16 Penn Tower
34th and Civic Center Blvd.
Philadelphia, PA 19104

215-662-7910
215-662-4064 fax
 

Research Program
Clinical Trials in Leukemia, Myeloma and Autologous Hematopoietic Stem Cell Support

Program Summary
An interdisciplinary team of investigators is actively pursuing new treatment approaches to improve the long term survival of patients with leukemia and myeloma. We also have an active autologous stem cell transplant program that allows the use of high dose therapy for patients with advanced poor prognosis malignancies.

High-dose therapy with autologous stem cell support. Numerous studies have shown that the number of tumor cells surviving exposure to an anti-neoplastic agent decline as a logarithmic function of delivered dose. Severe and prolonged myelosuppression remains the dose limiting factor for these therapies. We are therefore utilizing autologous bone marrow and peripheral stem cell collection, processing and cryopreservation along with various hematopoietic growth factors to allow for the administration of substantially escalated doses of chemotherapy and radiation therapy with generally rapid recovery of hematopoiesis and substantially decreased treatment toxicity. A number of approaches to purge stem cells of contaminating tumor are under investigation, including chemical purging, immunological techniques, and antisense oligonucleotide strategies. More recently, we have applied these techniques for the treatment of solid tumors such as breast cancer, germ cell cancers and gliomas. Peripherally collected stem cells provide faster marrow recovery than traditional bone marrow-derived stem cells and allow for treatment of patients in whom marrow harvesting is not generally possible. Active trials are underway to further develop this technology, including improved assays for stem cells and the use of chemotherapy and hematopoietic growth factors to stimulate the release of hematopoietic progenitors into the circulation.

Leukemia and Myeloma Program. A number of laboratory and clinical studies are investigating the therapy of adult acute and chronic leukemia, myelodysplasia and multiple myeloma. Many of these studies utilize the techniques of high dose therapy with stem cell support as outlined above. Additionally, a number of novel therapeutic agents are under active clinical investigation. These include trials of trans-retinoic acid in myelodysplasia, methotrexate and PEG-L asparaginase in refractory hematologic malignancies, and m-CSF in the treatment of chronic lymphocytic leukemia. Trials in acute myeloid and lymphoid leukemia are designed primarily to allow the integration of new agents into the conventional chemotherapy of these diseases. Randomized trials are therefore underway exploring the use of hematopoietic growth factors, trans-retinoic acid and immune modulators such as linomide, in these diseases.

Associated Faculty
Selina Luger, M.D. (Medicine)
Leslie Silberstein, M.D. (Medicine)
Alan Gewirtz, M.D. (Medicine)