New conditioning regimens for high risk marrow transplants

Richard J Jones, G. W. Santos

Research output: Contribution to journalArticle

Abstract

Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA). We report our preliminary results of a phase 1 dose-escalation trial evaluating the combination of busulfan, etoposide, and cyclophosphamide as a preparative regimen for patients undergoing BMT, as well as our initial results of a trial which studies the use of CSA to induce GVHD in recipients of autologous BMT.

Original languageEnglish (US)
Pages (from-to)15-17
Number of pages3
JournalBone Marrow Transplantation
Volume4
Issue numberSUPPL. 4
StatePublished - 1989

Fingerprint

Bone Marrow Transplantation
Bone Marrow
Transplants
Autologous Transplantation
Recurrence
Graft vs Host Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Homologous Transplantation
Non-Hodgkin's Lymphoma
Cyclophosphamide
Busulfan
Etoposide
Hodgkin Disease
Isogeneic Transplantation
Blast Crisis
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cyclosporine
Lymphoma
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

New conditioning regimens for high risk marrow transplants. / Jones, Richard J; Santos, G. W.

In: Bone Marrow Transplantation, Vol. 4, No. SUPPL. 4, 1989, p. 15-17.

Research output: Contribution to journalArticle

@article{41e47f33c1b040439723b331348b7237,
title = "New conditioning regimens for high risk marrow transplants",
abstract = "Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30{\%} for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50{\%} following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80{\%} in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50{\%} in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA). We report our preliminary results of a phase 1 dose-escalation trial evaluating the combination of busulfan, etoposide, and cyclophosphamide as a preparative regimen for patients undergoing BMT, as well as our initial results of a trial which studies the use of CSA to induce GVHD in recipients of autologous BMT.",
author = "Jones, {Richard J} and Santos, {G. W.}",
year = "1989",
language = "English (US)",
volume = "4",
pages = "15--17",
journal = "Bone Marrow Transplantation",
issn = "0268-3369",
publisher = "Nature Publishing Group",
number = "SUPPL. 4",

}

TY - JOUR

T1 - New conditioning regimens for high risk marrow transplants

AU - Jones, Richard J

AU - Santos, G. W.

PY - 1989

Y1 - 1989

N2 - Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA). We report our preliminary results of a phase 1 dose-escalation trial evaluating the combination of busulfan, etoposide, and cyclophosphamide as a preparative regimen for patients undergoing BMT, as well as our initial results of a trial which studies the use of CSA to induce GVHD in recipients of autologous BMT.

AB - Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA). We report our preliminary results of a phase 1 dose-escalation trial evaluating the combination of busulfan, etoposide, and cyclophosphamide as a preparative regimen for patients undergoing BMT, as well as our initial results of a trial which studies the use of CSA to induce GVHD in recipients of autologous BMT.

UR - http://www.scopus.com/inward/record.url?scp=0024949752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024949752&partnerID=8YFLogxK

M3 - Article

C2 - 2627618

AN - SCOPUS:0024949752

VL - 4

SP - 15

EP - 17

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

SN - 0268-3369

IS - SUPPL. 4

ER -