title: Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation.
abstract: In this study, we used multiparameter flow cytometry to quantify minimal residual disease (MRD) in 165 serial bone marrow samples from 40 patients diagnosed with acute lymphoblastic leukaemia (ALL) who underwent allogeneic stem cell transplantation (allo-SCT) from siblings (n = 34) or unrelated donors (n = 6). Samples were prospectively taken from 24 patients before starting the conditioning regimen, at days +30, +60 and +90 and subsequently every 2-3 months. Samples from 16 patients in complete remission (CR) after allo-SCT were taken at least twice. Six of 24 patients harboured MRD (0.2-10% of mononuclear cells) at transplant and 18 were negative. Estimated disease-free survival for the MRD+ and MRD- groups at transplant was 33.3% and 73.5% respectively (P = 0.03). During follow-up, increasing MRD levels were detected in nine patients, a finding that preceded marrow relapse by 1-6 months. Two patients with stable low MRD levels remained in CR. When we used flow cytometry to test the effect of donor leucocyte infusions (DLI) in six patients, we observed that the only sustained remission was achieved when DLI was applied prior to overt relapse. We conclude that MRD by flow cytometry can rapidly assess tumoral burden before transplant to predict outcome, and can be clinically useful for the timing of DLI for increasing levels of leukaemia after transplant.
authors.affiliation: Haematology and Bone Marrow Transplantation Department, University Hospital Reina Sofía, Córdoba, Spain. joaquin.sanchez@cheerful.com
authors.forename: Joaquín
authors.initials: J
authors.lastname: Sánchez
authors.forename: Josefina
authors.initials: J
authors.lastname: Serrano
authors.forename: Pedro
authors.initials: P
authors.lastname: Gómez
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez
authors.forename: Carmen
authors.initials: C
authors.lastname: Martín
authors.forename: Luis
authors.initials: L
authors.lastname: Madero
authors.forename: Concepción
authors.initials: C
authors.lastname: Herrera
authors.forename: J Manuel
authors.initials: JM
authors.lastname: García
authors.forename: Javier
authors.initials: J
authors.lastname: Casaño
authors.forename: Antonio
authors.initials: A
authors.lastname: Torres
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D017708:Leukocyte Transfusion; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome