학술논문

Donor leukocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual donor T cells
Document Type
Original Paper
Source
Bone Marrow Transplantation: Official journal of the European Society for Blood and Marrow Transplantation. 22(11):1057-1063
Subject
allogeneic BMT
donor leukocyte infusions
recurrent haematologic malignancies
T cell chimerism
Language
English
ISSN
0268-3369
1476-5365
Abstract
We evaluated the efficacy and toxicity of different doses of donor T cells given with donor leukocyte infusions (DLI) as treatment for relapse of various hematologic malignancies after allogeneic bone marrow transplantation (BMT). We also studied whether DLI treatment was more effective if circulating T cells were exclusively of donor origin (complete donor T cell chimeras) as compared with T cells originating from both donor and recipient (mixed T cell chimeras). Twenty-eight patients were studied of whom 24 had a complete donor T cell chimerism. The malignancies were as follows: chronic myeloid leukemia (CML) in chronic phase (CP) (n = 9); more advanced CML (n = 5); multiple myeloma (MM) (n = 5); acute leukemia (AL) (n = 9). T cell doses varied from 0.1 × 107 to 33 × 107 T cells/kg. Eight patients received two to four DLI courses because they failed to respond to one course. Thirteen of 14 patients with CML, including four patients with more advanced CML, achieved complete remission (CR). All five patients with MM responded, including three CRs. Six patients (three with CML, three with MM) responded only after two to four DLI courses. Patients with CML-CP were likely to respond to as few as 1 × 107 T cells/kg whereas patients with MM generally responded when they received ⩾10 × 107 T cells/kg. However, despite the infusion of high T cell doses (up to 32 × 107 T cells/kg), practically all patients with AL failed to respond. The likelihood of response was strongly related to the occurrence of graft-versus-host disease (GVHD) in patients with CML and MM (P = 0.0002), although GVHD was not helpful for patients with AL. Higher T cell doses (⩾10 × 107/kg) induced serious GVHD (n = 17) and marrow aplasia (n = 5), and GVHD was directly or indirectly the cause of death for six patients. Finally, there were no obvious differences in responses between complete donor T cell chimeras and mixed T cell chimeras.