Biomedical subjects

Mark Benyunes

Publications and source records attributed to Mark Benyunes.

3 recordsLinked to original sources

PubMed2002

Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization.

This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 microg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 microg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached > or = 2 x 10(9)/L; leukapheresis was continued until acquisition of a target dose of > or = 5 x 10(6) CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 x 10(6) CD34 cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 x 10(6) cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after high-dose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 x 10(9)/L and a platelet count of 20 x 10(9)/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.

Adult↗

PubMed2002

Rituximab in combination with CHOP or fludarabine in low-grade lymphoma.

Non-Hodgkin's lymphoma (NHL) is composed of a group of lymphoid malignancies that has been increasing in incidence at an annual rate of 4% to 7% over the last 20 years in both the United States and Europe. The reasons for this rise in incidence in NHL are not yet defined but most likely involve environmental exposures. Low-grade and follicular lymphomas account for approximately 40% of the incidences of NHL in the United States. While patients with intermediate- and high-grade lymphomas are potentially curable with combination chemotherapy, low-grade and follicular lymphomas are still considered to be essentially incurable with standard therapy. Although low-grade lymphomas characteristically respond well to treatment with chemotherapeutic agents, the disease typically follows a course of recurrent relapse and progressively shorter remissions, and ultimately death from lymphoma. Median survival for patients with low-grade lymphoma is 6.2 years from diagnosis and just 5 years from time of first relapse. Therefore, novel therapeutic strategies are urgently needed for these patients. One approach to the development of innovative strategies for treatment of NHL has been the generation of monoclonal antibodies to specific B-cell antigens expressed on NHL cells.

Antibodies, Monoclonal↗

PubMed2002

Rituximab: ongoing and future clinical development.

Monoclonal antibodies have been used as therapeutic agents for many years. In 1997, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) became the first monoclonal antibody to be approved by the US Food and Drug Administration for a cancer indication. The use of rituximab in the treatment of low-grade or follicular, relapsed, or refractory CD20-positive B-cell non-Hodgkin's lymphoma was approved in November 1997 for United States marketing under the trade name Rituxan. In June 1998, rituximab was approved for all European Union countries under the trade name MabThera as therapy for patients with stage III/IV, follicular, chemoresistant, or relapsed (> or = 2 relapses) non-Hodgkin's lymphoma. To date, rituximab has been approved in 56 countries. Over 125,000 patients have been treated with this antibody in the United States alone. Rituximab served to heighten interest in the therapeutic applications of monoclonal antibodies. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. The US Food and Drug Administration approved a new (revised) package insert in early 2001. These revisions have been communicated to physicians via a "Dear Doctor Letter" and will appear in the 2002 edition of the Physicians' Desk Reference. A significant amount of clinical research has been performed over the past 9 years, which has served to further our understanding of the potential clinical applications for this novel therapeutic agent. Ongoing and future clinical trials are reviewed in this article. However, much remains to be accomplished in key areas such as combinations with chemotherapy, biologics (including other antibodies), and radiotherapy/radioimmunotherapy; its role within multimodality regimens; and other malignant (beyond low-grade non-Hodgkin's lymphoma) and nonmalignant applications.

Antibodies, Monoclonal↗