plasma cells (thalidomide and its newer derivatives), inhibitors of the transcription factor NF-kappa B (proteasome inhibitors) and immunotherapy are described.
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PMID:Treatment of myeloma: recent developments. 1198 79

Thalidomide (Thal) can overcome drug resistance in multiple myeloma (MM) but is associated with somnolence, constipation, and neuropathy. In previous in vitro studies, we have shown that the potent immunomodulatory derivative of thalidomide (IMiD) CC-5013 induces apoptosis or growth arrest even in resistant MM cell lines and patient cells, decreases binding of MM cells to bone marrow stromal cells (BMSCs), inhibits the production in the BM milieu of cytokines (interleukin-6 [IL-6], vascular endothelial growth factor [VEGF], tumor necrosis factor-alpha [TNF-alpha]) mediating growth and survival of MM cells, blocks angiogenesis, and stimulates host anti-MM natural killer (NK) cell immunity. Moreover, CC-5013 also inhibits tumor growth, decreases angiogenesis, and prolongs host survival in a human plasmacytoma mouse model. In the present study, we carried out a phase 1 CC-5013 dose-escalation (5 mg/d, 10 mg/d, 25 mg/d, and 50 mg/d) study in 27 patients (median age 57 years; range, 40-71 years) with relapsed and refractory relapsed MM. They received a median of 3 prior regimens (range, 2-6 regimens), including autologous stem cell transplantation and Thal in 15 and 16 patients, respectively. In 24 evaluable patients, no dose-limiting toxicity (DLT) was observed in patients treated at any dose level within the first 28 days; however, grade 3 myelosuppression developed after day 28 in all 13 patients treated with 50 mg/d CC-5013. In 12 patients, dose reduction to 25 mg/d was well tolerated and therefore considered the maximal tolerated dose (MTD). Importantly, no significant somnolence, constipation, or neuropathy has been seen in any cohort. Best responses of at least 25% reduction in paraprotein occurred in 17 (71%) of 24 patients (90% confidence interval [CI], 52%-85%), including 11 (46%) patients who had received prior Thal. Stable disease (less than 25% reduction in paraprotein) was observed in an additional 2 (8%) patients. Therefore, 17 (71%) of 24 patients (90% CI, 52%-85%) demonstrated benefit from treatment. Our study therefore provides the basis for the evaluation of CC-5013, either alone or in combination, to treat patients with MM at earlier stages of disease.
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PMID:Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. 1238

Gallium nitrate, the nitrate salt of the "near-metal" element gallium, is highly effective in the treatment of cancer-related hypercalcemia. Unlike bisphosphonates, gallium nitrate is effective in both parathyroid hormone-related protein-mediated and non-parathyroid hormone-related protein-mediated hypercalcemia. Gallium nitrate's effects on bone are clearly different from those of bisphosphonates. Gallium nitrate enhances calcium and phosphate content of bone and has direct, noncytotoxic effects on osteoclasts at markedly lower doses than those used for the treatment of cancer-related hypercalcemia. The drug may have clinical application in a variety of disorders associated with accelerated bone loss, including multiple myeloma. Gallium nitrate was originally evaluated as an antitumor agent. Its antitumor activity occurs at somewhat higher doses than those used in the treatment of cancer-related hypercalcemia. Gallium nitrate has substantial single-agent activity in the treatment of advanced lymphoma, particularly diffuse large cell lymphoma, small lymphocytic lymphoma, and follicular lymphoma. Because of its profile, including a different mechanism of action and minimal myelosuppression, the drug merits further evaluation in the treatment of advanced lymphoma. Gallium nitrate also has activity in advanced bladder cancer and may be useful in patients with metastatic or unresectable disease failing first-line chemotherapy regimens. Gallium nitrate exhibits a range of dose-dependent pharmacologic actions that provide a basis for its therapeutic potential in a variety of diseases and warrants further investigational evaluation as an antiresorptive and antitumor agent.
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PMID:Gallium nitrate revisited. 1277 53

Thalidomide is an antiangiogenic drug, but its mechanism of action is not well known and demands further studies. The recent literature suggests that thalidomide is an effective drug in multiple myeloma patients. The objective of the study was to estimate the efficacy of thalidomide monotherapy in the treatment of refractory and relapsed cases of multiple myeloma. We treated with thalidomide 17 patients (12 males, 5 females), average age 51 (range 42-73 years), mean time since diagnosis to the start of thalidomide treatment was 24 months (range 5-48). All patients revealed the features of progressive disease. The mean number of prior chemotherapy schemes was 2. Three out of 17 patients received high dose chemotherapy followed by autologous stem cell transplantation. Thalidomide was administered as monotherapy at a dose of 200 mg (n = 8), 300 mg (n = 1) and 400 mg (n = 8). The mean time of drug intake was 3 months (1-12). The criteria of clinical response were decline of paraprotein at least 25%, 50% and 75% in comparison to value before the treatment. In 5 cases (33%) 25% reduction of paraprotein was observed, 1 patient achieved 50% decline. In the responder group a tendency to decrease marrow plasmocytosis, total serum protein, beta M-2 and LDH was noticed. The good tolerance of the drug, especially in lower doses, and lack of myelosuppression effect allows to expect, that the combination of thalidomide with other cytostatic drugs will improve the efficacy in patients with refractory or relapsed myeloma.
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PMID:[Preliminary results of monotherapy with thalidomide in recurrent and treatment resistant cases of multiple myeloma]. 1452 79

Allogeneic stem cell transplantation has a well-defined indication in the treatment of hematological malignancies. The beneficial immune effect of allogeneic marrow transplantation has long been known, but only recently have methods been developed to separate the graft-versus-leukemia (GVL) effect from graft-versus-host disease (GVHD). Animal experiments have shown that lymphocytes from the marrow donor can be transfused without causing severe GVHD if stable chimerism and tolerance is established. First clinical studies have been preformed in patients with recurrent chronic myelogenous leukemia. In these patients complete molecular remissions were induced that persist without further maintenance treatment. These results have been confirmed in larger multicenter studies in Europe and the USA. The best results were obtained in chronic myelogenous leukemia (CML); repeated successes have been reported in relapsing acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma (MMY), and rare responses were reported for acute lymphoid leukemia. Contrary to animal experiments GVHD has been observed in human patients although to a lesser extent than expected in transplants not given immunosuppression. Secondly myelosuppression has been observed in patients treated with relapsing CML. In CML the incidence of GVHD could be reduced by depleting CD8+ T cells from the donor lymphocyte concentrate. Alternatively only small numbers of T lymphocytes can be transfused and in the case of failing responses, the numbers of donor lymphocytes may be increased. Results in recurrent AML have been improved by the use of low-dose cytosine arabinoside, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor mobilized blood cells as compared to lymphocytes only. In MMY the response rate is higher than in AML, but the remissions are of limited duration in most patients. Several protocols have been designed to include preemptive donor lymphocyte transfusion in patients with a high relapse risk after transplantation. Problems remain to avoid chronic GVHD and to circumvent the immune escape mechanisms of leukemia.
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PMID:Adoptive immunotherapy in chimeras with donor lymphocytes. 1458 71

The skeleton is the third most common site for cancer to spread to after the liver and lungs. Malignancies that can cause destruction of skeletal bones include multiple myeloma and metastatic disease of the breast, prostate, and lung. Bone metastases are problematic for patients with cancer because accelerated bone breakdown occurs with many associated complications. One or more of the following problems may occur: pain, hypercalcemia, pathologic fractures, myelosuppression, and spinal cord compression with subsequent progressive immobility. Quality of life is affected negatively, and associated feelings of fear, grief, anger, despair, anxiety, and depression can occur. Management of malignancies of the bone involves a multimodal approach. Therapies include analgesia, hormone therapy, chemotherapy, surgery, radiation therapy, and the use of bisphosphonates. Nurses can be instrumental in promoting positive outcomes for patients with bone metastases.
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PMID:Advances in the treatment of bone metastases. 1470 79

An active assessment of the host capacity to prevent infection during myelosuppression should be beneficial in patients receiving high-dose chemotherapy. A single dose of granulocyte colony-stimulating factor (G-CSF) (5 microg/kg) was given to 57 patients with multiple myeloma early after the completion of 85 high-dose chemotherapy (melphalan 200 mg/m2) courses. This provoked a highly variable white blood cell (WBC) peak after 12 to 14 hours. The median WBC count was 21,000/microL (range, 6400-60,600/microL) after a first high-dose therapy (n = 50) and 13,500/microL (range, 4700-24,800/microL) after a second high-dose therapy (n = 35). The responsiveness to single G-CSF was associated with the risk of infection during subsequent cytopenia (P =.003). This association was significant after adjustment for neutropenia duration. Notably, the result of testing G-CSF responsiveness was opportunely available before the onset of leukopenia, and G-CSF responsiveness was more informative than neutropenia duration regarding the risk of infection. Furthermore, there was an association between the responsiveness to G-CSF and stem cell engraftment (P <.005), which remained significant after adjustment for the number of transplanted CD34+ cells. Our results show for the first time that G-CSF potentially could be used for an early in vivo assessment of defense to infection in recipients of high-dose chemotherapy.
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PMID:Responsiveness to G-CSF before leukopenia predicts defense to infection in high-dose chemotherapy recipients. 1520 65


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