title: Significance of recurrence of minimal residual disease detected by multi-parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission.
abstract: We sought to determine the significance of minimal residual disease (MRD) relapse in patients with ALL after achieving MRD negative status following induction and consolidation therapy. Between January 2003 and September 2014, 647 newly diagnosed patients were treated [HyperCVAD-based (n = 531); Augmented BFM (n = 116)]. Six hundred and one (93%) achieved complete remission (CR), and 546 (91%) became MRD negative. Fifty-five patients [HyperCVAD-based (n = 49); Augmented BFM (n = 6)] developed recurrence of MRD while still in morphological CR and are the subjects of this study. MRD was assessed by 6-color (4-color prior to 2009) multi-parameter flow cytometry (MFC) at CR and multiple time points thereafter. Their median age was 44 years (range, 18-72 years), median WBC at initial presentation was 7.3 K/µL-1(range, 0.6-303.8 K/µL-1) and median bone marrow blast percentage 88% (range, 26-98%). The median time to MRD relapse was 14 months (range 3-58 months). Forty-four (80%) patients subsequently developed morphological relapse after median of 3 months (range, <1-33 months) from detection of MRD recurrence. Treatments received after MRD positivity and prior to morphological relapse: 16 continued maintenance chemotherapy; 15 received late intensification; 9 allogeneic stem cell transplant, 9 changed chemotherapy, 6 no further therapy. Only six remain alive and in CR1 and nine are alive after morphological relapse. MRD relapse detected by MFC at any time after achieving CR is associated with a high risk for morphological relapse. SCT can result in long-term remission in some patients. Prospective studies of long-term MRD assessments, together with less toxic treatment strategies to eradicate MRD, are warranted.
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naveen
authors.identifier: http://orcid.org/0000-0002-1670-6513
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elias
authors.identifier: http://orcid.org/0000-0003-4465-6119
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Division of Hematology/Oncology, University of California, Chao Family Comprehensive Cancer Center, Irvine, California.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Texas.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Texas.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sergej
authors.initials: S
authors.lastname: Konoplev
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Garris
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005434:Flow Cytometry / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000000981:diagnostic imaging*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult