Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia. This is an eight-year followup to our previous study showing a survival advantage to patients with an increased cd T cells following ASCT. cd T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n ¼ 77; acute myelogenous leukemia (AML) n ¼ 76) undergoing partially mismatched related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity of three antigens was 37% in the graft-versushost disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n ¼ 46) or OKT3 (n ¼ 107). Five years LFS and overall survival (OS) of patients with increased cd compared to those with normal/decreased numbers were 54.4 vs 19.1%; Po0.0003, and 70.8 vs 19.6% Po0.0001, respectively, with no difference in GvHD (P ¼ 0.96). In a Cox multivariate analysis, normal/decreased cd (hazard ratio (HR) 4.26, P ¼ 0.0002) and sex mismatch (HR 1.45 P ¼ 0.049) were associated with inferior LFS. In conclusion, cd T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD. Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.
Summary:Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of ␥␦ + T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived V␦1 + CD4 − CD8 − ␥␦ + T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, ␥␦ + T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic ␥␦ + T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease. Bone Marrow Transplantation (2001) 27, 601-606.
Cytomegalovirus (CMV) reactivation in immunocompromised recipients of allogeneic stem cell transplantation is a cause of morbidity and mortality from viral pneumonitis. Antiviral drugs given to reactivating patients have reduced the mortality from CMV but have toxic side effects and do not always prevent late CMV disease. Cellular immunotherapy to prevent CMV disease is less toxic and could provide prolonged protection. However, a practical approach to generating sufficient quantities of CMV-specific cytotoxic T cells (CTLs) is required. This study describes a system for generating sufficient CMV-specific CTLs for adoptive immuno-
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