title: Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation.
abstract: Pretransplant values of serum ferritin, albumin, and peripheral blood counts were previously suggested to provide prognostic information about hematopoietic cell transplantation (HCT) outcomes. Whether these "biomarkers" have prognostic value independent of each other and the HCT-comorbidity index (HCT-CI) is unknown. We analyzed data from 3917 allogeneic HCT recipients at multiple sites in the United States and Italy using multivariate models including each biomarker and the HCT-CI. Data from all sites were then randomly divided into a training set (n = 2352) to develop weights for the relevant biomarkers to be added to the HCT-CI scores and a validation set (n = 1407) to validate an augmented HCT-CI compared with the original index. Multivariate analysis with data from one site showed that ferritin, albumin, and platelets-not neutrophils or hemoglobin-were independently associated with increased nonrelapse mortality (NRM) and decreased overall survival. Findings were validated in data from the other sites. Subsequently, in a training set from all sites, ferritin >2500 mg/dL (hazard ratio [HR], 1.69); albumin 3 to 3.5 g/dL (HR, 1.61) and <3.0 g/dL (HR, 2.27); and platelets 50 to <100,000 (HR, 1.28), 20 to <50,000 (HR, 1.29), and <20,000 (HR, 1.55) were statistically significantly associated with NRM. Weights were assigned to these laboratory values following the same equation used to design the original index. In the validation set, the addition of the biomarkers to the original index to develop an augmented HCT-CI resulted in a statistically significant increase in a higher c-statistic estimate for prediction of NRM (P = .0007). Ferritin, albumin, and platelet counts are important prognostic markers that further refine the discriminative power of the HCT-CI for transplant outcomes.
authors: Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Jennifer E
authors: JE
authors: Vaughn
authors: Clinical Statistics Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors: Barry E
authors: BE
authors: Storer
authors: Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors: Philippe
authors: P
authors: Armand
authors: Department of Hematology, S. Bortolo Hospital, Vicenza, Italy.
authors: Roberto
authors: R
authors: Raimondi
authors: Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors: Christopher
authors: C
authors: Gibson
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Alessandro
authors: A
authors: Rambaldi
authors: Hematology and BMT Unit, San Raffaele Scientific Institute, Milano, Italy.
authors: Fabio
authors: F
authors: Ciceri
authors: Division of Hematology, Ospedale San Martino, Genova, Italy.
authors: Rosi
authors: R
authors: Oneto
authors: Department of Hematology/Oncology, University of Torino, Torino, Italy.
authors: Benedetto
authors: B
authors: Bruno
authors: Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Paul J
authors: PJ
authors: Martin
authors: Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Brenda M
authors: BM
authors: Sandmaier
authors: Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Rainer
authors: R
authors: Storb
authors: Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington. Electronic address: msorror@fhcrc.org.
authors: Mohamed L
authors: ML
authors: Sorror
mesh_terms: D000418:Albumins / Q000378:metabolism*; D015897:Comorbidity; D005293:Ferritins / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D010976:Platelet Count / Q000295:instrumentation*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous / Q000379:methods* / Q000401:mortality; D054928:Validation Studies as Topic
chemical_list: D000418:Albumins; D005293:Ferritins
keywords: Albumin; Biomarkers; Ferritin; HCT-CI; HCT-comorbidity index; Hematopoietic cell transplantation; Platelet count survival