title: Real Time Immunophenotyping of Leukocyte Subsets Early after Double Cord Blood Transplantation Predicts Graft Function.
abstract: Cord blood transplantation (CBT) recipients are at increased risk for delayed engraftment and primary graft failure, complications that are often indistinguishable early post-transplantation. Current assays fail to accurately identify recipients with slow hematopoietic recovery and distinguish them from those with pending graft failure. To address this, we prospectively examined the kinetics of immune cell subset recovery in the peripheral blood of 39 patients on days +7 and +14 after double-unit CBT (dCBT) by multiparametric flow cytometry analysis, which we term real-time immunophenotyping (RTIP). RTIP analysis at day +14 revealed distinctive patterns of reconstitution and, importantly, identified patients with slow hematopoietic recovery who went on to engraft. Strikingly, higher absolute numbers of circulating monocytes and natural killer cells at day +14 were predictive of engraftment, but only the absolute number of circulating monocytes was significantly correlated with time to engraftment. This is the first evidence that RTIP on patient peripheral blood mononuclear cells early after dCBT is technically feasible and can be used as a "signature" for predicting the kinetics of hematopoietic recovery. Furthermore, RTIP is a time- and cost-efficient methodology that has the potential to become a clinically feasible diagnostic tool to guide therapeutic interventions in high-risk patients; therefore, its utility should be evaluated in a large cohort of patients.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ian
authors.initials: I
authors.lastname: Nicoud
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Joseph
authors.initials: J
authors.lastname: Blake
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: David
authors.initials: D
authors.lastname: Oliver
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Emily
authors.initials: E
authors.lastname: Cox
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Filippo
authors.initials: F
authors.lastname: Milano
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Suzan
authors.initials: S
authors.lastname: Imren
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pediatrics, University of Washington, Seattle, Washington. Electronic address: cdelaney@fredhutch.org.
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D051799:Delayed Graft Function; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D007962:Leukocytes / Q000166:cytology* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
keywords: Cord blood transplant; Delayed engraftment; Engraftment kinetics; Primary graft failure; Real-time immunophenotyping