193
Views
7
CrossRef citations to date
0
Altmetric
Original Articles: Clinical

Stable non-transforming minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia after autologous transplantation: origin from neoplastic yet ‘pre-leukemic’ stem cells?

, , , , , , , , & show all
Pages 842-848 | Received 22 Nov 2010, Accepted 18 Jan 2011, Published online: 04 Apr 2011
 

Abstract

In acute lymphoblastic leukemia (ALL), the Philadelphia chromosome (Ph) is associated with a poor prognosis. For these patients, hematopoietic stem cell transplantation (HSCT) and BCR/ABL tyrosine kinase inhibitors (TKIs) are considered standard of therapy. However, it remains unclear whether BCR/ABL TKIs should be administered lifelong as maintenance post-HSCT, and whether the presence of minimal residual disease (MRD) is invariably associated with relapse. We report on two patients with Ph+ ALL who were successfully treated with polychemotherapy and consecutive autologous HSCT. Both patients are in continuous hematologic remission after an observation period of 12 years and 18 years, respectively, despite measurable MRD and although no maintenance therapy was initiated. BCR/ABL transcript-levels ranged between 0.1 and 3% in patient 1, and 0.01 and 0.1% in patient 2 during the observation time. Collectively, these data suggest that not all Ph+ subclones even those that persist after HSCT in Ph+ ALL, may have the potential to cause a hematologic relapse. We hypothesize that these small-sized clones are derived from neoplastic stem cells that have not (yet) accumulated a sufficient number of pro-oncogenic hits required for full transformation to ALL-initiating (stem) cells and thus overt leukemia.

Acknowledgements

This study was supported by the ‘Fonds zur Förderung der Wissenschaftlichen Forschung in Österreich’ (FWF) and a Cancer Stem Cell grant from the Medical University of Vienna, Austria. We would like to thank Sabine Cerny-Reiterer and Gregor Hörmann for skilful technical assistance, Günther Hofbauer and Andreas Spittler (Cell Sorting Core Unit of the Medical University of Vienna) for technical support, and Matthias Mayerhofer and Christine Mannhalter for helpful discussion.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,065.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.