Biomedical subjects

Ralph M Meyer

Publications and source records attributed to Ralph M Meyer.

13 recordsLinked to original sources

PubMed2007

Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura.

BACKGROUND: Rituximab, a monoclonal anti-CD20 antibody, is increasingly used to treat idiopathic thrombocytopenic purpura (ITP). PURPOSE: To systematically review the literature on the efficacy and safety of rituximab for the treatment of adults with ITP. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, abstracts from the American Societies of Hematology and Clinical Oncology annual meetings, and bibliographies of relevant articles and reviews were searched in duplicate until April 2006. STUDY SELECTION: Descriptive and comparative studies in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. DATA EXTRACTION: Platelet count response, toxicities, dose, previous treatments, baseline platelet count, duration of ITP, study design, and sources of funding were extracted in duplicate. DATA SYNTHESIS: We identified 19 eligible reports on efficacy (313 patients) and 29 on safety (306 patients). Weighted means for complete response (platelet count > 150 x 10(9) cells/L) and overall response (platelet count > 50 x 10(9) cells/L) with rituximab were 43.6% (95% CI, 29.5% to 57.7%) and 62.5% (CI, 52.6% to 72.5%), respectively. Responses lasted from 2 to 48 months. Nearly all patients had received corticosteroids, and 53.8% had undergone splenectomy. Nine patients (2.9%) died. LIMITATIONS: There were no controlled studies, and no studies met all criteria for study quality. Reported deaths could not necessarily be attributed to rituximab. Overall, the number of rituximab-treated patients with ITP reported in the literature is small. CONCLUSIONS: Rituximab resulted in an overall platelet count response in 62.5% of adults with ITP. However, this finding derives from uncontrolled studies that also reported significant toxicities, including death in 2.9% of cases. These data suggest that providers should avoid indiscriminate use of rituximab and that randomized, controlled trials of rituximab for ITP are urgently needed.

Antibodies, Monoclonal↗

PubMed2006

A phase II study of ZD6474 (Zactima, a selective inhibitor of VEGFR and EGFR tyrosine kinase in patients with relapsed multiple myeloma--NCIC CTG IND.145.

Multiple myeloma is a disease in which angiogenesis is postulated to be a target for therapy. Based on this hypothesis, we conducted a phase II trial of ZD6474 (Zactima; a VEGFR inhibitor) 100 mg p.o. daily in patients with relapsed multiple myeloma. The primary efficacy endpoint was objective response as assessed by reduction in M protein. There were 18 patients with a mean age of 64 years. One patient was ineligible and one was not evaluable. Overall, ZD6474 was well tolerated and pharmacokinetic testing demonstrated that adequate drug levels were achieved. The most common drug-related adverse events were nausea, vomiting, fatigue, rash, pruritus, headache, diarrhea, dizziness, and sensory neuropathy, all of which were Grade I-II in severity. There were no drug-related serious adverse events. Laboratory adverse events were infrequent: one patient had Grade III anemia, and there were no Grade III changes in biochemistry. No significant QTc interval changes were seen. There were no responses in M protein levels. In conclusion, ZD6474 was well tolerated at a dose of 100 mg per day and achieved plasma levels predicted to inhibit VEGF signaling. However, this was not reflected in clinical benefit since none of the patients had a reduction in M protein.

Administration, Oral↗

PubMed2006

Yttrium 90 ibritumomab tiuxetan in lymphoma.

Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma (NHL) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns of associated toxicities and unclear long-term benefit. A comprehensive search for studies on 90Y-ibritumomab tiuxetan use in lymphoma was completed. The aims of this systematic review were to summarize and evaluate the evidence on: (1) the benefits and risks of this novel therapy; (2) predictors for response and toxicity; and (3) the role of dosimetry and imaging studies prior to treatment. A total of twenty trials investigating the use of 90Y-ibritumomab tiuxetan for the treatment of adult patients with NHL were identified. In trials of patients with relapsed or refractory indolent NHL, overall response rates ranged from 67 - 83%. In patients with follicular NHL refractory to the monoclonal antibody, rituximab, response rates remained high (74%). However, in rituximab-naïve patients with relapsed or refractory indolent or transformed NHL, the higher response rate seen with 90Y-ibritumomab tiuxetan therapy compared to rituximab monotherapy has not translated into clear improvements in time-to-progression or survival. 90Y-ibritumomab tiuxetan is an active agent in relapsed and refractory non-Hodgkin's lymphoma that should be considered in select patients.

Antibodies, Monoclonal↗

PubMed2006

The management of patients with limited-stage classical Hodgkin lymphoma.

The term limited-stage Hodgkin lymphoma refers to those patients with stage I-II disease and an absence of bulky disease. Among those patients with classical Hodgkin lymphoma, approximately one-third of patients will fall into this category. As long-term disease control can now be anticipated in more than 90% of these patients, management strategies must increasingly address the need to reduce the long-term treatment-related risks. Current treatment options include use of combined modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation or treatment with chemotherapy, currently consisting of ABVD, as a single modality. The choice of treatment between these two options involves specific trade-offs that must balance issues of disease control against long-term risk of late effects.

Combined Modality Therapy↗

PubMed2005

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group.

PURPOSE: We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma. PATIENTS AND METHODS: Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles. RESULTS: We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity. CONCLUSION: In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity.

Adult↗

PubMed2005

Autologous peripheral blood progenitor cells are a potential source of parvovirus B19 infection.

BACKGROUND: Parvovirus B19 is a cause of delayed red blood cell (RBC) engraftment after marrow transplantation (BMT). The diagnosis of parvovirus infection requires serologic and DNA testing in the context of clinical disease and characteristic marrow morphologic findings; however, the source of infection is often difficult to determine. STUDY DESIGN AND METHODS: Investigation of a case of delayed RBC engraftment and pure RBC aplasia (PRCA) occurring 3 months after autologous peripheral blood progenitor cell (PBPC) transplantation in a patient with high-risk diffuse large B-cell lymphoma. DNA testing of serum and of a sample of cryopreserved PBPCs was performed. RESULTS: Marrow morphology showed a maturational arrest of erythroid cells with giant proerythroblasts. Polymerase chain reaction and nucleic acid hybridization confirmed the presence of parvovirus DNA in the serum and in a sample of sequestered PBPCs saved at the time of PBPC harvest. PRCA resolved after the administration of intravenous immune globulin. CONCLUSION: Autologous PBPCs are a potential source of parvovirus infection, which may cause significant disease after autologous BMT.

DNA, Viral↗

PubMed2005

Is there convincing evidence for the use of chemotherapy alone in patients with limited stage Hodgkin's lymphoma?

Standard practices for patients with stages I and IIA non-bulky Hodgkin's lymphoma have evolved to include combined-modality therapy consisting of two or three cycles of ABVD and radiation therapy to the involved field. Long-term disease control can be expected in more than 90% of patients. However, long-term survival will also be dependent on the occurrence of treatment-related toxicities (late-effects) that include second cancers and cardiovascular events; deaths from these causes will outnumber those due to progressive Hodgkin's lymphoma. Data from randomized trials testing the role of chemotherapy alone are now available. These trials are based on the hypothesis that avoidance of radiation therapy will result in fewer deaths from late-effects, and that long-term survival will be at least comparable and possibly superior. With intermediate periods of follow-up, the results of these randomized trials demonstrate that with chemotherapy alone, disease control is reduced by approximately 5-7%, but this difference has not translated into a survival advantage. While further follow-up is required to evaluate longer term overall survival, current data can be interpreted as showing that a trade-off exists that requires balancing the advantage of superior disease control achieved with inclusion of radiation therapy and minimization of late-effects resulting from use of chemotherapy alone. The balance associated with this trade-off makes chemotherapy alone a legitimate treatment option; patients and clinicians need to be aware of these options in when making treatment decisions.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Results of a multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplant.

We report a multicenter, randomized phase II trial conducted to assess the tolerability of combined thalidomide and prednisone maintenance in multiple myeloma. Eligibility required administration of melphalan (200 mg/m2) with blood stem cell support within 1 year of treatment onset and initiation of maintenance within 60 to 100 days after stem cell infusion. All patients received 50 mg of prednisone by mouth on alternate days and thalidomide at a starting dose of either 200 or 400 mg daily by mouth. The primary end point was the incidence of dropout or dose reduction due to treatment toxicity within 6 months. Sixty-seven patients were enrolled. Median follow-up is 36.8 months. The primary end point was reached by 31% of patients on the 200 mg of thalidomide arm and 64% of patients on the 400 mg of thalidomide arm. Allowing for dose reduction, 76% of patients assigned to the 200 mg of thalidomide arm and 41% of patients assigned to the 400 mg of thalidomide arm remained on any maintenance therapy 18 months after registration. Eighty-eight percent of all patients dose-reduced thalidomide and 72% of all patients dose-reduced prednisone within 2 years of beginning maintenance. The median progression-free survival post-transplant is 32.3 months, or 42.2 months from diagnosis. Only the 200 mg of thalidomide arm of this trial met our definition of a tolerable maintenance therapy, defined as no dose reductions or discontinuation due to toxicity in at least 65% of patients for a minimum of 6 months, thus establishing a dosing schedule for phase III trials.

Aged↗

PubMed2004

Hodgkin's lymphoma: evolving concepts with implications for practice.

Hodgkin's lymphoma is a unique neoplasm of B lymphocytes. Recent data provide new understandings of the pathogenesis and options for staging and therapy of the disease. Three specific topics are addressed in this chapter. In Section I, Dr. Richard Ambinder reviews implications of the relationship of Epstein-Barr virus (EBV) and Hodgkin's lymphoma. This relation includes varying geographic epidemiologic associations, including varying associations with the clinical syndrome of infectious mononucleosis. There are plausible mechanisms, including processes initiated by viral proteins, by which EBV might lead to tumorigenesis. These mechanisms include promotion of genetic instability and alteration of normal processes of apoptosis. In addition to an epidemiologic association and potential role in pathogenesis, viral antigens may pose theoretical targets for anti-cancer therapies, including vaccination. In Section II, Dr. Sigrid Stroobants describes the potential role of positron emission tomographic (PET) scanning. By assessing differences in the metabolic activities of cancer cells, PET scanning may be superior to computerized tomographic scanning, which is limited to showing structural anatomical abnormalities. In patients with Hodgkin's and non-Hodgkin's lymphoma, PET scanning has been tested as an initial staging tool, to assess the rate of therapeutic response from a prognostic perspective, and to differentiate residual tumor from fibrotic masses in patients who have completed therapy. Particularly in assessing the nature of a residual mass seen with other post-therapeutic imaging modalities, PET scanning may provide unique information; very high negative predictive values have been reported. However, before this technology can be recommended for incorporation into standard management, properly conducted prospective trials are required to better evaluate the clinical utility of PET with respect to eventual patient outcomes. In Section III, Dr. Ralph Meyer reviews current data regarding the management of patients with limited-stage Hodgkin's lymphoma. Over the past decade, standard treatment has evolved to consist of combined-modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation. As this therapy continues to include radiation therapy, patients will remain at risk of long-term toxicities that include the development of second cancers and cardiovascular events. These "late-effects" now account for more deaths than those attributed to progressive Hodgkin's lymphoma. Comparative data testing the role of chemotherapy alone are now available and demonstrate that omission of radiation therapy results in small but statistically significant reduction in disease control, but no detectable differences in overall survival. Further follow-up will clarify whether chemotherapy alone is the preferred treatment option; at present patients should be informed of the trade-offs involved in choosing between this option and combined modality therapy.

Combined Modality Therapy↗

PubMed2002

Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen.

PURPOSE: To compare in a phase III study the safety and efficacy of fludarabine to that of cyclophosphamide, vincristine, and prednisone (CVP) in recurrent, low-grade, non-Hodgkin's lymphoma after previous response to systemic treatment. PATIENTS AND METHODS: Patients were randomized to fludarabine (25 mg/m(2) intravenously on days 1 to 5, every 28 days) or CVP (cyclophosphamide 750 mg/m(2) and vincristine 1.2 mg/m(2) both intravenously on day 1 and prednisone 40 mg/m(2) orally on days 1 to 5, every 21 days). The primary outcome assessed was progression-free survival (PFS); secondary outcomes included treatment-free survival (TFS), overall survival (OS), treatment-related toxicity, and quality of life (QoL) according to the European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire C-30 version 1.0 instrument. RESULTS: Ninety-one patients were randomized, 47 to fludarabine and 44 to CVP. There was no difference in response rates, with 64% (complete response [CR], 9%) for fludarabine versus 52% (CR, 7%) for CVP (P =.72). With a median follow-up of 42 months, median PFS (11 months v 9.1 months; P =.03) and TFS (15 months v 11 months; P =.02) were superior in patients receiving fludarabine. No difference in median overall survival was detected (57 months for fludarabine v 44 months for CVP; P =.95). Three patients receiving fludarabine died of treatment-related toxicity compared with none of the patients receiving CVP. Peripheral neuropathy and alopecia were more common with CVP. Patients receiving fludarabine had higher scores for social function (P =.008); no other differences in QoL were detected. CONCLUSION: In recurrent low-grade lymphoma, fludarabine improves PFS, TFS, and social function scores in comparison with CVP but does not improve OS.

Adult↗

PubMed2002

The role of high-dose chemotherapy and stem-cell transplantation in patients with multiple myeloma: a practice guideline of the Cancer Care Ontario Practice Guidelines Initiative.

The Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative has systematically reviewed the published literature and, through a consensus process, developed an evidence-based practice guideline assessing the role of stem-cell transplantation in patients with multiple myeloma. The conclusions were validated by solicited feedback from 221 practitioners across Ontario, Canada. The guideline comprises six recommendations: 1) Autologous transplantation is recommended for patients with stage II or III myeloma and good performance status. Evidence of benefit is strongest for patients who are younger than 55 years of age and have a serum creatinine level less than 150 micromol/L (<1.7 mg/dL). Physicians must use clinical judgment in recommending transplantation to other patients. 2) Allogeneic transplantation is not recommended as routine therapy. 3) Patients potentially eligible for transplantation should be referred for assessment early after diagnosis and should not be extensively exposed to alkylating agents before collection of stem cells. 4) Autologous peripheral blood stem cells should be harvested early in the patient's treatment course. The best available data suggest that transplantation is most advantageous when performed as part of initial therapy. 5) The comparative data addressing the specifics of the transplantation process are insufficient to allow definitive recommendations. In the absence of such data, a single transplant with high-dose melphalan, with or without total-body irradiation, is suggested for patients undergoing transplantation outside a clinical trial. 6) At this time, no conclusions can be reached about the role of interferon therapy after transplantation.

Age Factors↗

PubMed2002

Chemotherapy for older patients with newly diagnosed, advanced-stage, aggressive-histology non-Hodgkin lymphoma: a systematic review.

PURPOSE: To conduct a systematic review assessing chemotherapeutic regimens in patients at least 60 years of age with previously untreated, advanced-stage, aggressive-histology non-Hodgkin lymphoma. DATA SOURCES: Computerized databases were searched for reports from 1966 to April 2000. Relevant journals, textbooks, and reference lists of published articles were hand searched. Abstract reports were not considered. STUDY SELECTION: Randomized trials comparing different chemotherapy regimens were selected. Two independent assessors, who were blinded to authors, institution, and results of the report, reviewed the retrieved citations. DATA EXTRACTION: One author abstracted data on patient characteristics, study quality score, survival, disease response and control, toxicity, and quality of life; pooling was not done because of study heterogeneity. DATA SYNTHESIS: 12 randomized trials that compared chemotherapeutic regimens were reviewed. Progression-free and overall survival were improved when anthracycline-containing regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CTVP (cyclophosphamide, pirarubicin, vincristine, and prednisone), were compared with other regimens. CONCLUSIONS: For treatment of older patients with advanced-stage, aggressive-histology lymphoma who do not have significant comorbid illnesses, an anthracycline-containing regimen, such as CHOP, given in standard doses and schedule, provides for superior outcomes compared with other regimens.

Age Factors↗

PubMed2002

A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets.

BACKGROUND: Removal of the plasma supernatant from platelets before transfusion is effective in preventing acute reactions to platelets caused by cytokines. Prestorage WBC reduction of platelets may be even more effective at preventing reactions as the WBCs are removed and WBC-derived cytokines do not accumulate in this component. This study evaluates the effectiveness of plasma removal and two methods of prestorage WBC reduction for preventing acute reactions to platelets. STUDY DESIGN AND METHODS: Platelets given to adults with hematologic malignancies were randomly allocated to one of three types: plasma supernatant removed and a platelet storage solution added, whole blood-derived platelets that are prestorage WBC reduced by filtration before storage, and prestorage WBC-reduced apheresis platelets. Patients were monitored before, during, and after transfusion, and the severity of reactions was graded on a Likert scale. RESULTS: A total of 129 patients from four centers were given 1190 platelet transfusions. The overall frequency of reactions was 13.6 percent (162 of 1190), 21.3 percent (36 of 169) for the plasma-removed platelets, 11.4 percent (59 of 517) for random donor WBC-reduced platelets, and 13.3 percent (67 of 504) for apheresis WBC-reduced platelets (p=0.384). The overall frequency of severe reactions was 4.1 percent with plasma-removed platelets, 1.7 percent for whole blood-derived, prestorage WBC-reduced platelets, and 1.4 percent for prestorage WBC-reduced apheresis platelets. CONCLUSION: The frequency of reactions to plasma-removed platelets and prestorage WBC-reduced platelets was not significantly different; however, the power of the study for this comparison was low. There was no difference in the frequency of reactions to the two types of prestorage WBC-reduced platelets. The frequency of severe reactions to prestorage WBC-reduced platelets is low, occurring in only 1 to 2 percent of transfusions.

Adolescent↗