title: Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation.
abstract: Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+)cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+)cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; ≥10.8 × 10(10)cells) was associated with improved overall survival [HR 0.69 (0.54-0.88),P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85),P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85),P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77),P=0.0032]. In contrast, higher doses of CD34(+)cells (top quartile; ≥10.9 × 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+)cell dose.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA, USA psmartin@fhcrc.org.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Martin
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nikiforow
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kekre
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA, USA.
authors.forename: C John
authors.initials: CJ
authors.lastname: Luckey
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D002467:Cell Nucleus / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016179:Granulocyte Colony-Stimulating Factor