Biomedical subjects

Donna M Weber

Publications and source records attributed to Donna M Weber.

9 recordsLinked to original sources

PubMed2006

Nuclear BCL-10 expression is common in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and does not correlate with p65 NF-kappaB activation.

B-cell lymphoma 10 (BCL-10) is expressed in the cytoplasm of normal germinal center and marginal zone B-cells and is involved in lymphocyte development and activation. Aberrant nuclear expression of BCL-10 occurs in a subset of extranodal marginal zone B-cell lymphomas (MALT lymphomas), primarily those with the t(1;14)(p22;q32) or t(11;18)(q21;q21). Little is known about BCL-10 expression in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). We assessed for BCL-10 in 51 bone marrow (BM) specimens involved by LPL/WM using immunohistochemical methods. All patients had monoclonal IgM in serum. Extent of BM involvement was assessed using PAX-5/BSAP and CD20 immunostains and the pattern and percentage of B-cells positive for BCL-10 was determined. The p65 subunit of nuclear factor-kappa B (NF-kappaB), a molecule downstream of BCL-10, was also assessed immunohistochemically. Nuclear BCL-10 staining was present in 28/51 (55%) specimens. BCL-10 expression correlated with greater extent of BM involvement (P=0.001), but did not correlate with serum IgM paraprotein levels, type of immunoglobulin light chain, or clinical variables. Nuclear expression of the p65 subunit of NF-kappaB was detected in 17/50 (34%) specimens, suggesting that NF-kappaB is active in a subset of LPL/WM. p65 NF-kappaB activation did not correlate with nuclear BCL-10 immunostaining. Cytogenetic analysis in 29 cases showed no evidence of the t(1;14) or t(11;18). These results indicate that nuclear BCL-10 expression is common in LPL/WM and does not correlate with MALT lymphoma-associated translocations or p65 NF-kappaB nuclear staining.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Scleromyxedema: role of high-dose melphalan with autologous stem cell transplantation.

Scleromyxedema, the most severe manifestation of the spectrum of lichen myxedematosus, is characterized by cutaneous mucinosis, extracutaneous manifestations, and a monoclonal gammopathy. Seven of 8 patients evaluated at our center were treated with high-dose melphalan (180 mg/m(2) intravenously) and autologous peripheral blood stem cell transplantation, with marked improvement of gastrointestinal, central nervous system, pulmonary manifestations, and Karnofsky performance status. Five patients obtained a cutaneous complete remission and 2 patients had partial remissions. Three patients with slight progression in the skin at 12, 8, and 4 months after treatment received a second cycle of high-dose melphalan and had further symptomatic improvement. The lichen myxedematosus-scleromyxedema spectrum appears to be a continuum that requires the presence of a serum paraprotein and differs in severity of skin lesions, extracutaneous manifestations, and performance status. High-dose melphalan followed by autologous transplantation appears effective for improving the symptoms and systemic manifestations of scleromyxedema.

Adult↗

PubMed2005

Thalidomide-dexamethasone as primary therapy for advanced multiple myeloma.

The value of thalidomide-dexamethasone was assessed in 26 consecutive, previously untreated patients with multiple myeloma of high tumor mass. All showed Hgb < 8.5 g/dL, serum calcium > 11.5 mg/dL, or both. The response rate was 73%, frequency of early death < 3 months was 5%, projected median survival was 30 months, and projected median remission time was 25 months. There were no occurrences of grade 3 or 4 neutropenia or thrombocytopenia, so that serious infection occurred in only 12% of patients. Thalidomide-dexamethasone was useful for these patients with advanced disease because of the high response rate and acceptable survival, with a low frequency of serious complications.

Adult↗

PubMed2005

Solitary bone and extramedullary plasmacytoma.

Less than 5% of patients with a plasma cell dyscrasia present with a single bone (SBP) or extramedullary plasmacytoma (EMP) without evidence of systemic disease (normocalcemia, absence of anemia, preservation of uninvolved immunoglobulins, or renal disease attributable to myeloma). Diagnosis requires biopsy confirmation of a monoclonal plasma cell infiltrate from a single site. The treatment of choice for both entities is radiotherapy given with curative intent (> 4000 cGy) resulting in long term disease-free survival in approximately 30% of patients with SBP and 65% of patients with EMP.

Biomarkers↗

PubMed2004

Treatment of Waldenstrom's macroglobulinemia with rituximab: prognostic factors for response and progression.

Recent data have suggested that rituximab is an active agent for the treatment of Waldenstrom's macroglobulinemia (WM). However, the patients that are more likely to benefit have not been clearly defined. In order to address this question we evaluated 52 patients who were treated with single-agent rituximab in the context of prospective studies. Several clinical and laboratory variables were assessed for their correlation with response and time to progression. Twenty-three (44%) patients achieved a partial response after treatment with rituximab. Previously untreated and pretreated patients had the same probability for response. Higher response rates were noted in patients with serum monoclonal protein < 40 g/l, with serum albumin > or = 35 g/l and with kappa light chain. The median time to progression for all patients was 13.8 months. A multivariate analysis indicated that elevated serum monoclonal protein levels and low serum albumin were the dominant variables associated with shorter progression. Presence of two, one or none of these adverse prognostic factors was associated with time to progression of 3.6 months, 11 months and more than 40 months, respectively. We conclude that rituximab is an effective treatment modality for patients with WM. Patients with both low levels of monoclonal protein and normal albumin are the best candidates for treatment with standard dose rituximab.

Aged↗

PubMed2003

Use of plasma DNA in detection of loss of heterozygosity in patients with multiple myeloma.

BACKGROUND: Deletions or structural abnormalities in chromosomes 11 and 13 have been shown to be important in predicting clinical behavior in patients with multiple myeloma (MM). However, cytogenetic analysis in MM is frequently difficult because of poor yield of informative metaphases and the disease is frequently patchy, which complicates fluorescent in situ hybridization studies. OBJECTIVES: The purpose of this study was to explore the potential of using peripheral plasma DNA for the detection of loss of heterozygosity (LOH) in chromosomes 11 and 13 in patients with MM. METHODS: Peripheral blood (PB) plasma of 81 patients with MM, was used as a source of DNA for the detection of LOH at chromosomes 13q14 (D13S319 and D13AFMaw301wb5), and 11q21 (D11S2179) using polymerase chain reaction. RESULTS: Only 62 of the studied patients were informative for the two 13q microsatellite markers and 16 (26%) of these patients showed LOH. Only seven (11%) of 61 patients with informative D11S2179 microsatellite maker showed LOH. Purified plasma cells (PCs) from six bone marrow (BM) samples using anti-CD138-coated magnetic beads showed identical results to those detected in DNA isolated from PB plasma. Three patients with LOH underwent autologous BM transplantation, and two of three reverted to a normal state (no LOH) after transplantation. Seven of the patients with 13q LOH in PB plasma had <10% PCs (PCs) in their BM at the time of testing. CONCLUSION: PB plasma appears to be enriched by tumor-specific DNA and can be used to detect chromosomal abnormalities in patients with MM. Further studies are needed to establish the clinical relevance of this approach in comparison with other techniques.

Adult↗

PubMed2003

2-Chlorodeoxyadenosine alone and in combination for previously untreated Waldenstrom's macroglobulinemia.

Treatment for Waldenstrom's macroglobulinemia (WM) has usually been reserved for symptomatic patients and has included alkylating agent-steroid combinations and, more recently, nucleoside analogues. We now describe our experience with 2-chlorodeoxyadenosine (2-CdA) alone and in combination at our center. We treated 90 consecutive, previously untreated patients with symptomatic WM using either 2-CdA alone or in combination with other agents including prednisone (pred), cyclophosphamide (Cy), and rituximab (Rit) as follows: January 1991 to December 1992- 2-CdA 0.1 mg/kg by continuous infusion (CI) over 24 hours for days (16 patients); December 1992 to December 1995-2-CdA 0.1 mg/kg CI over 24 hours for 7 days plus pred 60 mg/m(2) orally daily for 7 days (20 patients); July 1996 to March 1998-2-CdA 1.5 mg/m(2) by subcutaneous injection (SC) every 8 hours for 7 days plus Cy 40 mg/m(2) orally twice daily for 7 days (37 patients); August 1999 to December 2001-2-CdA 1.5 mg/m(2) SC every 8 hours for 7 days plus Cy 40 mg/m(2) orally twice daily for 7 days plus Rit 375 mg/m(2) by intravenous infusion (IV) weekly for 4 weeks (17 patients). For nearly all patients, a second course was repeated after at least 6 weeks. Responding patients were monitored without further treatment until relapse. Overall response (complete [CR] + partial response [PR]) was 94% for 2-CdA alone, 60% for 2-CdA/pred, 84% for 2-CdA/Cy, and 94% for 2-CdA/Cy/Rit. Median overall survival is 73 months for 2-CdA, 41 months for 2-CdA/pred, and has not been reached for 2-CdA/Cy or 2-CdA/Cy/Rit. Cause-specific survival for 2-CdA/pred is 78 months and has not been reached for all other programs. The only poor prognostic factor for cause-specific survival was hemoglobin < 9 g/dL. 2-CdA regimens provide excellent response rates and improve cause-specific survival, with minimal treatment and little toxicity. These observations support the potential role of 2-CdA regimens as the treatment of choice for previously untreated WM.

Aged↗

PubMed2003

Strategies in treating newly diagnosed or untreated multiple myeloma patients. From the Multiple Myeloma Research Foundation.

Treatment regimens for multiple myeloma are evolving because of new advances in both pharmacotherapy and transplantation strategies. The Multiple Myeloma Research Foundation (MMRF) has gathered the top thought leaders in myeloma research to prepare an engaging, interactive series of case studies in multiple myeloma, which are available online at www.multiplemyeloma.org and will be published on a regular basis in ONCOLOGY.

Analgesics, Opioid↗

PubMed2002

Newly diagnosed multiple myeloma.

Melphalan combined with prednisone (MP) has been accepted as the standard therapy for previously untreated multiple myeloma (MM) because most studies demonstrate only a modest survival benefit of combination chemotherapy regimens when compared with MP. There have been modest gains with more intensive myeloablative regimens in combination with blood stem cell support, particularly for patients with early primary refractory disease who subsequently achieve partial remission, and for the approximately 25% to 35% of patients achieving complete remission. To preserve the ability to adequately collect stem cells, the use of alkylating agents, such as melphalan, should be limited in the previously untreated patient with myeloma (including those older than 65 years of age) who is a candidate for myeloablative therapy. Pulse dexamethasone-containing regimens provide rapid responses and may be considered the first regimens of choice. Although vincristine/doxorubicin/dexamethasone (VAD) produces responses in approximately 50% to 70% of patients with previously untreated multiple myeloma, use early in the disease has not improved survival. Outside of a specific study protocol, this regimen may be best reserved for patients with refractory (particularly relapsing) disease. Notable exceptions include patients with renal failure or plasma cell leukemia in whom the rapid responses provided by VAD may avoid potentially permanent, serious complications. Recently, new agents with novel mechanisms of action (ie, thalidomide, immunomodulatory drugs, proteosome inhibitors) have demonstrated activity in resistant myeloma. Because these agents are likely to show activity alone or in combination, newly diagnosed patients and previously untreated patients should be considered for clinical trials. Thalidomide/dexamethasone has already produced response rates of 65% to 75% in previously untreated patients. Its ease of administration along with stem cell preservation are likely to make this, followed by myeloablative therapy with stem cell support, the treatment of choice for untreated myeloma as confirmatory studies are completed.

Antineoplastic Agents↗