Major complications associated with allogeneic SCT are acute and chronic graft-versus-host disease (GVHD), both caused by the presence of donor T cells in the graft. Depending on the severity, GVHD can be associated with increased morbidity and mortality following transplantation.
The risk of acute GVHD following allogeneic transplantation from HLA matched sibling donors is between 20% and 60% despite the use of immunosuppressive agents, such as cyclosporin A, tacrolimus, methotrexate, antithymocyte globulin and corticosteroids alone or in combination. Grade II-IV (moderate to severe) acute GVHD is associated with an increased risk of transplant-related mortality. Mortality rates among patients who develop severe GVHD can be as high as 75% if the disease does not respond to immunosuppressive therapy.
Chronic GVHD is the most serious and common long-term complication of allogeneic SCT. It occurs in 30% to 70% of adults and children who survive more than 100 days post transplantation. Approximately half of affected patients have three or more involved organs, and treatment typically requires immunosuppressive medications for a median of two to three years. In a subset of patients treatment is often prolonged, with 15% receiving immune suppressive therapies seven or more years after the initial diagnosis of chronic GVHD. The morbidity and mortality associated with chronic GVHD is caused both by chronic GVHD-associated immunodeficiency and organ dysfunction and by the immune suppressive medications used to treat it
A chronic GVHD diagnosis is strongly correlated to poor quality of life, attributable to impairment of multiple organs, and/or the occurrence of secondary malignancies. Despite a variety of pharmacologic approaches, treatment of chronic GVHD remains unsatisfactory. Corticosteroids are the mainstay of therapy, but they are not always effective and their long-term use leads to multiple complications. Moreover, it has been suggested that chronic GVHD observed following peripheral blood stem cell transplantation may be more difficult to treat and require a greater duration of corticosteroid use in comparison to bone marrow. This results in a higher risk of late complications.
Therefore, the goal of allogeneic stem cell transplantation in AML is to achieve disease free survival in the absence of acute and chronic GVHD.
Many studies have shown that removing T cells from the donor graft by positive enrichment of CD34+ hematopoietic stem cells before transplantation effectively prevents GVHD. But, concerns about the potential risks of graft rejection, relapse and survival have limited the level of acceptance of this important therapeutic modus. There has, however, been a number of publications involving patients with AML that suggest a low risk of GVHD and relapse with this technology, particularly in patients transplanted in remission.
Authorized by U.S. Federal Law for use in the treatment of patients with acute myeloid leukemia (AML) in first complete remission. The effectiveness of the device for this use has not been demonstrated.
Indications for Use
The CliniMACS® CD34 Reagent System is indicated for processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA-identical, sibling donor to obtain a CD34+ cell-enriched population for hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional graft versus host disease (GVHD) prophylaxis in patients with acute myeloid leukemia (AML) in first morphologic complete remission.
Do not use CD34+ cells prepared with CliniMACS CD34 Reagent System in patients with known hypersensitivity to murine (mouse) proteins or iron dextran.