Leylagul Kaynar1, Koray Demir1, Esra Ermiş Turak1, Çiğdem Pala Öztürk1,2, Gökmen Zararsız3, Zeynep Burçin Gönen4, Selma Gökahmetoğlu5, Serdar Şıvgın1, Bülent Eser1, Yavuz Köker6, Musa Solmaz1, Ali Ünal1, Mustafa Çetin1. 1. a Hematology Department, Medical Faculty , Erciyes University , Kayseri , Turkey. 2. b Dışkapı Yıldırım Beyazıt Training and Research Hospital , Ankara , Turkey. 3. c Biostatistics Department, Medical Faculty , Erciyes University , Kayseri , Turkey. 4. d Genome and Stem Cell Center (GENKOK) , Erciyes University , Kayseri , Turkey. 5. e Microbiology Department, Medical Faculty , Erciyes University , Kayseri , Turkey. 6. f Immunology Department, Medical Faculty , Erciyes University , Kayseri , Turkey.
Abstract
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia. 84.4% of patients were in the high-risk group, and 55.9% were not in remission. The preparative regimen included thiotepa, melphalan, fludarabine, and anti-thymocyte globulin-Fresenius. Grafts were peripheral blood stem cells engineered by TcR-alpha/beta depletion. RESULTS: Neutrophil and platelet engraftment was achieved on days +12 (range, 10.5-15) and +11 (range, 10-12). All but three patients were engrafted with full donor chimerism. Grade III-IV acute GVHD occurred in two (5.9%) patients and chronic GVHD in two (6.1%). Disease-free survival and overall survival were 42 and 54% at 1 year, respectively. AML as disease type (HR: 4.87, 95% CI: 1.50-15.87) and mother as donor (HR: 1.05, 95% CI: 1.00-1.11) were found to be independent risk factors on patient survival. Mortality and NRM in the first 100 days were 5 of 34 (14.7%) and 4 of 34 (11.7%). Relapse was the main cause of death (56.3%). T-cell reconstitution appears to be faster than that reported in published data with CD3/CD19-depleted grafts. CONCLUSION: αβ T-cell-depleted haploidentical transplantation may be a good alternative for high-risk patients if there are no human leukocyte antigen matched donors.
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia. 84.4% of patients were in the high-risk group, and 55.9% were not in remission. The preparative regimen included thiotepa, melphalan, fludarabine, and anti-thymocyte globulin-Fresenius. Grafts were peripheral blood stem cells engineered by TcR-alpha/beta depletion. RESULTS: Neutrophil and platelet engraftment was achieved on days +12 (range, 10.5-15) and +11 (range, 10-12). All but three patients were engrafted with full donor chimerism. Grade III-IV acute GVHD occurred in two (5.9%) patients and chronic GVHD in two (6.1%). Disease-free survival and overall survival were 42 and 54% at 1 year, respectively. AML as disease type (HR: 4.87, 95% CI: 1.50-15.87) and mother as donor (HR: 1.05, 95% CI: 1.00-1.11) were found to be independent risk factors on patient survival. Mortality and NRM in the first 100 days were 5 of 34 (14.7%) and 4 of 34 (11.7%). Relapse was the main cause of death (56.3%). T-cell reconstitution appears to be faster than that reported in published data with CD3/CD19-depleted grafts. CONCLUSION: αβ T-cell-depleted haploidentical transplantation may be a good alternative for high-risk patients if there are no human leukocyte antigen matched donors.
Entities:
Keywords:
haploidentical transplantation; immune reconstitution; αβ T cell depletion
Authors: Wolfgang A Bethge; Matthias Eyrich; Stephan Mielke; Roland Meisel; Dietger Niederwieser; Paul G Schlegel; Ansgar Schulz; Johann Greil; Donald Bunjes; Arne Brecht; Jurgen Kuball; Michael Schumm; Vladan Vucinic; Markus Wiesneth; Halvard Bonig; Kasper Westinga; Stefanie Biedermann; Silke Holtkamp; Sandra Karitzky; Michaela Malchow; Christiane Siewert; Rupert Handgretinger; Peter Lang Journal: Bone Marrow Transplant Date: 2021-12-24 Impact factor: 5.174