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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4771-4779.
Prepublished online as a Blood First Edition Paper on February 11, 2009; DOI 10.1182/blood-2008-10-183723.


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TRANSPLANTATION

Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery

Anna Dodero1,*, Cristiana Carniti1,*, Anna Raganato1, Antonio Vendramin1, Lucia Farina1, Francesco Spina1, Carmelo Carlo-Stella2,3, Simona Di Terlizzi1, Marco Milanesi2, Paolo Longoni2, Lorenza Gandola4, Claudia Lombardo5, and Paolo Corradini1,6

1 Division of Hematology and Bone Marrow Transplantation and 2 Cristina Gandini Division of Medical Oncology, Istituto Nazionale dei Tumori, Milan; 3 Chair of Oncology, University of Milan, Milan; 4 Radiotherapy Department and 5 HLA Typing Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan; and 6 Chair of Hematology, University of Milan, Milan, Italy

Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34+ cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26% and the 2-year overall survival (OS) was 44%, with a better outcome for patients with chemosensitive disease (OS, 75%). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82%) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26%) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution.


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