@article{ref1,
title="Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study",
journal="Lancet oncololgy",
year="2009",
author="Ciceri, Fabio and Bonini, Chiara and Stanghellini, Maria Teresa Lupo and Bondanza, Attilio and Traversari, Catia and Salomoni, Monica and Turchetto, Lucia and Colombi, Scialini and Bernardi, Massimo and Peccatori, Jacopo and Pescarollo, Alessandra and Servida, Paolo and Magnani, Zulma and Perna, Serena K. and Valtolina, Veronica and Crippa, Fulvio and Callegaro, Luciano and Spoldi, Elena and Crocchiolo, Roberto and Fleischhauer, Katharina and Ponzoni, Maurilio and Vago, Luca and Rossini, Silvano and Santoro, Armando and Todisco, Elisabetta and Apperley, Jane and Olavarria, Eduardo and Slavin, Shimon and Weissinger, Eva M. and Ganser, Arnold and Stadler, Michael and Yannaki, Evangelia and Fassas, Athanasios and Anagnostopoulos, Achilles and Bregni, Marco and Stampino, Corrado Gallo and Bruzzi, Paolo and Bordignon, Claudio",
volume="10",
number="5",
pages="489-500",
abstract="BACKGROUND: Procedures to prevent severe graft-versus-host disease (GVHD) delay immune reconstitution secondary to transplants of haploidentical haemopoietic stem cells for the treatment of leukaemia, leading to high rates of late infectious mortality. We aimed to systematically add back genetically engineered donor lymphocytes to facilitate immune reconstitution and prevent late mortality. METHODS: In a phase I-II, multicentre, non-randomised trial of haploidentical stem-cell transplantation, we infused donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) after transplantation. The primary study endpoint was immune reconstitution defined as circulating CD3+ count of 100 cells per muL or more for two consecutive observations. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00423124. FINDINGS: From Aug 13, 2002, to March 26, 2008, 50 patients (median age 51 years, range 17-66) received haploidentical stem-cell transplants for high-risk leukaemia. Immune reconstitution was not recorded before infusion of TK-cells. 28 patients received TK-cells starting 28 days after transplantation; 22 patients obtained immune reconstitution at median 75 days (range 34-127) from transplantation and 23 days (13-42) from infusion. Ten patients developed acute GVHD (grade I-IV) and one developed chronic GVHD, which were controlled by induction of the suicide gene. Overall survival at 3 years was 49% (95% CI 25-73) for 19 patients who were in remission from primary leukaemia at the time of stem-cell transplantation. After TK-cell infusion, the last death due to infection was at 166 days, this was the only infectious death at more than 100 days. No acute or chronic adverse events were related to the gene-transfer procedure. INTERPRETATION: Infusion of TK-cells might be effective in accelerating immune reconstitution, while controlling GVHD and protecting patients from late mortality in those who are candidates for haploidentical stem-cell transplantation. FUNDING: MolMed SpA, Italian Association for Cancer Research.<p /><p>Language: en</p>",
language="en",
issn="1470-2045",
doi="10.1016/S1470-2045(09)70074-9",
url="http://dx.doi.org/10.1016/S1470-2045(09)70074-9"
}