title: Stable non-transforming minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia after autologous transplantation: origin from neoplastic yet 'pre-leukemic' stem cells?
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.
authors.affiliation: Bone Marrow Transplantation Unit, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Böhm
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Mitterbauer-Hohendanner
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Hauswirth
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.forename: Margit
authors.initials: M
authors.lastname: Mitterbauer
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jäger
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology* / Q000628:therapy*; D012074:Remission Induction; D014182:Transplantation, Autologous