Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P 2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT

Isavuconazole prophylaxis against invasive fungal infections in allogeneic stem cell transplantation: a single-center experience

Patients undergoing allogeneic stem cell transplantation (alloHCT) require profound immunosuppression is required to preserve graft function and prevent graft-versus host disease (GVHD), resulting in a high risk of infectious complications such as invasive fungal diseases (IFIs). Posaconazole is approved for primary antifungal prophylaxis alloHCT. However, posaconazole is associated with drug-drug interactions which may lead to relevant toxicities limiting it uses in hematological patients. Other triazoles, amphotericine B, and echinocandins can be used in patients at high risk of IFIs. However, there is less evidence supporting the efficacy of these drugs for the prevention of IFIs

The direct and indirect effects of COVID‐19 pandemic in a real‐life hematological setting

Background: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. Aims: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. Methods and results: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). Conclusion: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience

Allo-SCT is a curative option for selected patients with relapsed/refractory (R/R) MCL, but with significant NRM. We present the long-term results of patients receiving allo-SCT in Spain from March 1995 to February 2020. The primary endpoints were EFS, OS, and cumulative incidence (CI) of NRM, relapse, and GVHD. We included 135 patients, most (85%) receiving RIC. After a median follow-up of 68 months, 5-year EFS and OS were 47 and 50%, respectively. Overall and CR rates were 86 and 80%. The CI of relapse at 1 and 3 years were 7 and 12%. NRM at day 100 and 1 year were 17 and 32%. Previous ASCT and Grade 3-4 aGVHD were associated with a higher NRM. Grade 3-4 aGVHD, donor type (mismatch non-related), and the time-period 2006-2020 were independently related to worse EFS. Patients from 1995-2005 were younger, most from HLA-identical sibling donors, and were pretreated less. Our data confirmed that allo-SCT may be a curative option in R/R MCL with low a CI of relapse, although NRM is still high, being mainly secondary to aGVHD. The arrival of new, highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegate allo-SCT to those fit patients who fail these therapies, far away from the optimal timing of treatment

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Applicability and validation of different prognostic scores in allogeneic hematopoietic cell transplant (HCT) in the post-transplant cyclophosphamide era

We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)]. The discriminative capacity of DRI and HCT-CI increased during the post-transplant period, with a peak of prediction at 2 years (AUC of 61.1 % and 61.8 %). The maximum rPAM discriminative capacity was at 1 year (1-year AUC of 58.2 %). The predictive capacity of the EBMT score was not demonstrated. This study validates the discrimination capacity for OS prediction of KPS, HCT-CI, DRI and EASIX in PTCy-based allo-HCT

Easix Score Correlates With Endothelial Dysfunction Biomarkers and Predicts Risk of Acute Graft-Versus-Host Disease After Allogeneic Transplantation

Plasma biomarkers of endothelial dysfunction have been postulated for the diagnosis and prognosis of acute graft-versus-host disease (aGVHD). However, their use is not validated in clinical practice yet. The endothelial activation and stress index (EASIX), a simple score based on routine laboratory parameters, is considered to be an indirect marker of endothelial damage. High value of EASIX was correlated with worse non-relapse mortality (NRM) and overall survival (OS) and a high risk of sinusoidal obstructive syndrome (SOS) and transplant-associated thrombotic microangiopathy (TA-TMA).This study investigates the predictive value of plasma biomarkers and the EASIX score for the prediction of aGVHD.We assessed VCAM-1, TNFR1, and VWF:Ag plasma levels, and EASIX score before allogeneic hematopoietic stem cell transplantation (allo-HSCT), and on days 0, +3, +7, +14, and +21 in an experimental cohort (n=33). EASIX was transformed to a base-2 logarithm to perform the analysis. For the most relevant biomarkers, we estimate the optimal cut-off values and the discriminatory ability to differentiate patients with high-risk of aGVHD. The conclusions obtained in the experimental cohort were validated in a large cohort of 321 patients at the same institution.Plasma biomarkers and EASIX showed similar post-transplant dynamics consisting of a progressive increase. Multivariate analysis showed an association between high TNFR1 levels and Log-2 EASIX score on day +7 post-transplant with an increased likelihood of developing aGVHD (HR 1, P=0.002; HR 2.31, P=0.013, respectively). Patients with TNFR1 ≥1300 ng/mL (HR 7.19, P=0.006) and Log2-EASIX ≥3 (HR 14.7, P<0.001) at day +7 post-transplant were more likely to develop aGVHD with high predictive accuracy (C-index of 74% and 81%, respectively). In the validation cohort, patients with Log2-EASIX ≥ 3 on day +7 post-transplant presented a significantly higher incidence of grade II-IV aGVHD (HR 1.94, P=0.004) independent of GVHD prophylaxis (HR 0.38, P=0.004), conditioning regimen (HR 0.59, P=0.02) and type of donor (HR 2.38, P=0.014).Differential degree of endothelial damage can be measured using both EASIX score and plasma biomarkers in the early post-transplant period. Patients at risk of developing aGVHD could be easily identified by a high EASIX score. Both indicators of endothelial activation represent a promising approach to predict aGVHD.Published by Elsevier Inc