Biomedical subjects

Donna Weber

Publications and source records attributed to Donna Weber.

13 recordsLinked to original sources

PubMed2004

Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma.

BACKGROUND: High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) as part of the initial treatment regimen improves progression-free survival (PFS) and overall survival (OS) for patients with multiple myeloma. The optimal preparative regimen for patients with multiple myeloma has yet to be defined. In the current study, the authors compared the outcomes associated with high-dose melphalan (HDM) and a more intensive regimen of thiotepa, busulfan, and cyclophosphamide (TBC) in patients with multiple myeloma. METHODS: One hundred eighty-six patients with newly diagnosed multiple myeloma (median age, 51 years) received HDC with ASCT for consolidation of first remission (n = 108) or for treatment of primary refractory disease (n = 78). Seventy patients had a large tumor mass at the time of diagnosis. The preparative regimen consisted of TBC for 97 patients and HDM for 89 patients. Patients in the TBC group were younger and had more advanced disease stage at diagnosis and at the time of ASCT compared with patients in the HDM group. RESULTS: The response rates (complete response [CR] and partial response [PR]) were similar in the TBC group (overall response rate, 66%; CR rate, 17%; PR rate, 49%) and the HDM group (overall response rate, 69%; CR rate, 28%; PR rate, 41%). PFS and OS were similar in both groups. A proportional hazards regression model revealed that Durie-Salmon disease stage at diagnosis and having received three or more previous treatment regimens were the only factors that predicted PFS; the type of preparative regimen did not influence outcome. CONCLUSIONS: The results of the current study indicate that the use of a more intensive regimen did not improve results compared with HDM in patients with multiple myeloma. HDM should continue to be considered the standard preparative regimen for patients with myeloma.

Adult↗

PubMed2004

High-dose topotecan, melphalan and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of multiple myeloma.

The goal of this trial was to assess the toxicity and potential efficacy of high-dose topotecan, melphalan and cyclophosphamide as a preparative regimen for patients with multiple myeloma undergoing autologous stem cell transplantation. Eighteen patients were treated, 8 for first remission consolidation, 4 with relapse sensitive disease, 3 primary refractory and 3 relapsed refractory. The median age was 56 (38 - 65) and the median number of prior regimens was 3 (1 - 8). Patients received cyclophosphamide 1 g/m2/d on days -6, -5, -4; melphalan 70 mg/m2 on days -3, -2 and topotecan 3.0 to 3.5 mg/m2/d on days -6 to -2. Peripheral blood stem cells were infused on day 0. Toxicity (Bearman Toxicity Criteria) was mostly limited to grade 1 - 2 mucositis and grade 1 diarrhea. There were no transplant-related deaths. The overall response rate at 3 months post transplantation was 89% with 17% CR, 2 of those in refractory patients. The overall response rate in refractory patients was 67%. With a median follow up of 12.3 months, 89% of patients are alive. The TMC regimen is well tolerated and produces high response rates. Further evaluation of TMC to fully assess response and survival is ongoing.

Adult↗

PubMed2003

Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis.

Chemoresistance is a major problem in the treatment of patients with multiple myeloma (MM). Because of the central role of the nuclear transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) in chemoresistance, cell survival, and proliferation, we investigated whether MM cells derived from patients express activated NF-kappaB and STAT3 and if their suppression induces apoptosis. We assayed CD138+ cells from the bone marrow of 22 MM patients and checked for the activated forms of NF-kappaB and STAT3 by immunocytochemistry. We found that MM cells from all the patients expressed the activated forms of NF-kappaB and STAT3 but to a variable degree (NF-kappaB: low, 3 of 22; moderate, 5 of 22; or high, 14 of 22; STAT3: none, 1 of 22; low, 3 of 22; moderate, 5 of 22; or high, 14 of 22). Constitutive activation of NF-kappaB was in some cases also independently confirmed by electrophoretic mobility gel shift assay. In contrast to MM patients, activated forms of NF-kappaB and STAT3 were absent in cells from healthy individuals. Suppression of NF-kappaB and STAT3 activation in MM cells by ex vivo treatment with curcumin (diferuloylmethane) resulted in a decrease in adhesion to bone marrow stromal cells, cytokine secretion, and in the viability of cells. When compared with curcumin, dexamethasone was less effective in suppression of NF-kappaB activation and induction of apoptosis in myeloma cells. Overall, our results indicate that fresh cells from MM patients express constitutively active NF-kappaB and STAT3, and suppression of these transcription factors inhibits the survival of the cells.

Adult↗

PubMed2003

Treatment of plasma cell dyscrasias with thalidomide and its derivatives.

PURPOSE: In 1999, investigators reported promising results of a phase II study of thalidomide in patients with resistant multiple myeloma (MM). Since then, various trials of thalidomide alone and in combination with other agents have been tested in patients with resistant and, more recently, untreated MM. In addition, preliminary results of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide have been recently reported. DESIGN: We reviewed and report the results of clinical trials of thalidomide and the IMiDs, as well as the pharmacology, mechanism of action, and toxicity of these agents. RESULTS: Thalidomide has demonstrated significant activity in both resistant and previously untreated multiple myeloma. Combination therapy with dexamethasone increases response rate, even in patients previously resistant to both drugs given as single agents. More recent studies of thalidomide with dexamethasone in previously untreated patients are highly encouraging. The addition of chemotherapy to thalidomide and dexamethasone may further increase response rates, but its effect on patient survival has not been clarified. Preliminary results of trials of IMiD-3 indicate that this agent is active in resistant myeloma and has a toxicity profile different from that of thalidomide. CONCLUSION: Many studies have confirmed the activity of thalidomide in MM, as well as an improved response with dexamethasone. Newer thalidomide derivatives with reduced toxicity (neuropathy, teratogenicity) are also promising. Thalidomide with dexamethasone may now represent the treatment of choice for previously untreated patients. Further studies with these and other novel agents early in the course of myeloma may improve complete remission rates and frequency of long-term control.

Adjuvants, Immunologic↗

PubMed2003

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials.

Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation.

Adult↗

PubMed2003

Thalidomide alone or with dexamethasone for previously untreated multiple myeloma.

PURPOSE: To evaluate the activity of thalidomide in patients with asymptomatic multiple myeloma and of thalidomide-dexamethasone in patients with previously untreated symptomatic myeloma. PATIENTS AND METHODS: Twenty-eight patients with previously untreated asymptomatic myeloma were treated with thalidomide 100 to 200 mg orally (PO) at bedtime (qhs) with serial increments of 50 to 100 mg at weekly intervals, as tolerated to a maximum of 600 mg PO qhs. Forty consecutive previously untreated patients with symptomatic myeloma were also treated as above (maximum dose 400 mg) and received dexamethasone 20 mg/m(2) for 4 days beginning on days 1, 9, and 17; the second and third cycles of repeated dexamethasone were begun on day 30. Both groups of patients were treated for at least 3 months. RESULTS: The response rate was 36% for patients treated with thalidomide alone and 72% for patients treated with thalidomide-dexamethasone, the latter including complete remission in 16% of patients. The median time to remission was 4.2 months with thalidomide alone and 0.7 months with thalidomide-dexamethasone. Grade 3 toxicity included infections (nine patients) and thrombotic/embolic events (seven patients). Five deaths have occurred as a result of multiple myeloma (two patients), infection (one patient), unknown cause (one patient), and a possible thromboembolic event (one patient). CONCLUSION: Thalidomide alone was effective in patients with newly diagnosed myeloma. The combination with dexamethasone induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. These observations support further studies of this promising combination for patients with newly diagnosed multiple myeloma.

Angiogenesis Inhibitors↗

PubMed2003

Thalidomide and dexamethasone for resistant multiple myeloma.

Between November 1998 and April 2000, the combination of thalidomide and dexamethasone was evaluated in 47 consecutive patients with multiple myeloma that was resistant to prior high-dose dexamethasone-based therapies. Remission was observed in 22 patients (47%), including six patients with complete remission. Side-effects were frequent, mild and usually reversible, but deep vein thrombosis occurred in 8% of patients. Survival and remission times were longer among patients treated for previous resistant disease rather than for resistant relapse. This experience supports the use of thalidomide-dexamethasone in myeloma patients with resistant disease and justifies further trials in newly diagnosed patients.

Adult↗

PubMed2003

Thalidomide with or without dexamethasone for refractory or relapsing multiple myeloma.

Both thalidomide and intermittent high-dose dexamethasone are agents with established activity against multiple myeloma. We summarized our experience with thalidomide alone, and then in combination with dexamethasone, for groups of patients with myeloma resistant or relapsing despite standard treatments. Criteria of response were based on greater than 50% reduction of serum myeloma protein and/or greater than 75% reduction of Bence Jones protein for patients treated with thalidomide alone and greater than 75% reduction of serum myeloma protein and/or greater than 90% reduction of Bence Jones protein for those who received thalidomide with dexamethasone. Among patients with resistant or relapsing disease treated with a combination of thalidomide and dexamethasone, 47% of patients achieved remission with significant prolongation of survival for responsive patients. Among patients in stable partial remission after intensive therapy who received the same program, myeloma protein was reduced further by greater than 90% in 52% of patients who had not received prior thalidomide/dexamethasone. Side effects were frequent, mild and reversible, and often preventable. Our program of thalidomide/dexamethasone was a safe and effective combination for patients with resistant or relapsing disease, or as consolidation of partial remission after intensive therapy.

Adjuvants, Immunologic↗

PubMed2003

Uniform response criteria in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is a malignant disorder of lymphoplasmacytic cells that produce a monoclonal immunoglobulin M (IgM). Since the original description by Jan Waldenström of three patients with symptoms of hyperviscosity due to circulating monoclonal IgM, the definition of WM has been controversial. Standardized criteria for diagnosis have now been proposed, including the presence of any IgM monoclonal protein and marrow and/or nodal lymphoplasmacytic cells. Although previous response criteria have generally incorporated parameters for monoclonal protein reduction and/or improvement of marrow/nodal involvement, specific and uniform response criteria are needed to facilitate comparisons of response, remission duration, progression-free survival, and overall survival in clinical trials similar to those previously established for other diseases such as chronic lymphocytic leukemia, lymphoma, and myeloma. This is of particular importance as new agents are developed and evaluated. This presentation represents consensus recommendations for uniform response criteria for use in assessing responses to treatment for patients with WM, which were prepared in conjunction with the Second International Workshop held in Athens, Greece during September 2002.

Antineoplastic Agents↗

PubMed2002

Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of bone.

BACKGROUND: Prognostic factors for solitary plasmacytoma of bone (SPB), whether measured before or after radiotherapy (RT), have not been established. The authors analyzed multiple factors for myeloma-free survival (MFS) and cause-specific survival (CSS) in SPB patients treated with RT alone. METHODS: Between 1965 and 2000, 60 patients with carefully staged SPB were treated with RT alone at the M. D. Anderson Cancer Center. Patient ages ranged from 29-77 years (median, 54 years), and 75% of patients had a myeloma (M) protein in the blood and/or urine. No patients showed other lesions on skeletal survey or, in recent years, magnetic resonance imaging (MRI) of the spine; marrow aspirate was normal in all patients. Radiotherapy to the solitary lesion was given to a total dose of 30-70 Gy (median, 46 Gy). The authors analyzed the impact of multiple factors on MFS and CSS, including resolution v. persistence of M protein after RT, secretory v. nonsecretory disease at diagnosis, presence v. absence of an associated soft tissue mass on computed tomography or MRI scan, magnitude of serum M protein elevation at diagnosis, age, spinal v. nonspinal location, Karnofsky performance status, total RT dose, and tumor size. RESULTS: Median follow-up was 7.8 years (range, 1.0-25.5 years). On multivariate analysis, persistence of M protein more than one year after RT was the only independent adverse prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients with M protein that persisted for more than one year after RT were diagnosed with multiple myeloma within 2.2 years of treatment. CONCLUSIONS: Patients with M protein that persists for more than one year after RT should be monitored frequently and considered for standard chemotherapy followed by intensive consolidation therapy when they either develop symptoms or show an increasing M protein level.

Adult↗

PubMedDate not supplied

Thalidomide and its derivatives: new promise for multiple myeloma.

BACKGROUND: The combination of melphalan and prednisone has been accepted as standard treatment for multiple myeloma (MM) because most studies demonstrate only minimal survival benefit of combination chemotherapy regimens when compared with melphalan and prednisone. Despite modest gains with more intensive myeloablative regimens for certain subgroups, myeloma remains incurable. In 1999, investigators at the University of Arkansas reported the promising results of a phase II study of thalidomide in patients with resistant MM. Since then various trials of thalidomide alone, and in combination, have been tested in patients with resistant, and more recently, untreated MM. In addition, preliminary results of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide have recently been reported. METHODS: The author reviewed and reports the results of clinical trials of thalidomide and the IMiDs, as well as the pharmacology, mechanism of action, and toxicity of these agents. RESULTS: Thalidomide has demonstrated significant activity in both resistant and previously untreated multiple myeloma. Combination therapy with dexamethasone increases response rate, even in patients previously resistant to both drugs given as single agents, indicating probable synergy. More recent studies of thalidomide-dexamethasone in previously untreated patients are encouraging. IMiD-3 is active in resistant myeloma and has a toxicity profile different from that of thalidomide. CONCLUSIONS: Many studies have confirmed the activity of thalidomide in MM, as well as more responses with dexamethasone. Newer thalidomide derivatives with reduced toxicity are promising. Thalidomide-dexamethasone may now represent the treatment of choice for previously untreated patients. Further studies with these and other novel agents early in the course of myeloma, followed by rational programs of dose intensification, may improve complete remission rates and the frequency of long-term control.

Antineoplastic Agents↗

PubMedDate not supplied

Implementation of PET scan as a new service.

Positron emission tomography (PET) is a diagnostic test using injected radiopharmaceuticals (drugs or compounds tagged with radioactive isotopes) to obtain images of metabolic/physiologic processes. PET provides physiologic data rather than just anatomic data such as that provided by CT scan or MRI. Metabolic changes precede anatomic changes, hence the higher accuracy of PET. Scar tissue, necrosis and tumor mass may appear identical on CT and MRI, but markedly different on PET. PET may decrease unnecessary surgeries and improve treatment through greater specificity about the disease and may provide a better evaluation of recurrent disease.

Forms and Records Control↗

PubMedDate not supplied

Evaluating technology for acquisition.

Cancer care consumes approximately 8% to 9% of all healthcare spending. The use of technology plays a key role in cancer, with both diagnostic and treatment implications, and technology is a large driver of healthcare spending. Understanding the role of technology and its integration in care may contribute to appropriate selection and utilization of technology, better decision making as to priorities in acquisition, and clinical cost efficiency.

Capital Expenditures↗