Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear.



This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission.



MRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with longer event-free survival (EFS; median, 18 vs 7 months; 2-year EFS rate, 46% vs 17%; P = .06) and overall survival (OS; median, 27 vs 9 months; 2-year OS, 52% vs 36%; P = .15). EFS and OS were similar in S2, regardless of the MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplantation (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than S2 (P = .003 and P = .04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes with a 2-year OS rate of 65%.



Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long-term survival. Patients in S2 generally have poor outcomes, regardless of their MRD status. Cancer 2017;123:294-302. © 2016 American Cancer Society.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Elias
E
Jabbour
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Nicholas J
NJ
Short
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jeffrey L
JL
Jorgensen
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Musa
M
Yilmaz
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Farhad
F
Ravandi
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sa A
SA
Wang
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Deborah A
DA
Thomas
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Joseph
J
Khoury
Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Richard E
RE
Champlin
Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Issa
I
Khouri
Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Partow
P
Kebriaei
Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California.
Susan M
SM
O'Brien
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Guillermo
G
Garcia-Manero
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jorge E
JE
Cortes
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Koji
K
Sasaki
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Courtney D
CD
Dinardo
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Tapan M
TM
Kadia
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Nitin
N
Jain
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Marina
M
Konopleva
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Rebecca
R
Garris
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Hagop M
HM
Kantarjian
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology*; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology; D018365:Neoplasm, Residual / Q000473:pathology*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000473:pathology*; D016879:Salvage Therapy / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods; D055815:Young Adult
D000970:Antineoplastic Agents
acute lymphoblastic leukemia; blinatumomab; inotuzumab; minimal residual disease; refractory; relapsed