title: Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia.
abstract: OBJECTIVE
  The molecular analysis of minimal residual disease (MRD) may provide information on the risk of recurrence in patients with acute lymphoblastic leukemia (ALL). The aim of this study was to correlate the kinetics of MRD clearance after allogeneic transplantation with the clinical outcome of adults with ALL.
  
  
  METHODS
  MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) using probes derived from fusion chimeric genes (BCR/ABL and MLL/AF4) (n=22) or rearrangements of the T-cell receptor or immunoglobulin genes (n=21). Forty-three adult patients with ALL were studied to correlate the kinetics of MRD clearance before and after allogeneic hematopoietic stem cell transplantation.
  
  
  RESULTS
  At 36 months, the overall survival of patients who underwent transplantation in hematologic remission (n= 37) was 80% for those who were PCR-negative before transplantation (n= 12) compared to 49% for PCR-positive patients (n= 25)(p=0.17). For the same patients the cumulative incidence of relapse was 0% and 46%, respectively (p=0.027). Moreover, the relapse rate of patients who were PCR-negative at day +100 after transplantation was remarkably low (7%) compared to that among patients who were PCR-positive (80%, p=0.0006).
  
  
  CONCLUSIONS
  The kinetics of MRD clearance may help to identify patients at high risk of leukemia relapse after allogeneic stem cell transplantation. Patients not achieving an early molecular remission after transplantation require prompt and appropriate pre-emptive treatments such as infusions of donor lymphocytes or new experimental drugs.
authors.affiliation: Hematology and Bone Marrow Transplantation Units of Ospedali Riuniti Bergamo, Bergamo, Italy.
authors.forename: Orietta
authors.initials: O
authors.lastname: Spinelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Peruta
authors.forename: Manuela
authors.initials: M
authors.lastname: Tosi
authors.forename: Vittoria
authors.initials: V
authors.lastname: Guerini
authors.forename: Anna
authors.initials: A
authors.lastname: Salvi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Zanotti
authors.forename: Elena
authors.initials: E
authors.lastname: Oldani
authors.forename: Anna
authors.initials: A
authors.lastname: Grassi
authors.forename: Tamara
authors.initials: T
authors.lastname: Intermesoli
authors.forename: Caterina
authors.initials: C
authors.lastname: Micò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Pietro
authors.initials: P
authors.lastname: Fabris
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lambertenghi-Deliliers
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Renato
authors.initials: R
authors.lastname: Bassan
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D017353:Gene Deletion; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D007700:Kinetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D051788:Myeloid-Lymphoid Leukemia Protein / Q000097:blood; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000097:blood; D010879:Piperazines / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D015996:Survival Rate; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014178:Translocation, Genetic; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001549:Benzamides; D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl; D000068877:Imatinib Mesylate; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C113855:MLL-AF4 fusion protein, human; C067143:TAL1 protein, human