title: Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation.
abstract: Since the incorporation of tyrosine kinase inhibitors into the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the notion that all patients with "high-risk" ALL uniformly require allogeneic (allo) hematopoietic cell transplantation (HCT) has received increasing scrutiny. Although multiple studies have shown superiority of alloHCT over autologous (auto) hematopoietic cell transplantation for high-risk patients, these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. We retrospectively evaluated minimal residual disease (MRD) using next-generation sequencing (NGS) in the PBPC leukapheresis product of 32 ALL patients who underwent autoHCT. Twenty-eight patients (88%) had diagnostic samples with quantifiable immunoreceptor rearrangements to follow for MRD. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Philadelphia chromosome-negative (Ph-) B-ALL, and 4 (14%) had T cell ALL. With a median follow-up of 41 months (range, 3 to 217), median relapse-free survival (RFS) and overall survival for the entire cohort were 3.2 and 4.2 years, respectively; at 5 years after transplantation, 42% of patients remain alive and relapse free. Using MRD detection at a threshold of ≥ 1 × 10(-6), median RFS for patients with detectable MRD was 6.5 months and was not reached for patients without detectable disease (P = .0005). In multivariate analysis, the only factor significantly associated with relapse was the presence of MRD ≥1 × 10(-6) (odds ratio, 23.8; confidence interval, 1.8 to 312.9; P = .0158). Our findings suggest that NGS for MRD detection can predict long-term RFS in patients undergoing autoHCT for high-risk ALL.
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Mannis
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Martin
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Damon
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Andreadis
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Olin
authors.affiliation: Adaptive Biotechnologies Corp., South San Francisco, California.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Kong
authors.affiliation: Adaptive Biotechnologies Corp., South San Francisco, California.
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.affiliation: Department of Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Weiyun Z
authors.initials: WZ
authors.lastname: Ai
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Karin M L
authors.initials: KML
authors.lastname: Gaensler
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sayre
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wolf
authors.affiliation: Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California. Electronic address: aaron.logan@ucsf.edu.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Logan
mesh_terms: D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000592:standards*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis*; D010677:Philadelphia Chromosome; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D014182:Transplantation, Autologous; D055815:Young Adult
keywords: Acute; Autologous; Leukemia; Lymphoblastic; Minimal residual disease; Transplantation