Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
Condition: Chronic Lymphocytic Leukemia; Graft vs Host Disease; Leukemia; Myelodysplastic Syndrome; Myeloid Leukemia
MeSH terms: Leukemia; Preleukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Graft vs Host Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      Diseases such as leukemia, lymphoma, and multiple myeloma fall into the category of blood
      cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). The
      ability of BMT to cure these conditions has been credited to the use of high doses of
      chemotherapy, radiation therapy, and the antileukemia effect of the transplant.

      Because the effectiveness of BMT relies on the use of high doses of chemotherapy and total
      body irradiation (TBI), it is a therapy associated with toxic side effects. These side
      effects are often deadly and have limited BMT for use in patients under the age of 55.

      In this study researchers plan to treat older patients between the ages of 55 to 75 years
      with blood cell transplants taken from donors who are genetically matched relatives of the
      patient. In order to decrease the toxic side effects associated with the transplant,
      researchers will not use chemoradiotherapy. Instead they plan to use intensive
      immunosuppressive therapy and allow the transplanted cells to take effect.
    

Detailed description: 
      Patients with adult leukemias, non-Hodgkin's lymphoma and multiple myeloma, can now be cured
      by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to
      the use of high dose chemoradiotherapy and the antileukemia effect of the graft.

      The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and
      total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation
      in adults to those under the age of 55 years. Toxicity related mortality increases
      progressively with age and although some transplant centers carry out BMT in patients up to
      the age of 60 years, it is generally accepted that treatment related mortality prohibits the
      use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.

      Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8
      positive lymphocytes with specific reactivity for the patients leukemia and a potent graft
      versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML after
      bone marrow transplantation where a single infusion of donor lymphocytes can induce complete
      remission.

      In this protocol, we treat older patients between the ages of 55 to 71 years with hematologic
      disorders with an allogeneic stem cell transplant from an HLA identical sibling, using
      intensive immunosuppressive regimen without myeloablation in attempts to decrease the
      transplant related toxicity while preserving the antileukemia effect of the graft. The low
      intensity nonmyeloablative conditioning regimen will provide adequate immunosuppression to
      allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony
      stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) will be used to
      establish hematopoietic and lymphoid immune reconstitution. We will add back lymphocytes in
      patients with less than 75% donor marrow chimerism as an attempt to prevent graft rejection.

      The end points of this study are engraftment, degree of donor-host chimerism, incidence of
      acute and chronic GVHD, transplant related morbidity and mortality as well as survival.
    

Intervention name(s): Blood cell transplantation
Intervention type(s): Procedure
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Peripheral Blood Stem Cells; Engraftment; Fludarabine; Nonmyeloablative; Graft-Versus-Leukemia; Graft vs. Host Disease; Cyclophosphamide; Donor Apheresis; Nonmyeloablative Bone Marrow Transplantation; Chronic Myelogenous Leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Acute Myelogenous Leukemia (AML); Myelodysplastic Syndromes; Chronic Lymphocytic Leukemia (CLL); Prolymphocytic Leukemia