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Stem Cell Related Patent Number US6544787
| Title: | Non-myeloablative/lymphoablative conditioning regimen to induce patient anti-donor unresponsiveness in stem cell transplantation | | Inventors: | Slavin, Shimon; Jerusalem, Israel | | Summary: | This invention introduces a method of inducing anti-donor unresponsiveness in a patient undergoing stem cell transplantation. Described herein is a process of treating pathogenic cell diseases by subjecting a patient to a lymphoablative or myeloablative conditioning regimen which is then followed by the administration of a donor-derived stem cell preparation. Such a conditioning regimen comprises the treatment of serious hematologic malignancies via high dose or lethal chemotherapy and/or radiation therapy which is then followed by rescue with allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (ASCT). Central to the invention is the fact that myeloablative/lymphoablative (M/L) treatment regimens which eliminate both the patient's hematopoietic stem cells and T-lymphocytes often lead to serious complications including graft-versus-host disease (GVHD). Disclosed herein are methods of addressing such problems via a conditioning regimen that is designed to eliminate the patient's T-lymphocytes while retaining a functional population of hematopoietic stem cells (HSC), and which involves the administration of one or more agents such as purine analogs (fludarabine), alkylating agents (bisulfan, cyclophosphamide), or anti-leukocyte globulins (anti-T lymphocyte globulin), which is followed by the administration of a donor-derived allogeneic stem cell preparation to the patient. Claims of the invention include donor-specific unresponsiveness in patients and relatively fewer complications when compared to standard M/L conditioning regimens. Therapeutic applications include the use of such a procedure in the treatment of solid tumors and hematologic malignancies such as chronic myelogenous leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma. | | Abstract: | Serious hematologic malignancies are treated through high dose or lethal chemotherapy and/or radiation therapy conditioning regimens followed by rescue with allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (ASCT). These myeloablative/lymphoablative (M/L) treatment regimens involve the elimination of both the patient's hematopoietic stem cells and T-lymphocytes, often leading to serious complications including graft versus host disease (GVHD). The claimed invention addresses some of these problems by providing a conditioning regimen that is designed to eliminate the patient's T-lymphocytes while retaining a functional population of hematopoietic stem cells (HSC). This non-myeloablative/lymphoablative (-/L) conditioning regimen involves the administration of one or more agents such as purine analogs (e.g., fludarabine), alkylating agents (e.g., bisulfan, cyclophosphamide), or anti-leukocyte globulins (e.g., anti-T lymphocyte globulin). After this, a donor-derived allogeneic stem cell preparation is administered to the patient. Patients treated according to the claimed invention develop donor-specific unresponsiveness and relatively fewer complications as compared to standard M/L conditioning regimens. The claimed methodologies should prove useful in the treatment of a number of hematologic malignancies such as chronic myelogenous leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma. | | US Patent Website: | Click Here for Full Text of Patent | | Title Number: | US6544787 | | Application Number: | US1997000995049 | | Date Filed: | 14/11/1997 | | Date Published: | 08/04/2003 | | Assignee: | Hadash Medical Research Services and Development Ltd., Jerusalem, Israel
Baxter International Inc., Deerfield, IL, USA |
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