chapter  25
12 Pages

Prevention of Acute Graft-Versus-Host Disease by Delayed or Selected Lymphocyte Add Back

ByJohn Barrett, Dimitrios Mavroudis

I. INTRODUCTION Bone marrow transplants (BMTs) or peripheral blood stem cell transplants confer on the recipient not only donor-derived hematopoietic engraftment but also donor immunological reconstitution. For a successful outcome, engraftment should be prompt, complete, and sustained; leukemia must be eradicated; and immunity against a spectrum of pathogenic microorganisms restored. Tolerance between the donor and the host is a prerequisite for long-term survival. With new approaches, the engraftment barrier can be overcome, even in human leucocyte antigen (HLA)–mismatched situations, by increasing the stem cell dose with granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood progenitor cells (1,2) and by increasing the immunosuppressive capacity of the preparative regimen (3,4). After hematopoietic engraftment, immune recovery becomes the key issue. The donor alloresponse to the leukemia-the so-called graft-versus-leukemia (GVL) effect-contributes to the cure of the leukemia (5). On the other hand, the alloresponse also causes graft-versus-host disease (GVHD), delaying immunological reconstitution, predisposing to serious infections, and causing major organ damage and death (6). Since the nature of the immune recovery largely determines the outcome after the transplant, the separation of GVL and GVHD reactions has become an area of intensive research. Table 1 presents some of the new strategies to improve immunological recovery currently under investigation.