Haematologica
HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
QUICK SEARCH:   [advanced]


     

Haematologica, Vol 92, Issue 1, 72-80 doi:10.3324/haematol.10433
Copyright © 2007 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Marijt, E.
Right arrow Articles by Falkenburg, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marijt, E.
Right arrow Articles by Falkenburg, F.

Stem Cell Transplantation

Phase I/II feasibility study evaluating the generation of leukemia-reactive cytotoxic T lymphocyte lines for treatment of patients with relapsed leukemia after allogeneic stem cell transplantation

Erik Marijt, Amon Wafelman, Menno van der Hoorn, Cornelis van Bergen, Rian Bongaerts, Simone van Luxemburg-Heijs, Joost van den Muijsenberg, Judith Olde Wolbers, Nicole van der Werff, Roel Willemze, Frederik Falkenburg

From the Departments of Hematology (EM, MvdH, CvB, RB, SvLH, JvdM, JOW, NvdW, RW, FF); Clinical Pharmacology, Leiden University Medical Center, The Netherlands PO Box 9600, 2300 RC Leiden, The Netherlands (AW)

Correspondence: Erik W.A.F. Marijt, M.D., Department of Hematology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: wafmarijt.hematology{at}lumc.nl.

Background and Objectives: Graft-versus-host-disease may be avoided and the likelihood of a graft-versus-leukemia reaction increased by infusion of in vitro-generated, leukemia-reactive, cytotoxic T lymphocyte (CTL) lines as treatment for patients with relapsed leukemia after allogeneic stem cell transplantation, instead of donor lymphocyte infusion. The aim of this phase I/II study was to assess the feasibility of large-scale in vitro generation of leukemia-reactive CTL for clinical use.

Design and Methods: Using a modified limiting dilution culture system donor T cells were stimulated with HLA-identical leukemic antigen-presenting cells. Feasibility experiments demonstrated that in 16 of 27 donor-recipient pairs tested a CTL line could be generated. Twelve of these 16 patients developed a relapse and for 11 of these 12 patients a CTL line was generated under Good Manufacturing Practice conditions.

Results: The CTL lines showed moderate to high cytotoxic activity against original recipient leukemic cells in vitro. Eight patients with a relapse received from one to seven CTL lines. One patient entered a complete remission after CTL infusion only, one entered a complete remission after combined CTL infusion and donor lymphocyte infusion, two patients had temporarily stable disease, and in four patients no response was observed.

Interpretation and Conclusions: Although the current procedure to generate these CTL lines is feasible, the strategy is logistically complex and time-consuming, and needs further improvement.

Key words: cellular immunotherapy, CTL, leukemia, allogeneic stem cell transplantation.






HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
Copyright © 2007 by the Ferrata Storti Foundation.