title: Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia.
abstract: Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has a dismal prognosis. We prospectively evaluated minimal residual disease (MRD) by measuring BCR/ ABL levels with a quantitative real-time PCR procedure after induction and after consolidation in 45 adults with Ph+ ALL who obtained complete hematological remission after a high-dose daunorubicin induction schedule. At diagnosis, the mean BCR-ABL/GUS ratio was 1.55 +/- 1.78. A total of 42 patients evaluable for outcome analysis were operationally divided into two MRD groups: good molecular responders (GMRs; n = 28) with > 2 log reduction of residual disease after induction and > 3 log reduction after consolidation therapy, and poor molecular responders (PMRs; n = 14) who, despite complete hematological remission, had a higher MRD at both time points. In GMR, the actuarial probability of relapse-free, disease-free and overall survival at two years was 38, 27 and 48%, respectively, as compared to 0, 0 and 0% in PMR (P = 0.0035, 0.0076 and 0.0026, respectively). Salvage therapy induced a second sustained complete hematological remission in three GMR patients, but in no PMR patient. Our data indicate that, as already shown in children, adult Ph+ ALL patients have a heterogeneous sensitivity to treatment, and that early quantification of residual disease is a prognostic parameter in this disease.
authors.affiliation: CEINGE - Biotecnologie Avanzate and Dipartimento di Biochimica e Biotecnologie Mediche, University 'Federico II di Napolì, Italy. fabpane@unina.it
authors.forename: F
authors.initials: F
authors.lastname: Pane
authors.forename: G
authors.initials: G
authors.lastname: Cimino
authors.forename: B
authors.initials: B
authors.lastname: Izzo
authors.forename: A
authors.initials: A
authors.lastname: Camera
authors.forename: A
authors.initials: A
authors.lastname: Vitale
authors.forename: C
authors.initials: C
authors.lastname: Quintarelli
authors.forename: M
authors.initials: M
authors.lastname: Picardi
authors.forename: G
authors.initials: G
authors.lastname: Specchia
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.forename: B
authors.initials: B
authors.lastname: Rotoli
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
authors.forename: F
authors.initials: F
authors.lastname: Salvatore
authors.forename: R
authors.initials: R
authors.lastname: Foà
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003561:Cytarabine; D014750:Vincristine; D016044:Fusion Proteins, bcr-abl; D001215:Asparaginase; D003630:Daunorubicin