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Research Article

A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission

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Pages 851-859 | Received 01 Mar 2012, Accepted 14 May 2012, Published online: 16 Jul 2012
 

Abstract

Background aims. Cytokine-induced killer (CIK) cells have shown remarkable cytotoxicity against various tumors in vitro and in animal studies. We report on the clinical outcome of autologous CIK cells for patients with acute (AML) and chronic (CML) myeloid leukemia in remission. Methods. Eleven of the 13 recruited AML patients undergoing autologous peripheral blood stem cell transplant (autoPBSCT) were given autologous CIK cell infusion upon engraftment post-transplant and followed-up for disease relapse. Eleven CML patients on Imatinib with residual disease detectable by polymerase chain reaction (PCR) were given infusion and monitored by quantitation of the bcr-abl transcript. Results. Despite the presence of interferon (IFN)-γ-secreting T cells against various AML- and CML-associated peptides at sporadic time-points and demonstration of in vitro cytotoxicity of CIK cells against autologous and allogeneic AML targets, there was no survival benefit in AML patients post-autoPBSCT given CIK cells compared with historical controls. For CML patients, all continued to have a detectable bcr-abl transcript fluctuating within a range comparable to their pre-treatment baseline, although two had a transient but non-sustainable disappearance of bcr-abl transcript. There were no adverse reactions except for fever within the first day of infusion. Conclusions. Our small series, while confirming safety, failed to demonstrate a clinical benefit of autologous CIK cells given in its current form for AML and CML. Further manipulation of CIK cells to improve anti-leukemic potency and specificity, together with the preparation of patients to create a more conducive milieu for in vivo expansion and persistence of infused CIK cells, should be explored.

Acknowledgements

The authors are thankful to all nursing staff in the Department of Haematology for their expert nursing care of patients, and to all patients who took part in this clinical trial. The project involving the cellular therapy facility is funded by the Singapore Cancer Syndicate grants TS39 and TS68. The clinical project for AML is funded by the Singapore National Medical Research Council grant NMCR/1097/2006, and that for CML is funded by the SingHealth Foundation PTC02/2007/005.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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