title: Absolute lymphocyte count recovery after allogeneic hematopoietic stem cell transplantation predicts clinical outcome.
abstract: Immune reconstitution is critical for clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). To determine the impact of absolute lymphocyte count (ALC) recovery on clinical outcomes, we conducted a retrospective study of 1109 adult patients who underwent a first allogeneic HSCT from 2003 through 2009, excluding patients who died or relapsed before day 30. The median age was 51 years (range, 18 to 74) with 52% undergoing reduced-intensity conditioning and 48% undergoing myeloablative conditioning HSCT with T cell-replete peripheral blood stem cells (93.7%) or marrow (6.4%) grafts. The median follow-up time was 6 years. To determine the threshold value of ALC for survival, the entire cohort was randomly split into a training set and a validation set in a 1:1 ratio, and then a restricted cubic spline smoothing method was applied to obtain relative hazard estimates of the relationship between ALC at 1 month and log hazard of progression-free survival (PFS). Based on this approach, ALC was categorized as ≤.2 × 10(9) cells/L (low) or >.2 × 10(9) cells/L. For patients with low ALC at 1, 2, or 3 months after HSCT, the overall survival (OS) (P ≤ .0001) and PFS (P ≤ .0002) were significantly lower and nonrelapse mortality (NRM) (P ≤ .002) was significantly higher compared with patients with ALC > .2 × 10(9) cells/L at each time point. When patients who had low ALC at 1, 2, or 3 months after HSCT were grouped together and compared, their outcomes were inferior to those of patients who had ALC > .2 × 10(9) cells/L at 1, 2, and 3 months after HSCT: the 5-year OS for patients with low ALC was 28% versus 46% for patients with ALC > .2 × 10(9) cells/L, P < .0001; the 5-year PFS was 21% versus 39%, P < .0001, respectively and 5-year NRM was 40% versus 18%, P < .0001, respectively. This result remained consistent when other prognostic factors, including occurrence of grade II to IV acute graft-versus-host disease (GVHD), were adjusted for in multivariable Cox models stratified by conditioning intensity: hazard ratio (HR) for OS: 1.52; P ≤ .0001; for PFS: 1.42; P = .0008; and for NRM: 2.4 P < .0001 for patients with low ALC. Low ALC was not significantly associated with relapse (HR, 1.01; P = .92) in the multivariable model. Low ALC early after HSCT is an independent risk factor for increased NRM and poor survival independent of grade II to IV acute GVHD.
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: kim.haesook@jimmy.harvard.edu.
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Frederick
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Emily
authors.initials: E
authors.lastname: Andler
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Department of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020127:Recovery of Function; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning
keywords: Absolute lymphocyte count (ALC); Hematopoietic stem cell transplantation (HSCT); Lymphocyte