title: Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph(+) ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph(+) ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.
authors.affiliation: Division of Cancer Medicine.
authors.forename: Nicholas J
authors.identifier: 0000-0002-2983-2738
authors.initials: NJ
authors.lastname: Short
authors.affiliation: Department of Leukemia, and.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, and.
authors.forename: Koji
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.affiliation: Department of Leukemia, and.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: Department of Leukemia, and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Garris
authors.affiliation: Division of Cancer Medicine.
authors.forename: Ghayas C
authors.initials: GC
authors.lastname: Issa
authors.affiliation: Department of Leukemia, and.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Leukemia, and.
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Department of Leukemia, and.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, and.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C581634:BCR-ABL1 fusion protein, human; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide; D016044:Fusion Proteins, bcr-abl; D008727:Methotrexate