title: Quantification of minimal residual disease levels by flow cytometry at time of transplant predicts outcome after myeloablative allogeneic transplantation in ALL.
abstract: The potential impact on patient outcome of different Minimal residual disease (MRD) levels at time of transplant in patients with lymphoblastic leukemia undergoing allogeneic hematopoietic SCT (HSCT) remains uncertain. In this study, we quantified MRD levels at time of transplant using multiparameter flow cytometry (MFC). Mononuclear cells from marrow aspirates were obtained from 102 adult and child patients before their conditioning regimen. Quantification of MRD levels was carried out by detecting patient-specific leukemia-associated immunophenotypes using four-color MFC. Thirty patients exhibited measurable levels of MRD at the time of transplant, with low levels (0.01 to 0.1%) in 12 cases, intermediate levels (>0.1 to 1%) in 8 cases and high levels (>1%) in 10 cases. The leukemia-free survival (LFS) rates were 65.9±7.0%, 42.9±15.7% and 0% for negative, low levels 0.1% and intermediate-high levels >0.1%, respectively (P<0.001, log-rank test). Overall survival (OS) was 52.3±7.6%, 28.6±13.8% and 0% for MRD-negative, low levels 0.1% and intermediate-high levels >0.1%, respectively (P<0.001, log-rank test). Multivariate Cox analysis confirmed that detection of leukemia cells by flow cytometry at transplant was the most significantly adverse factor for OS, LFS and EFS after transplant.
authors.affiliation: Hematology and Bone Marrow Transplantation Department, University Hospital 'Reina Sofia', Cordoba, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sanchez-Garcia
authors.forename: J
authors.initials: J
authors.lastname: Serrano
authors.forename: J
authors.initials: J
authors.lastname: Serrano-Lopez
authors.forename: P
authors.initials: P
authors.lastname: Gomez-Garcia
authors.forename: F
authors.initials: F
authors.lastname: Martinez
authors.forename: J M
authors.initials: JM
authors.lastname: Garcia-Castellano
authors.forename: R
authors.initials: R
authors.lastname: Rojas
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez-Villa
authors.forename: J R
authors.initials: JR
authors.lastname: Molina-Hurtado
authors.forename: M A
authors.initials: MA
authors.lastname: Alvarez
authors.forename: J
authors.initials: J
authors.lastname: Casaño
authors.forename: A
authors.initials: A
authors.lastname: Torres-Gomez
mesh_terms: D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology* / Q000601:surgery*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome