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)

The objective of our study was to delineate clinical features and specific diagnostic and therapeutic implications of spinal epidural metastasis (SEM) occurring as the initial manifestation of malignancy (IMM)-a less common event than SEM in the setting of previously established malignancy (PEM). We performed a retrospective review of the clinical histories of 337 patients seen at Mayo Clinic with a radiographically verified diagnosis of SEM between January 1, 1985, and December 31, 1993. Twenty percent of all cases of SEM occurred as SEM-IMM. Carcinoma of the lung, cancer of unknown primary site, multiple myeloma, and non-Hodgkin's lymphoma were disproportionately represented in SEM-IMM, together accounting for 78% of SEM-IMM patients and only 26% of SEM-PEM patients. Inversely, breast and prostate carcinoma contributed only 12% of SEM-IMM patients but 51% of SEM-PEM patients. Only 27% of patients with SEM-IMM had nonspecific symptoms suggesting malignancy, and in only 24% did the history or physical examination suggest the primary site of malignancy. Percutaneous needle biopsy of the vertebral lesion was diagnostic of malignancy in 18 of 19 patients (95%), and no complications ensued. Fifteen patients underwent diagnostic laminectomy with biopsy, and one had a fatal complication. Survival after the diagnosis of SEM did not differ between patients with SEM-IMM and those with SEM-PEM; the median survival was 6.6 months. SEM not uncommonly occurs as the presentation of malignancy, and often it produces the only symptoms or signs of malignancy. The great majority of neoplasms presenting with SEM are carcinomas of the lung, unknown primary lesions, and hematologic malignancies. Computed tomography-guided needle biopsy is a safe, efficacious means of diagnosing malignancy, allowing for rational diagnostic workup and staging. In most patients it obviates a diagnostic spinal surgical procedure.
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PMID:Spinal epidural metastasis as the initial manifestation of malignancy: clinical features and diagnostic approach. 927 May 76

The major limitation to the use of immunotoxins in the clinic is the toxicity associated with the toxin moiety. BD1-G28-5 single-chain Fv (sFv) is a single-chain immunotoxin targeted to human CD40 and consists of bryodin 1 (BD1), a plant ribosome-inactivating protein that is 20-30-fold less toxic in animals than commonly used toxins, fused to the sFv region of the anti-CD40 monoclonal antibody G28-5. This immunotoxin was expressed in Escherichia coli and purified from refolded inclusion bodies. BD1-G28-5 sFv retained the full protein synthesis inhibition activity of recombinant BD1 and specifically bound to CD40 with a binding affinity, kd, of 1.5 nM, within 10-fold of the bivalent parental monoclonal antibody. BD1-G28-5 sFv was potently cytotoxic against CD40-expressing B lineage non-Hodgkin's lymphoma and multiple myeloma cell lines, with EC50 values in the ng/ml range, but not against a CD40-negative T cell line. Interestingly, BD1-G28-5 sFv was not cytotoxic against CD40-expressing carcinoma cell lines that were sensitive to a BD1-based immunotoxin conjugate targeted to the Ley carbohydrate antigen. These data represent the first report indicating that BD1 can be used in the construction of potent single-chain immunotoxins. Additionally, although BD1-G28-5 sFv effectively killed CD40-expressing hematologic malignancies, its lack of activity against CD40-expressing carcinomas suggests that CD40-mediated trafficking of BD1 differs in the two cancer types.
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PMID:Construction, expression, and characterization of BD1-G28-5 sFv, a single-chain anti-CD40 immunotoxin containing the ribosome-inactivating protein bryodin 1. 930 66

The development of multidrug resistance (MDR) is a major obstacle to improving treatment outcomes in multiple myeloma. Recent studies have indicated that several specific mechanisms of MDR may be involved in clinically refractory multiple myeloma patients, such as expression of P-glycoprotein (P-gp), expression of the lung-resistance protein (LRP) and suppression of apoptosis via expression of Bcl-2. The emergence of these mechanisms of MDR in multiple myeloma is enhanced by exposure to chemotherapeutic agents. Recently, clinical reversal of MDR by noncytotoxic P-gp modulators such as verapamil, cyclosporin A (CsA), and PSC 833 was explored in acute leukemia and multiple myeloma. Preliminary results from clinical phase I/II trials indicate that reversal of MDR via modulation of P-gp is possible and that coadministration of these MDR modulators with chemotherapeutic agents alters the plasma pharmacokinetics of chemotherapeutic agents. Phase II and III clinical trials investigating the efficacy of these and other agents in the reversal of MDR in hematologic malignancies are ongoing.
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PMID:Drug resistance in multiple myeloma. 940 59

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.
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PMID:Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States). 948 66

Dendritic cells (DC) are antigen-presenting cells with the potential to be a powerful adjuvant in the immunotherapy of haematological malignancy, including myeloma. Recently, human herpesvirus 8 (HHV-8) infection of dendritic cells in the long-term bone marrow stromal cultures of patients with myeloma has been reported. This finding is of great potential importance regarding oncogenesis in myeloma in addition to having significant implications for the use of DC in the immunotherapy of this disease. Therefore DC generated from mobilized blood mononuclear cells (MO-DC) and purified CD34+ cells (CD34-DC) of myeloma patients were examined for the presence of HHV-8 using a sensitive PCR technique. HHV-8 was not demonstrated in MO-DC or CD34-DC and we conclude that these cells remain a suitable vehicle for investigation in the immunotherapy of myeloma.
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PMID:Dendritic cells cultured from mononuclear cells and CD34 cells in myeloma do not harbour human herpesvirus 8. 953 51

Donor lymphocyte infusions (DLI) can induce remissions in patients who have relapsed after allogeneic bone marrow transplantation (BMT). However, DLI frequently also result in significant acute and/or chronic graft-versus-host disease (GVHD). Several clinical and experimental lines of evidence have suggested that CD8(+) T cells play a critical role in the pathogenesis of GVHD. To develop methods to reduce the incidence of GVHD associated with DLI, we administered defined numbers of CD4(+) donor T cells after ex vivo depletion of CD8(+) lymphocytes to 40 patients with relapsed hematologic malignancies after allogeneic BMT. Cohorts of patients received 0.3, 1.0, or 1.5 x 10(8) CD4(+) cells/kg. Overall, 12 of 38 patients (32%) evaluable for toxicity developed acute or chronic GVHD. However, 6 of 27 patients (22%) receiving 0.3 x 10(8) CD4 cells/kg developed GVHD compared with 6 of 11 patients (55%) who received >/=1.0 x 10(8) CD4 cells/kg (P = .07). Treatment-related mortality was low (3%), with 1 death related to infection in the setting of immunosuppression for GVHD. Disease responses after CD4(+) DLI were documented in 15 of 19 patients (79%) with early-phase chronic myelogenous leukemia (CML) relapse, 5 of 6 patients (83%) with relapsed multiple myeloma, and 1 patient with myelodysplasia. For patients with early-phase CML relapse, the Kaplan-Meier probability of achieving complete cytogenetic remission was 87% and the probability of complete molecular response was 78% at 1 year after DLI. The median time to complete cytogenetic response and molecular response in patients with CML was 13 weeks (range, 9 to 30 weeks) and 34 weeks (range, 10 to 56 weeks), respectively. The median time to response in patients with multiple myeloma was 26 weeks (range, 15 to 62 weeks). All patients in this trial who developed GVHD demonstrated tumor regression, but the presence of GVHD was not required for patients to achieve a response, because 48% of responding patients never developed evidence of GVHD. Two patients with CML who did not respond at dose level 1 subsequently achieved complete cytogenetic remission after a second infusion of CD8-depleted cells at dose level 2. In patients with evidence of mixed hematopoietic chimerism who achieved a complete remission after DLI, cytogenetic analysis of marrow cells also demonstrated conversion to complete donor hematopoiesis in all evaluable patients. These studies suggest that relatively low numbers of CD8-depleted donor lymphocytes are effective in inducing complete remissions in patients with stable-phase CML and multiple myeloma who have relapsed after allogeneic BMT. Because of the relatively low risk of toxicity associated with the infusion of defined numbers of CD4(+) donor cells, further studies can be undertaken in the setting of persistent minimal residual disease to prevent relapse after allogeneic BMT.
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PMID:Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. 957 3

Systemic sclerosis is uncommonly associated with hematologic malignancies. We report the case of a patient who had chronic myelogenous leukemia 3 years after the CREST variant of systemic sclerosis was diagnosed. She also later had porphyria cutanea tarda. The majority of patients who had hematologic malignancies after the diagnosis of systemic sclerosis proved to have either multiple myeloma or chronic lymphocytic leukemia. Hematologic malignancies may be found in patients with systemic sclerosis (either limited or diffuse).
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PMID:Chronic myelogenous leukemia and porphyria cutanea tarda in a patient with limited systemic sclerosis. 959 64

We evaluated the usefulness of fluorescence in situ hybridization (FISH) using different-colored commercial RB1 and 13qter DNA probes to identify RB1 deletions in interphase nuclei of bone marrow from 24 patients with agnogenic myeloid metaplasia (AMM), 20 patients with multiple myeloma (MM), 21 patients with other hematologic malignancies, and 25 normal bone marrow transplant (BMT) donors. Based on the 25 normal BMT donors, the upper boundary for the normal percentage of nuclei with one RB1 signal was 6.5%. Based on eight specimens known to have a deletion of 13q14 by cytogenetic studies, the lower limit of abnormal for the percentage of nuclei with one RB1 signal was 12.5%. More than 12.5% of nuclei had a single RB1 signal in 7/24 (29%) patients with AMM and 3/20 (15%) patients with MM. None of the 21 patients with hematologic malignancies other than AMM or MM had more than 12.5% nuclei with loss of RB1. The results of this study suggest that FISH with RB1 probes is useful to detect loss of RB1 in interphase nuclei from patients with hematologic disorders who have chromosome abnormalities involving 13q14. Thus, FISH with probes for RB1 is efficacious to investigate the pathogenesis of RB1 in malignant neoplasms and is a useful adjunct to conventional cytogenetic studies in clinical practice when abnormalities of 13q14 are involved.
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PMID:Detection of RB1 deletions by fluorescence in situ hybridization in malignant hematologic disorders. 961 9

Anemia is a frequent complication in hematologic malignancies. In advanced stages of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and myeloma, anemia usually develops in parallel with marrow involvement. However, anemia may occur in the absence of overt infiltration of bone marrow by malignant cells. When all other causes of anemia (such as chronic bleeding, vitamin deficiency, hemolysis, and pure red blood cell aplasia) are eliminated, anemia can be related to "anemia of chronic disorders." Myelodysplastic syndromes are characterized by cytopenias. Anemia is very frequent, and nearly 90% of patients present with anemia during the evolution of the disease. In this disorder, erythroid progenitors are defective for their proliferation and maturation, as shown by in vitro culture techniques. Moreover, these patients often have a high endogenous serum erythropoietin level. The rationale for treating these patients with epoetin alfa is the possibility of overcoming the defective proliferation by pharmacologic doses of epoetin alfa. The response rate was rather low with epoetin alfa alone. Combinations with earlier-acting cytokines, such as recombinant human granulocyte colony-stimulating factor, have been tested in an attempt to improve response rates.
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PMID:Update on the role of epoetin alfa in hematologic malignancies and myelodysplastic syndromes. 967 24

Transplantation of mobilized peripheral blood stem cells (PBSC) for rescue of bone marrow function after high-dose chemo-/radiotherapy is widely used in hematologic malignancies and solid tumors. Mobilization of stem cells to the peripheral blood can be achieved by cytokine treatment of the patients. The main advantage of autologous PBSC transplantation over bone marrow transplantation is the faster recovery of neutrophil and platelet counts. The threshold number of PBSC required for adequate rescue of bone marrow is thought to be about 2 x 10(6) CD34+ cells/kg, if the stem cells are collected by leukapheresis and subsequently cryopreserved. We show that this critical number could be further reduced to as few as 0.2 x 10(6) cells/kg. In 30 patients with multiple myeloma and 25 patients with bad risk lymphoma 1 liter of granulocyte colony-stimulating factor (G-CSF)-mobilized unprocessed whole blood (stored at 4 degrees C for 1-3 days) was used for transplantation. Compared to a historical control group, a significant reduction in the duration of neutropenia, thrombocytopenia and the length of hospital stay was documented. Furthermore, the effect of stem cell support was reflected by a lower need for platelet and red cell transfusions and a reduced antibiotic use. Considering the data as a whole, a cost saving of about 50% was achieved. To date, this easy to perform method of transplantation is only feasible following high-dose therapies that are completed within 72 h, since longer storage of unprocessed blood is accompanied by a substantial loss of progenitor cell function. Ongoing investigations include attempts to prolong storage times for whole blood.
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PMID:New strategies in hematopoietic stem cell transplantation: G-CSF-mobilized unprocessed whole blood. 968 78


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