Background Little is known about characteristics of seasonal human coronavirus (HCoV) (NL63, 229E, OC43 and HKU1) after allogeneic stem cell transplantation (allo-HCT). Patients and methods this is a collaborative Spanish and European bone marrow transplantation groups retrospective multicentre study, which included allo-HCT recipients (adults and children) with upper and/or lower respiratory tract disease (U/LRTD) caused by seasonal HCoV diagnosed through multiplex PCR assays from January 2012 to January 2019. Results We included 402 allo-HCT recipients who developed 449 HCoV U/LRTD episodes. Median age of recipients was 46 years (range 0.3-73.8 years). HCoV episodes were diagnosed at a median of 222 days after transplantation. The most common HCoV subtype was OC43 (n=170, 38%). LRTD involvement occurred in 121 episodes (27%). HCoV infection frequently required hospitalization (18%), oxygen administration (13%) and intensive care unit (ICU) admission (3%). Three-month overall mortality after HCoV detection was 7% in the whole cohort and 16% in those with LRTD. We identified 3 conditions associated with higher mortality in recipients with LRTD: absolute lymphocyte count <0.1 x10 9/mL [hazard ratio (HR), 10.8], corticosteroid (HR 4.68) and ICU admission (HR 8.22) (p<0.01). Conclusions Seasonal HCoV after allo-HCT may involve the LRTD in many instances, leading to a significant morbidity.

3495 Introduction: Hepatic dysfunction is one of the most frequent and less studied complications in the setting of allogeneic stem cell transplantation (Allo). To analyze the incidence, characteristics, risk factors and impact on outcome of hepatic dysfunction in reduced intensity conditioning Allo (Allo-RIC) recipients we conducted a retrospective study in three large Spanish centers. Patients and Methods: We analyzed 452 consecutive patients receiving an Allo-RIC between February 1998 and December 2008. Median age was 53 years (range [rg] 18–71). The median follow-up for survivors was 4 years (rg 0.2–10) RIC consisted in fludarabine 150mg/m2 plus melfalan 70–140 mg/m2 or busulfan 8–10mg/kg. Grades of hepatic dysfunction were defined according to the National Cancer Institute criteria (3.0). Severe hepatic toxicity was considered in patients presenting grade III-IV abnormalities after Allo-RIC in at least one of the following: aspartate aminotransferase (AST), alanine aminotransaminase (ALT), gamma glutamyl transpeptidase (GGT), total bilirubin and protrombin time. Results: A total of 307 patients (68%) developed grade III-IV hepatic toxicity at a median time of 176 days (rg 0–3868) for a cumulative incidence of 69% (95%IC 63–76). A total of 123 (27%), 179 (40%), 140 (31%) and 132 (29%) patients developed grade III-IV levels of AST, ALT, GGT and bilirubin, respectively. Median time of detection of AST, ALT, GGT and bilirubin peaks in days was 177 (rg 0–1200), 168 (rg 0–2253), 452 (rg 257–3126) and 74 (rg 0–783), respectively. Grade III-IV protrombin time abnormalities were found in 23 (5%) patients at a median time of 69 days (11-3868). Main causes of severe hepatic toxicity after Allo were graft versus host disease (GVHD) (n=127, 41%) and pharmacological toxicity (n=32, 10%). In multivariate analysis, risk factors for the development of severe hepatic toxicity were unrelated donors (HR 1.4 [95%CI 1–1.9] p=0.03), use of busulfan in the conditioning regimen (HR 1.3 [95%CI 1–1.7] p=0.04) and high levels of bilirubin and GGT before transplant (HR 2.4 [95%CI 1.6–3.2] p<0.001 and HR 2.7 [95%CI 1.7–4.3] p<0.001, respectively). Patients with severe hepatic toxicity showed higher 4-years non-relapse mortality (NRM) (HR 1.5 [95%CI 1.1–2.1] =0.01) and lower 4-years overall survival (OS) (HR 1.7 [95%CI 1.2–2.5] =0.007). Regarding specific hepatic toxicities, patients with grade III-IV bilirubin levels showed higher NRM and lower OS (HR 3.4 [95%CI 2.3–5.2] p<0.001 and HR 2.5 [95%CI 1.7–3.8] p<0.001, respectively), while patients with grade III-IV protrombin time abnormalities had lower OS (HR 2 [95%CI 1.2–3.4], p=0.005). AST and ALT abnormalities after Allo did not have any impact on NRM and OS. Interestingly, patients with high GGT levels after Allo seemed to have a better outcome with lower NRM and higher OS (HR 0.1 [95%CI 0.1–0.2] p<0.001 and HR 0.2 [95%CI 0.1–0.4] p<0.001, respectively). Regarding GVHD, patients with severe hepatic toxicity did not show higher incidence of acute or chronic GVHD. Conclusion: Hepatic toxicity is frequent and diverse after Allo-RIC. Grade III-IV bilirubin levels were associated with worse outcome of the procedure while grades III-IV GGT levels seemed to be associated with better outcome. High transaminase levels did not show an impact in our patients. Disclosures: No relevant conflicts of interest to declare.

Introduction: Morbidity and mortality after allogeneic hematopoietic stem cell transplantation (AlloHSCT) are considerable, but historically it has been difficult to generate a reproducible and easy model for predicting mortality after the procedure. The use of RIC or nonmyeloablative conditioning regimens may allow an extension of the procedure to patients not eligible for conventional AlloHSCT. However, such patients are usually older and have more comorbidities than patients who meet the strict criteria for a conventional AlloHSCT. In an attempt to predict before transplantation the higher mortality risks attributable to patient comorbidities, researchers from Seattle have recently developed several comorbidity indexes (HCT-CI Blood, 2005 and PAM Ann Int Med, 2006) with the aim of improving non-transplant classical models, such as the Charlson Comorbidity Index (CCI). The validation of these comorbidity indexes in other institutions and in different disease and conditioning-related settings is of utmost importance for the extension of their use to clinical practice and clinical research. We thus performed a retrospective study in our institution to validate these indexes in the setting of RIC AlloHSCT recipients only. Methods: Overall survival (OS) curves were estimated using the Kaplan-Meier method, while the cumulative incidence of non-relapse mortality (NRM) was calculated considering relapse as a competitive event. Likelihood ratio statistics from proportional hazard regression models were computed for each index for the study events over the first two years post-AlloHSCT. The c-statistic was calculated to estimate the predictive capacity of each index for the analyzed transplant outcomes as previously described (Stat Med, 1984). Results: We retrospectively calculated for each patient the HCT-CI, PAM and CCI scores. Study subjects included 194 consecutive patients who underwent RIC-AlloHSCT in our institution up to November 2006, to allow at least 18 months follow-up in all cases. The median age was 57 years (range 17–71). According to the score, three risk groups were created for each index (low, intermediate and high risk). No significant differences were found between the three risk groups of each index regarding age, sex, underlying disease, relapse risk at transplantation and donor type (79% HLA identical sibling donors). The median patient pre-transplant comorbidity scores for CCI, HCT-CI and PAM were 0, 3.5 and 22, respectively. For predicting 2-year NRM, the HCT-CI score groups were associated with the highest predictive hazard ratios (HR) (Low risk, HR 1.0; Intermediate risk, HR, 5.01 [95% C.I., 1.53–16.4]; High risk, 6.97 [95% C.I., 2.20–22.1], p<0.01). However, we found no predictive value for NRM with the risk group categorization using the PAM nor the CCI. The better predictive capacity for NRM of the HCT-CI than PAM and CCI was confirmed with the c-statistics (c-statistics of 0.672, 0.634, 0,595, respectively). Regarding the 2-year OS, the HCT-CI scores categories were also associated with the highest predictive HR (Low risk, HR 1.0; Intermediate risk, HR 1.6 [95% C.I., 0.99–2.72], High risk, 2.7 [95% C.I., 1.66–4.28], p<0.01). In conclusion, our single-center study suggests that the HCT-CI is a good predictor of 2-year NRM and survival after a RIC AlloHSCT, and thus we encourage international efforts to validate and improve this and other predictive indexes.