Successful bone marrow transplantation in sensitized recipients

Area of Science:

• Immunology
• Hematology
• Transplantation Science

Background:

• Patients with aplastic anemia and Wiskott-Aldrich syndrome can develop specific sensitization against their bone marrow donors.
• This pre-transplant immunity, detected via cell-mediated lysis assays, poses a potential barrier to successful engraftment.
• Non-MHC (Major Histocompatibility Complex) restricted familial transplantation antigens are implicated in this immune response.

Purpose of the Study:

• To investigate the efficacy of a multiagent immunosuppression protocol in overcoming pre-transplant immunity in patients undergoing bone marrow transplantation.
• To determine the role of antithymocyte serum (ATS) in abrogating sensitivity to non-MHC familial transplantation antigens.
• To assess whether pre-existing immune responses represent an insurmountable barrier to successful bone marrow engraftment.

Main Methods:

• Utilized antibody-independent and antibody-dependent cell-mediated lysis assays to detect donor-specific sensitization in fourteen aplastic anemia patients and one Wiskott-Aldrich syndrome patient.
• Administered a conditioning regimen including cyclophosphamide, procarbazine, and whole rabbit antithymocyte serum (ATS) to induce immunosuppression.
• Monitored engraftment success following bone marrow transplantation from sensitized donors.

Main Results:

• All fifteen patients successfully engrafted with bone marrow from their specifically sensitized donors.
• The multiagent immunosuppression protocol, notably ATS, was effective in abrogating donor-specific cellular immunity.
• Evidence suggests that pre-existing immune sensitivity can be overcome, allowing for successful transplantation.

Conclusions:

• Pre-transplant immunity against non-MHC familial transplantation antigens does not preclude successful bone marrow transplantation.
• Antithymocyte serum (ATS) plays a crucial role in erasing donor-specific sensitivity, facilitating engraftment.
• This study supports the feasibility of bone marrow transplantation even in the presence of pre-existing donor-specific immune responses.