title: Myeloid mixed chimerism is associated with relapse in bcr-abl positive patients after unmanipulated allogeneic bone marrow transplantation for chronic myelogenous leukemia.
abstract: OBJECTIVE
  Although bcr-abl polymerase chain reaction (PCR) positivity after bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) is significantly related to relapse, the predictive value of the assay is not very high and therefore most investigators consider that qualitative RT-PCR data alone are too imprecise to enable clinical decisions to be taken in individual cases. To define the clinical outcome of bcr-abl positive patients after unmanipulated BMT better, we sought the origin of hematopoiesis and traced its evolution over time.
  
  
  METHODS
  Forty-nine patients received allogeneic BMT for CML (39 in chronic phase and 10 in accelerated phase/blast crisis). Median follow-up was 61 months (range 4-92). mRNA and DNA were used to assess bcr-abl and chimerism status respectively. Quantitative VNTR-PCR on total cells and lymphoid or myeloid population allowed us to assign and measure the origin of hematopoiesis.
  
  
  RESULTS
  Both bcr-abl positivity and the presence of mixed chimerism (MC) were significantly associated with relapse (p = 0.0009 and p < 0.0001 respectively). Relapse was observed in one of 39 patients with complete donor chimerism and in 6 of 9 patients with MC. These six cases showed increasing levels of host hemopoiesis and bcr-abl positivity in the CD15-positive population prior to relapse. The other three cases had decreasing or stable low-level MC which was restricted to the T-cells as well as bcr-abl negativity.
  
  
  CONCLUSIONS
  Whereas the simple detection of bcr-abl fails to identify patients who will relapse with certainty, the assessment of MC by VNTR-PCR does identify patients headed to relapse. Confirmation of myeloid involvement and increasing levels over time further elucidates the clinical outcome of bcr-abl positive patients after BMT.
authors.affiliation: Servicio de Hematología, Hospital Reina Sofía, 14004 Cordoba, Spain. jose.roman@iname.com.
authors.forename: J
authors.initials: J
authors.lastname: Román
authors.forename: J
authors.initials: J
authors.lastname: Serrano
authors.forename: A
authors.initials: A
authors.lastname: Jiménez
authors.forename: J A
authors.initials: JA
authors.lastname: Castillejo
authors.forename: M L
authors.initials: ML
authors.lastname: Reina
authors.forename: M G
authors.initials: MG
authors.lastname: González
authors.forename: M C
authors.initials: MC
authors.lastname: Rodríguez
authors.forename: I
authors.initials: I
authors.lastname: García
authors.forename: J
authors.initials: J
authors.lastname: Sánchez
authors.forename: J
authors.initials: J
authors.lastname: Maldonado
authors.forename: A
authors.initials: A
authors.lastname: Torres
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D016044:Fusion Proteins, bcr-abl