Pre-Transplant Ferritin, Albumin and Platelet Count Add Prognostic Information to Comorbidities for Allogeneic Hematopoietic Cell Transplantation (HCT) Outcomes: A Multi-Center Discovery-Validation Study

Abstract

▪Albumin, ferritin, and peripheral blood counts broadly capture health status in patients undergoing allogeneic stem cell transplantation (HCT). Whether they add any prognostic information to the HCT-Comorbidity Index (HCT-CI) is unknown. We analyzed the independent prognostic role of a group of 5 biomarkers (ferritin, albumin, absolute neutrophil count (ANC), hemoglobin (Hgb), and platelet (Plt) count) in pts given allogeneic HCT for hematologic malignancies.This was a multi-center, retrospective discovery-validation study comprising data from 3917 recipients of allogeneic HCT at the Fred Hutchinson Cancer Research Institute (FHCRC) (n=1789) and Dana Farber Cancer Institute (DF) (n=716) in the US and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) (n=1412) in Italy (Table 1). Proportional hazard models were used to estimate the hazards of non-relapse mortality (NRM) and survival after adjustment for the HCT-CI, donor type, CMV serostatus, regimen intensity, age, disease risk and Karnofsky Performance Status (KPS). These were stratified by institution. Model performances were tested by c-statistic estimates.In an initial analysis within the FHCRC population, ANC of <500 and Hgb of < 9 were not associated with outcomes in the models. Alternatively, ferritin >1000 (HR 1.98; p=0.0003) and >2500 (HR 1.97; p=0.0005); albumin <3.5 (HR 1.63; p<0.00001) and <3.0 (HR 1.73 p<0.0001); and Plt <100k (HR 1.65; p<0.0001), <50k (HR 1.52; p<0.0001) , and <20K (HR 1.54; p<0.008) were all statistically significantly associated with NRM.Results were validated in a larger population from DF and GITMO. In multivariate models, adjusted for previously mentioned variables, ferritin >2500 and incremental decreases in albumin and Plt counts had statistically significant associations with both NRM and survival (Table 2). Of note, HCT-CI scores (2, 3 and >4) also retained significant associations with NRM and survival in the presence of the three biomarker values and in both cohorts. Subsequent multivariate analyses stratified the whole cohort (n=3917) into a training (n=2352) and a validation (n=1407) set. In both sets, albumin <3.5, plts <100K, and ferritin >2500 had statistical significance associations with NRM and survival. Each of the three biomarker values were subsequently assigned a weight of 1 following the same equation used to develop the HCT-CI. The augmented HCT-CI/biomarker index had higher c-statistic estimate (0.61) for prediction of NRM compared to the HCT-CI alone (0.58) in the validation set.Ferritin, albumin, and Plt counts are simple and valid prognostic biomarkers for transplant outcomes and should be considered in combination with the HCT-CI in risk assessment prior to allogeneic HCT. The physiology behind these associations warrants further investigation to identify areas of intervention that may improve outcomes.Table 1:Pt characteristicsFHCRC(N=1789)DF/GITMO(N=2128)N (%)N (%)DonorRelated900 (50)1062 (50)Unrelated889 (50)1053 (50)Disease riskLow740 (41)866 (43)High1049 (59)1157 (57)Age< 501025 (57)1120 (53)≥ 50764 (43)1008 (47)ConditioningMA983 (55)1100 (52)RIC/NMA806 (45)1004 (48)Pt CMV-773 (43)505 (24)+1016 (57)1581 (76)KPS≤ 90691 (39)644 (33)90-1001098 (61)1304 (67)Table 2:Multivariate analysis showing the associations between biomarkers and NRM and survival.NRMSurvivalMarkerHR1P1HR1P1FHCRCAlbumin≥3.51.01.0<3.5 - 3.01.440.0021.45<0.0001<3.01.77<0.00011.77<0.0001Unk1.150.381.190.11Plts≥100K1.01.0<100K – 50K1.480.00071.280.003<50K – 20K1.490.0031.370.001<20K1.640.0051.580.0004Unk0.660.470.480.14Ferritin≤10001.01.0>1000 - 25001.600.031.700.0006>25002.080.0011.630.007Unk1.420.031.440.002HCT-CI01.01.011.290.121.310.0221.500.011.420.00132.29<0.00012.04<0.0001≥ 42.94<0.00012.42<0.0001DF/GITMOAlbumin≥3.51.01.0<3.5 - 3.01.600.00011.360.0005<3.02.77<0.00012.18<0.0001Unk1.610.011.110.49Plts≥100K1.01.0<100K – 50K1.080.561.020.85<50K – 20K1.170.281.210.06<20K1.380.041.350.009Unk0.640.100.820.28Ferritin≤10001.01.0>1000 - 25001.110.431.230.02>25001.600.0021.69<0.0001Unk1.130.331.120.19HCT-CI01.01.011.310.051.140.1921.290.101.250.0431.480.0061.460.0001≥ 41.74<0.00011.66<0.0001Unk=Unknown1Adjusted for donor , CMV serostatus , regimen intensity , age , disease risk , KPS ; stratified on institution. DisclosuresNo relevant conflicts of interest to declare.