Graft rejection following HLA matched T‐lymphocyte depleted bone marrow transplantation

Abstract

Summary. Bone marrow graft rejection following HLA‐matched bone marrow transplantation (BMT) for leukaemia has been a rare problem. However, with the introduction of T‐lymphocyte depleted BMT, graft rejection is recognized as a new complication. At the Royal Free Hospital (RFH) in London T‐depletion is achieved using two monoclonal antibodies with complement mediated lysis. The methodology was extended to other centres and in total 56 patients have received T‐depleted, HLA matched BMT. Twelve of 56 patients have had graft rejection. At the RFH three of 41 (7%) patients have had rejection whereas at collaborating centres nine of 15 (60%) patients have had rejection. We have investigated these rejections in order to identify factor(s) responsible. Rejection was not restricted by patient or donor characteristics, nor disease status. Patient management, chemotherapy conditioning, efficiency of T‐depletion, graft versus host disease (GvHD), and infection post BMT, were not consistently implicated. The major difference between the RFH and all other centres was in the radiotherapy (RT) conditioning: The RFH prescribed a single fraction of 7‐5 Gy total body irradiation (TBI) whilst collaborating centres gave 10 or 12 Gy fractionated TBI. We conclude that the different incidence of rejection (7% v. 60%) relates primarily to the RT conditioning although the mechanisms(s) of rejection remain unknown. We conclude that where T‐depleted BMT is used, compensation by more intensive RT conditioning is required in order to avert graft rejection.

Prophylaxis and treatment of GVHD: EBMT–ELN working group recommendations for a standardized practice

“…It can be prevented by selected methods, but often at the expense of an increased risk of relapse, rejection or delayed immune reconstitution. [1][2][3] Hence, no optimal or even satisfactory prevention and treatment method can be defined. To advance our knowledge and define optimal approaches, correct information on the value of different strategies and methods in GVHD prevention and treatment is essential.…”

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

“…Negative selection can be achieved either through physical methods such as counterflow elutriation [3,4,5] or soybean lectin agglutination (SBA) and sheep red blood cell (sRBC)-rosette depletion (E-rosetting) [6,7,8,9,10], or immunological methods using monoclonal antibodies [5,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Monoclonal antibodies can be used with or without complement, or conjugated to toxins.…”

Use of T-Cell Antibodies for Donor Dosaging in a Canine Model of in utero Hematopoietic Stem Cell Transplantation

“…Multiple animal and clinical studies have shown the dichotomous role of T cells in donor engraftment and GVHD [4,5,[11][12][13][14][15] . With recently available canine CD3 and CD5 antibodies, we have advanced our model to begin to adjust the donor graft for T-cell dosaging.…”