Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 39; no. 12; pp. 751 - 757
• Main Authors: GODDER, K. T, HENSLEE-DOWNEY, P. J, MEHTA, J, PARK, B. S, CHIANG, K.-Y, ABHYANKAR, S, LAMB, L. S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2007
• Subjects: Acute lymphoblastic leukemia; Acute myeloid leukemia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Care and treatment; Genetic aspects; Graft rejection; Graft versus host disease; Graft-versus-host reaction; Grafting; Histocompatibility antigen HLA; Immunotherapy; Leukemia; Leukocytes; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Medical sciences; Methods; Multivariate analysis; Stem cell transplantation; Stem cells; Survival; T cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplants & implants; United States; Human; Incompatibility; γδ T cells; Hematology; mismatched related donor; γ/δ T cell receptor; Stem cell; Related donor; Hematopoietic cell; Homograft; Acute leukemia; Long term; T-Lymphocyte; Bone marrow; hematopoietic stem cell transplantation; Graft; Histocompatibility; Disease free survival
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1705650

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 follow-up to our previous study showing a survival advantage to patients with an increased γδ T cells following ASCT. γδ T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n=77; acute myelogenous leukemia (AML) n=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-versus-host disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n=46) or OKT3 (n=107). Five years LFS and overall survival (OS) of patients with increased γδ compared to those with normal/decreased numbers were 54.4 vs 19.1%; P<0.0003, and 70.8 vs 19.6% P<0.0001, respectively, with no difference in GvHD (P=0.96). In a Cox multivariate analysis, normal/decreased γδ (hazard ratio (HR) 4.26, P=0.0002) and sex mismatch (HR 1.45 P=0.049) were associated with inferior LFS. In conclusion, γδ 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.