100-day Mortality Research Articles

Sinusoidal Obstruction Syndrome in Adult Patients with B-Cell Acute Lymphoblastic Leukemia Treated with Inotuzumab Prior to Hematopoietic Stem Cell Transplantation

BACKGROUND: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a potentially life-threatening toxicity observed post allo-HCT, with the reported incidence estimated to be 10-15% and mortality as high as 80% based on the severity (Coppell et al. BBMT 2010). Current management of SOS focusses on minimizing transplant- and patient-related factors. Inotuzumab ozogamicin (InO) is a humanized monoclonal antibody-drug conjugate targeting the CD22 antigen and has proven to be more efficacious than conventional chemotherapy in relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) in the INO-VATE ALL phase 3 trial. However, liver-adverse events were more frequently encountered in the InO group with SOS occurring in 22.8% (n=18) of patients who proceeded to allo-HCT (Kantarjian et al. NEJM 2016). Given the effectiveness of InO as salvage therapy pre-HCT, we aimed to investigate incidence and outcomes of SOS in adult patients with R/R ALL that received InO and proceeded to consolidation with HCT. METHODS: We retrospectively studied adult patients (pts) with R/R B-ALL that received InO as salvage therapy and underwent consolidation with allo-HCT at City of Hope from 2014 to 2022. Graft source was peripheral blood for all patients. All pts. received prophylactic therapy with ursodiol and heparin was added to pts receiving myeloablative conditioning. Diagnosis and severity grading for SOS was in accordance with the revised EBMT criteria (Mohty et al. Bone Marrow Transplantation 2016). All pts. with SOS were treated with defibrotide. Fischer's exact test was used to complete the case-control analysis of patients with SOS vs. those without, and univariable analysis was completed using Cox regression. RESULTS: We identified 47 patients in our study, with 12 pts (25.5%) developing SOS post-HCT. Median time to diagnosis of SOS was 11 days (range: 3-41) and grade was very severe in 50% (n=6), severe in 25% (n=3), and mild in 25% (n=3). All pts. received treatment with defibrotide for median 20.5 days (range: 3-34), with resolution of SOS in 66.7% (n=8) of patients. Mortality from SOS was 33.3% (n=4) within a median of 10 days from diagnosis (range: 3-31), with pts. being graded as very severe (n=3, 75%) or severe (n=1, 25%). The group of pts with SOS compared to those without SOS did not have any significant difference in median duration between last dose of InO and HCT (46 vs. 53 days, P=0.37), myeloablative conditioning regimen (42% vs. 49%, P=0.75), TBI-based preparative regimen (50% vs. 57%, P=0.74), or disease status at transplant >CR1 (83% vs. 68%, P=0.83). There was no significant difference between the groups in lines of therapy prior to InO (P=0.79). Both groups received median 2 cycles of InO (P=0.14) and received InO as last therapy prior to HCT in 67% of patients with SOS and 66% in those patients without SOS (P=1.0). Sirolimus-based GVHD prophylaxis was more common in the SOS group (75% vs. 29%, P<0.01), but there was no difference in peak sirolimus level (P=0.81) or median time to peak sirolimus level (7 vs. 3.5 days, P=0.39) between the two subgroups. On univariable analysis, the use of sirolimus as GVHD prophylaxis was the only variable significant for SOS development, HR=7.50 [95% CI:1.7-33.6, P<0.01]. In the SOS group, the 100-day mortality rate was 33.3% (n=4) with median overall survival (OS) post-SOS of 4.3 months (range: 0.2 - 57.2). In the group without SOS, the 100-day mortality rate was 14.2% (n=5) and median OS post-HCT was 10.7 months (range: 0.52 - 39.6). CONCLUSION: To our knowledge, this is the largest single-center retrospective analysis of R/R ALL patients that received InO as salvage therapy pre-HCT. The incidence of SOS was high, and prompt initiation of defibrotide demonstrated efficacy in treating SOS. Despite the effectiveness of Ino as salvage therapy, the risk of SOS can potentially be mitigated by minimizing risk factors, especially the use of sirolimus-based GVHD prophylaxis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Resistance Mechanisms and Clinical Impact of Resistance to the Third Generation Cephalosporins in Species of Enterobacter cloacae Complex in Taiwan.

Enterobacter cloacae complex (ECC) is ubiquitous in the environment and is an important pathogen causing nosocomial infections. Because routine methods used in clinical laboratories cannot identify species within ECC, the clinical significance of each species within ECC is less known. We applied hsp60 gene sequencing to identify the species/clusters of ECC and detected β-lactamase genes and class 1 integrons with PCR for 184 clinical ECC isolates in Taiwan from 2013 to 2014 to investigate the clinical impact of species within ECC. The four most common clusters were E. hormaechei subsp. steigerwaltii (cluster VIII) (29.9%), E. hormaechei subsp. oharae (cluster VI) (20.1%), E. cloacae subsp. cloacae (cluster XI) (12%), and E. kobei (cluster II) (10.3%). E. hormaechei, which consisted of four clusters (clusters III, VI, VII, and VIII), is the predominant species and accounted for 57.1% of the isolates. The ceftazidime resistance rate was 27.2%, and the ceftriaxone resistance rate was 29.3%. Resistance to third generation cephalosporin was associated with a higher 30-day mortality rate. In total, 5 (2.7%), 24 (13.0%), and 1 (0.5%) isolates carried ESBL, AmpC, and carbapenemase genes, respectively. Class 1 integrons were present in 24.5% of the isolates, and most of the cassettes pertain to antibiotic resistance. Resistance to third generation cephalosporins, multidrug resistance, and class 1 integrons were significantly more in E. hormaechei (clusters III, VI, VII, and VIII) than in the other species. The 30-day mortality rate and 100-day mortality did not differ significantly between patients with E. hormaechei and those with infections with the other species. In conclusion, the distribution of third generation cephalosporin resistance, multidrug resistance, and class 1 integrons were uneven among Enterobacter species. The resistance to third generation cephalosporins possessed significant impact on patient outcome.

Short- and long-term outcome of allogeneic stem cell transplantation in infants: A single-center experience over 20 years.

IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment method for a wide range of malignant and non-malignant diseases. Infants constitute a distinct patient group, especially due to their organ immaturity and differences in drug metabolism. The present paper aims to analyse the short- and long-term outcomes after allo-HSCT in infants.Material and methodsIn the study period, 67 patients under 12 months of age underwent allo-HSCT. This study is a retrospective analysis of patient medical records, in the form of paper and electronic documentation.ResultsThe probability of 5-year OS was 69% and 72% in patients with malignant and non-malignant diseases, respectively. The allo-HSCT from a matched donor was associated with improved OS in comparison to haploidentical donor (0.8 vs. 0.58%, p = 0.0425). The overall incidence of acute graft-vs.-host disease (aGVHD) was 59.3%, and grade III–IV aGVHD was diagnosed in 23% of patients. The 100-day non-relapse mortality (NRM) in the study cohort was 17.9%, while the 5-year NRM was 26.9%. Among the causes of NRM, infections occurred in 83.3% of patients, and aGVHD in 16.3% of individuals. Twenty-two children (32.8%) required hospitalization in the pediatric intensive care unit (PICU). The median length of PICU hospitalization was 6 days (range 1 to 12 days). Late sequelae diagnosed during post-transplant surveillance included ocular disorders in 26.8% of patients, cardiac complications in 4.4%, as well as endocrinopathy with short stature (<3rd percentile) in 37.2% and overt hypothyroidism in 35.4%. In the long-term perspective, 83.3% of survivors were able to attend a regular school.ConclusionsImprovements in unrelated donor availability, and better supportive care resulted in better outcomes. Management of infant allo-HSCT recipients requires the formation of multi-disciplinary specialist teams. In addition, the role of parental empowerment must be acknowledged; for example, in speech therapy and rehabilitation.

Clinical Outcomes of Autologous Hematopoietic Stem Cell Transplant in Multiple Myeloma Patients: A 5-year Experience from a Single Centre in North India.

Swati PabbiIntroduction Multiple myeloma (MM) forms a significant proportion of hematological malignancies. Autologous transplantation continues to be an effective consolidation strategy in resource-restricted settings such as India. Objectives The main objective of the study was to analyze the clinical outcomes of autologous hematopoietic stem cell transplant (HSCT) in MM patients in a single tertiary care center in north India over a period of 5 years. Materials and Methods This retrospective observational study was conducted in a tertiary care center in north India. Data of all MM patients who underwent HSCT between January 2014, and December 2018, were analyzed. The outcome of HSCT was investigated in terms of transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and relapse. PFS and OS were calculated by Kaplan-Meier method and differences between the groups were tested for statistical significance using the two-tailed log-rank test. Life-table method was used for the estimation of survival rate at 1, 3, 5, and 6 years. Results Patient characteristics and survival post-transplant was similar to other published Indian studies. In total, 378 patients were diagnosed with MM in our hospital between 2014 and 2018. One hundred ninety-three patients were found to be eligible for autologous HSCT, out of which 52 ended up having a transplant giving us a high percentage (26.9%) of patients receiving a transplant in our setting. Transplant-related mortality (TRM) was nil in the present study. The mean PFS and OS were 62.8 and 70.1 months, respectively. The mean PFS and OS rates at 5 years were 75.3% and 84.2%, respectively. The average cost estimate of HSCT in our setting was 7.2 lakh Indian national rupees. Conclusion Autologous HSCT is a safe procedure with nil 100-day mortality in present series. Moreover, considering the cost of novel agents, autologous transplant remains a cost-effective way for prolonging remission and time-to-next treatment in India.

Real‐world effectiveness of antifungal prophylaxis with posaconazole as the primary agent in patients with haematological malignancies

Patients undergoing induction/reinduction chemotherapy for haematologic malignancies (HM) are at risk for invasive fungal infections (IFIs). In 2015, Duke University Hospital (DUH) implemented a new standardised fungal prophylaxis protocol for adult patients undergoing induction chemotherapy for acute lymphocytic leukaemia, acute myelocytic leukaemia and myelodysplastic syndrome. This study assessed the impact of protocol implementation on (1) use of antifungal prophylaxis, throughout the at-risk period and (2) patient outcomes such as IFI and mortality. Retrospective, observational study of adult HM patients admitted to DUH for induction/reinduction chemotherapy pre- (7/1/2013-12/31/2014) and post- (1/1/2015-10/31/2016) implementation of standardised antifungal prophylaxis protocol (which recommended posaconazole as the first-line agent). Patients were followed for up to 100 days after initiation of induction chemotherapy to evaluate use of antifungal prophylaxis and patient outcomes. 218 patients with haematologic malignancies were included (90 pre, 128 post). Use of antifungal prophylaxis increased from 81.1% (pre) to 97.7% (post) (p < .0001). Overall, 71% received posaconazole as initial antifungal prophylaxis (64.4% pre, 75.7% post). Approximately one-fourth of patients (25.6%, pre vs 26.6%, post) developed an IFI (proven/probable or possible using modified EORTC definitions) (p=.868); 100-day mortality remained stable (18.9% pre vs 18.8% post, respectively, p=.979). Lack of antifungal prophylaxis and older age (≥60 years) were associated with higher risk of IFI. Implementation of a standardised protocol with posaconazole as the primary agent was associated with increased use of antifungal prophylaxis among patients undergoing induction/reinduction chemotherapy for haematologic malignancies in our hospital. Lack of antifungal prophylaxis was an independent predictor of IFIs, underscoring the importance of prophylaxis in this at-risk population.

Predictors of hematologic response and survival with stem cell transplantation in AL amyloidosis: A 25-year longitudinal study.

High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow-up interval of 8 years, the median event-free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1ng/mL, and serum creatinine >2.0mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low-risk (0 factors), intermediate-risk (1 factor), and high-risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p< .001). The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.

P1369: PRETRANSPLANT MODIFIED ENDOTHELIAL ACTIVATION AND STRESS INDEX (M-EASIX-7): A PREDICTOR OF PROGNOSIS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Background: Endothelial damage is considered to be the major underlying mechanism in the physiopathogenesis of transplant related complications including graft versus host disease (GVHD), thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS) and sepsis. A novel scoring index, Endothelial Activation and Stress Index (EASIX), is a simple method consisting of endothelial activation parameters, which was indicated to predict GVHD and posttransplant survival. Similarly, modified EASIX (mEASIX) is a marker of endothelial dysfunction and has been shown to be associated with the development of cytokine release syndrome after CAR-T cell therapy. Aims: In this study, we investigated the role of EASIX and mEASIX scores in the prediction of transplant related complications and survival in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). Methods: A total of 398 alloHCT recipients [median age: 43(17-71) years; male/female: 243/155] were included in this retrospective study. EASIX [lactate dehydrogenase (U/L) x creatinine (mg/dl) / platelets (109/L)] and mEASIX [lactate dehydrogenase (U/L) x C reactive protein (CRP) (mg/dl) / platelets (109/L)] scores were calculated on days -7, 0, +3 and +7. Statistical analysis was performed based on log2 transformed values. Patient and transplant characteristics are summarized in Table 1. Results: Median follow-up time was 573.5 (4-3877) days. Probability of OS was estimated to be 35.1% (1343 ± 351.7; 95% CI: 653.6-2032.3), while the probabilities of day-30 mortality, day-100 mortality and NRM were 6%, 12.5% and 49% respectively. In multivariate analysis EBMT score (p=0.026, HR: 1.177; 95% CI: 1.019-1.359), CRP (p=0.033, HR: 1.004; 95% CI: 1.000-1.008), EASIX-7 (p=0.042, HR: 0.182; 95% CI: 0.035-0.941) and mEASIX-7 (p=0.016, HR: 2.668; 95% CI: 1.202-5.924) were found to have significant impact on OS. The predictive effect of mEASIX-7 was confirmed for day-30 mortality (p=0.038; HR: 1.7; 95% CI: 1.030-2.805). A positive correlation was demonstrated between mEASIX-7 and SOS (p=0.013; r=0.249). On the other hand, mEASIX+7 was found to have a significant impact on the development of engraftment syndrome (p=0.028; HR: 1.403; 95% CI: 1.038-1.896), EASIX+3 on TMA (p=0.027; HR: 2.361; 95% CI: 1.100-5.066) and mEASIX0 on TMA (p=0.011; HR: 2.209; 95% CI: 1.199-4.068). Based on the optimal cutoff value of mEASIX-7 for the prediction of day-30 mortality, which was determined to be 2.71 [AUC: 0.747 (0.599-0.896);p=0.021], the study group was divided into two subgroups as low-mEASIX-7 and high-mEASIX7 groups. Probability of OS was significantly higher in the low-mEASIX-7 group compared to high-mEASIX-7 group (37% vs 25.2%; p=0.008; HR: 2.057; 95% CI: 1.208-3.504). Day-30 mortality (2.9% vs 19.4%; p=0.017; HR: 7.028; 95% CI: 1.418-34.836) and day-100 mortality (9% vs 33%; p=0.004; HR: 4.469; 95% CI: 1.619-12.336) were significantly lower in the low-mEASIX-7 group. Furthermore, the probability of NRM was significantly lower in the low-mEASIX-7 group compared to high-mEASIX-7 group (44.8% vs 61.4%; p=0.005; HR: 2.551; 95% CI: 1.318-4.941). Image:Summary/Conclusion: Pretransplant risk assessment is essential to guide the mainstays of the transplant procedure and optimize supportive care measures. In consideration with the basic role of endothelial activation in the development of life threatening complications of alloHCT, mEASIX-7 is indicated to have a predictive prognostic impact on survival and transplant related complications.

Long-Term Outcomes and Safety Trends of Autologous Stem-Cell Transplantation in Non-Hodgkin Lymphoma: A Report From A Tertiary Care Center in India.

PURPOSEPublished experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India.PATIENTS AND METHODSWe retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B).RESULTSOverall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT.CONCLUSIONIt is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.

The Clinical Value of Procalcitonin in the Neutropenic Period After Allogeneic Hematopoietic Stem Cell Transplantation.

The diagnostic value of procalcitonin and the prognostic role of PCT clearance remain unclear in neutropenic period after allogeneic hematopoietic stem cell transplantation introduction. This study evaluated 219 febrile neutropenic patients (116, retrospectively; 103, prospectively) who underwent allo-HSCT from April 2014 to March 2016. The area under the receiver operator characteristic curve (AUC) of PCT for detecting documented infection (DI) was 0.637, and that of bloodstream infection (BSI) was 0.811. In multivariate analysis, the inability to decrease PCT by more than 80% within 5–7 days after the onset of fever independently predicted poor 100-day survival following allo-HSCT (P = 0.036). Furthermore, the prognostic nomogram combining PCTc and clinical parameters showed a stable predictive performance, supported by the C-index of 0.808 and AUC of 0.813 in the primary cohort, and C-index of 0.691 and AUC of 0.697 in the validation cohort. This study demonstrated the diagnostic role of PCT in documented and bloodstream infection during the neutropenic period after allo-HSCT. PCTc might serve as a predictive indicator of post-HSCT 100-day mortality. A nomogram based on PCTc and several clinical factors effectively predicted the 100-day survival of febrile patients and may help physicians identify high-risk patients in the post-HSCT neutropenic period.

Nivolumab as a bridge to allogeneic hematopoietic stem cell transplantation is associated with improved survival.

The aim of the present study was to compare the effects of nivolumab bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT) on progression-free survival (PFS) and overall survival (OS) and toxicity profile. The study population consisted of relapsed/refractory cases of HL, who were treated with nivolumab for disease control and subsequently underwent allo-SCT at our institution. The control group consisted of HL patients who relapsed or refractory after multiple lines of therapy and underwent allo-SCT without nivolumab before transplantation as bridging therapy. The incidence of acute and chronic graft vs. host disease (GVHD) was similar in both groups. The 100-day mortality occurred in 1 patient (10%) in the nivolumab group and 4 patients (16.7%) in the control group (p = 0.54). During 30-month follow-up, PFS was achieved in 60% of patients in the nivolumab group and 45.8% in the control group (p = 0.69). OS during 30-month follow-up was 80% in the nivolumab group and 41.7% in the control group, OS was superior in patients in the nivolumab group than in the control group (p = 0.04). Allo-SCT after bridging therapy with nivolumab provides a survival advantage over patients who underwent allo-SCT without the bridging. Therapy with nivolumab in combination with post-transplant cyclophosphamide does not appear to increase GVHD.

Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem-Nonsusceptible Enterobacter cloacae Complex Infections in a Taiwan University Hospital.

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an emerging threat to public health but there is still a lack of comprehensive molecular and clinical epidemiological analysis. A total of 157 CnsECC isolates were recovered during October 2011 to August 2017. hsp60 gene sequencing and pulsed-field gel electrophoresis (PFGE) were applied to discriminate the species, genetic clusters and clonal relatedness. All the isolates were subjected to polymerase chain reaction (PCR) analysis for carbapenemase, AmpC-type β-lactamase, and extended spectrum β-lactamase (ESBL) genes. Clinical data were collected on all patients for comparing clinical risks and outcomes between patients with carbapenemase-producing (CP)-CnsECC compared with non-CP-CnsECC infection. The most commonly identified species was E. hormaechei subsp. hoffmannii (47.1%), followed by E. hormaechei subsp. steigerwaltii (24.8%). Different species of CnsECC isolates showed heterogeneity in resistance patterns to piperacillin/tazobactam, cefepime and levofloxacin. In the present study, we observed that E. hormaechei subsp. hoffmannii was characterized with higher cefepime and levofloxacin resistance rate but lower piperacillin/tazobactam resistance rate relative to other species of CnsECC. CP-CnsECC comprised 41.1% (65 isolates) and all of these isolates carried IMP-8. In this study, 98% of patients had antimicrobial therapy prior to culture, with a total of 57/150 (38%) patients being exposed to carbapenems. Chronic pulmonary disease (OR: 2.51, 95% CI: 1.25–5.06), received ventilator support (OR: 5.54, 95% CI: 2.25–12.03), steroid exposure (OR: 3.88, 95% CI: 1.91–7.88) and carbapenems exposure (OR: 2.17, 95% CI: 1.10–4.25) were considered risk factors associated with CP-CnsECC infection. The results suggest that CP-CnsECC are associated with poorer outcomes including in-hospital mortality, 30-day mortality and 100-day mortality. Our study provides insights into the epidemic potential of IMP-8-producing E. cloacae for healthcare-associated infections and underscores the importance of understanding underlying resistance mechanisms of CnsECC to direct antibiotic treatment decisions.

Treatment outcome and efficacy of therapeutic plasma exchange for transplant-associated thrombotic microangiopathy in a large real-world cohort study.

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.

930. Clinically Significant CMV Infections in Patients with Lymphoma or Multiple Myeloma

Abstract Background Clinically significant CMV infections (CS-CMVi) among patients with lymphoma and multiple myeloma (MM) have not been clearly defined, especially considering the new cancer therapies that have revolutionized cancer outcomes of these patients. This study aims at describing clinical outcomes of CS-CMVi in this patient population and identify risk factors for CS-CMVi. Methods This is a single-center, cohort study of all patients with lymphoma and MM who developed CS-CMVi between January 2017 and October 2020. Data was collected from the electronic medical records. CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 26 using a logistic regression model for multivariate analysis. Results We identified 84 patients; 60 (71%) had lymphoma and 24 (29%) had MM (Table 1). CMV end organ disease was diagnosed in 53 (63%) patients as the initial CMV episode and the most common site was the lungs (68%). In our cohort, 25 (30%) patients had autologous HCT and 14 (17%) had CAR T cells infusions prior to CS-CMVi. Recurrent CS-CMVi occurred in 16 (19%) patients (Table 2). A 100-day all-cause mortality was 55%, at a median of 76 days (range 3 -1330 days) after the initial episode of CS-CMVi. CMV related mortality was 11% amongst patients with end organ disease. In multivariate analysis, female gender was associated with a higher risk of CMV end organ disease (OR 3.42, 95% CI 1.14-10.3) and MM with a lower risk of CMV end organ disease compared to lymphoma (OR 0.27, 95% CI 0.07-0.97) (Table 3). Interestingly, 16 (19%) patients received letermovir as secondary prophylaxis for a median of 94 days (range 5 to 339 days) and only 1 patient had recurrent CS-CMVi while on letermovir. Conclusion CS-CMVi, particularly end organ disease, are not uncommon among patients with lymphoma or MM. Routine CMV surveillance and the use of letermovir for secondary prophylaxis in this patient population should be evaluated in further studies. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support)

Ruxolitinib as front-line therapy in graft versus host disease: Efficacy and safety in children

BackgroundRuxolinitib has been used as an effective salvage agent in steroid refractory acute and chronic graft versus host disease (GVHD). We aimed to analyze data on ruxolitinib as front-line therapy in children. Patients and methodsWe included children up to 18 years of age who underwent hematopoietic stem cell transplantation (HSCT), from December 2017 to April 2020, where ruxolitinib was administered in children up to 18 years of age, at 48 hours of diagnosis with acute and within two weeks in chronic GVHD. The dose was 2.5 mg and 5 mg twice daily for children weighing <15 kg and >15 kg respectively. ResultsA total of 80 out of 335 transplanted children were included. The indication was acute GVHD (aGVHD) in 41 and chronic GVHD (cGVHD) in 39 children. Response rates were 90% in aGVHD, with 92% in skin and 46% in acute gut GVHD. Overall response rate in cGVHD was 74.3%, with 80%, 67% and 100% in skin, lung and liver respectively. Thrombocytopenia was the predominant drug related side effect, noted in 65% children. Three children needed drug withdrawal, two due to uncontrolled hyponatremia in aGVHD, and one due to nephrotic syndrome in the cGVHD setting. The 100-day mortality in the historical cohort (January 2014 to October 2017) was 29/279 (10.4%) versus 17/335 (5%) in the study cohort (p = 0.029). ConclusionRuxolitinib used early in acute and chronic GVHD results in excellent response rates and is safe to use in children.

Implementation of a clinical decision rule for selecting empiric treatment for invasive aspergillosis in a setting with high triazole resistance.

World-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric combination therapy with both a triazole and liposomal amphotericin B (LAmB) can be considered because of the low yields of susceptibility testing. To avoid toxicity while optimizing outcome, a strategy with monotherapy would be preferable. A newly designed treatment algorithm based on literature and expert consensus provided guidance for empiric monotherapy with either voriconazole or LAmB. Over a four and a half year period, all adult patients in our hospital treated for IA were included and patient data were collected. An independent committee reviewed the attributability of death to IA for each patient. Primary outcomes were 30- and 100-day crude mortality and attributable mortality. In total, 110 patients were treated according to the treatment algorithm. Fifty-six patients (51%) were initially treated with voriconazole and 54 patients (49%) with LAmB. Combined attributable and contributable mortality was 13% within 30 days and 20% within 100 days. Treatment switch to LAmB was made in 24/56 (43%) of patients who were initially treated with voriconazole. Combined contributable and attributable 100-day mortality in this subgroup was 21% and was not increased when compared with patients initially treated with LAmB (P = 0.38). By applying a comprehensive clinical decision algorithm, an antifungal-sparing regime was successfully introduced. Further research is warranted to explore antifungal treatment strategies that account for triazole-resistance.Lay summaryDue to resistance of Aspergillus against triazoles, combination therapy with liposomal amphotericin B (LAmB) is applied more often as primary therapy against invasive aspergillosis. This study presents the results of a decision tool which differentiated between triazole or LAmB monotherapy.

De-Escalation of Ptcy Dosing in Matched Allogenic Transplants: A Single Institution Retrospective Study

IntroductionThe role of post-transplant cyclophosphamide (PTCy) in preventing acute GVHD (aGVHD) and chronic GVHD (cGVHD) has been well established in the haploidentical setting (Al-Homsi AS et al., Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(4):604-611). More recently, several studies are also supporting its use in matched related and unrelated donors (Williams L et al., Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation. Front Immunol. 2020;11(April):1-7). But as new emerging data are starting to show some toxicities from that regimen, a reevaluation of the optimal PTCy dose is highly valuable (Duléry R et al., Early Cardiac Toxicity Associated with Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation. JACC CardioOncology. 2021;3(2):250-259; Goldsmith et al., Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137(23):3291-3305).PTCy dose de-escalation in preventing GvHD was also evaluated in a phase I/II study (NCT03983850) with initial results indicating that de-escalation of PTCy (DL2, 25 mg/kg/day given in Days 3−4) may provide a feasible and effective approach in preventing severe aGvHD(McAdams MJ et al., Phase I Study De-Intensifying Exposure of Post-Transplantation Cyclophosphamide (PTCy) after HLA-Haploidentical Hematopoietic Cell Transplantation (HCT) for Hematologic Malignancies. Transplant Cell Ther Off Publ Am Soc Transplant Cell Ther. 2021;27(3): S9-S11). However, this was in the setting of haplo-identical transplants. Currently there are no studies that investigate the safety and efficacy of a lower dose of PTCy in matched allogenic transplants.MethodsWe retrospectively selected 37 consecutive patients who underwent transplant at our center from January 2017 to April 2021. Patients who received a mismatched or haploidentical transplants were excluded. 26 matched sibling or matched unrelated donor transplants were further analyzed. These were divided into 3 cohorts according to GVHD prophylaxis: cohort 1 (No-PTCy) received standard calcineurin inhibitor-methotrexate based GVHD prophylaxis (n=16), cohort 2 (PTCy-50) received PTCy at 50 mg/kg (D+3 and D+4) in combination other immunosuppressive drugs (ISD) (n=6), and cohort 3 (PTCy-25) received PTCy at 25 mg/kg (D+3 and D+4) in combination with other ISD (n=4). The reduced PTCy dosing was based on physician discretion due to various reasons (2 cardiac risk, 1 heavy pre-treatment, 1 unknown).ResultsBaseline characteristics are summarized in table 1. Median follow up for all survivors was 523 days (range, 97-1463) while it was shorter for PTCy cohorts at 152 days (97-534). There were zero grade 3 aGVHD in PTCy groups compared to 12.5% (2/16) in No-PTCy cohort (p=0.30). cGVHD was significantly lower in PTCy-50 and PTCy-25 as compared to No-PTCy (0/6, 0/4, 5/16 respectively, p=0.04). The 100-day treatment-related mortality (TRM) was significantly lower in PTCy-25 as compared to PTCy-50 and No-PTCy (0/4, 2/6, 2/16 respectively, p<0.001). There was no viral reactivation (EBV/CMV) in PTCy-25 as compared to 1/6 in PTCy-50 and 5/16 in No-PTCy (p=0.54). The length of hospital stay (LOS) for transplant and the median days for neutrophil recovery (NR) were shorter in PTCy-25 as compared to PTCy-50 and No-PTCy (25.5 days, 31 days and 28.5 days respectively for LOS, p=0.60; 15.5 days, 22 days and 17.5 days for NR, p=0.87). Although the overall survival (OS) seems to favor PTCy-25 (Figure 1), it is limited by short follow up.ConclusionDe-escalating the dose of PTCy to 25mg/kg x 2 in GVHD prophylaxis regimens appears to be efficacious and safe in patients receiving matched allogenic transplant. Further prospective studies including a larger patient sample and longer follow-up is warranted to investigate lower PTCy dosing in matched transplants over the current standard dosing. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Randomized Open Label Pilot Study of Clostridium Butyricum Miyairi 588 (CBM588) in Recipients of Allogeneic Hematopoietic Cell Transplantation

A Randomized Open Label Pilot Study of Clostridium Butyricum Miyairi 588 (CBM588) in Recipients of Allogeneic Hematopoietic Cell Transplantation

Ten-Day Decitabine with Venetoclax (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome: Updated Results of a Phase II Trial

Ten-Day Decitabine with Venetoclax (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome: Updated Results of a Phase II Trial

Improvement in Outcomes of Autologous Stem Cell Transplant in Patients with Lymphoma Older Than 70 Years: The Significance of Age in 2020s?

Backgrounds: Autologous stem cell transplant (ASCT) has been the standard treatment approach for patients with relapsed or high-risk lymphoma for several decades. Despite the improvement in supportive care, age has remained one of the critical factors that determines transplant eligibility and outcomes. Herein, we explored the transplant-related outcomes of patients with lymphoma aged 70 years or older at our institution and compared to those with younger ages.Methods: In this retrospective single center study, we include all patients with diagnosis of lymphoma who underwent ASCT between January 2000 and February 2021 at Mayo Clinic, Rochester, Minnesota. In addition to data obtained from the transplant database, we abstracted data from electronic medical record. We described relevant clinical characteristics and transplant associated outcomes including engraftment, transplant related mortality, relapse incidence, and survival outcomes. We compared the key transplant related outcomes with patients at the younger age group between 65 and 70 years old.Results: A total of 196 patients with lymphoma aged 70 years or older underwent ASCT between January 2000 and February 2021. The median age of patients at the time of ASCT was 72.4 (70.0-78.7) years with 24 patients (12.2%) being older than 75 years old. Of 196 patients, 76 (38.8%) had Charlson comorbidity index of 3 or higher and 10 (5.1%) had performance status of 2 or higher at the time of ASCT. Table 1 summarizes the relevant baseline clinical characteristics of 196 patients in this cohort including the comparison with younger patients (age 65-70 years old, n=296). The most common transplant indication in this cohort was relapsed diffuse large B cell lymphoma. The majority of patients (91.3%) received peripheral blood graft with a median CD34+ cell dose of 5.14x10 6 cells/kg which was significantly lower than younger patients (P=0.01). The rate of neutrophil and platelet engraftment was 99.0% and 98.8% with corresponding median time to engraftment of 13 days for both cell lineages. The 30- and 100-day non-relapse mortality (NRM) of the entire cohort was 1.5% (95%CI 0-3.2%) and 4.6% (95%CI 1.6-7.5%) not statistically different between 70-75 years old and 75 years or older cohorts. With the median follow-up duration of 48 months, the 2-year event free survival (EFS) and overall survival (OS) was 55.9% (95%CI 49.2-63.5%) and 67.4% (95%CI 61.0-74.5%), respectively. Patients from the 70 years old or older cohort had similar EFS but inferior OS compared to the 65-70 years old cohort. However, there was no difference in EFS and OS between 70-75 and >75 years old cohorts. There was overall an improved trend of 30-day NRM, 2-year EFS and 2-year OS over the 3 different transplant periods (Figures). Although not statistically significant, patients who underwent ASCT between 2000 and 2006 had a trend towards higher 30-day NRM compared to patients who were transplanted at later time points (7.3% vs 0%, P=0.06). The major causes of death included progressive lymphoma, infection, and conditioning regimen related organ toxicities.Conclusion: Outcomes of ASCT in older patients with lymphoma have improved over time with an excellent 30-day NRM (0%) in the past recent years. The major cause of treatment failure after ASCT was progressive disease. With appropriate patient selection, ASCT in older patients is feasible and provides acceptable outcomes comparable to the patients from younger age group. [Display omitted] DisclosuresPaludo: Karyopharm: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding.

Outcomes of Aggressive B Cell Lymphoma Patients with No Evidence of Measurable Disease at the Time of CD19 Chimeric Antigen Receptor T Cell Therapy: The Experience from the CAR T Cell Consortium

Outcomes of Aggressive B Cell Lymphoma Patients with No Evidence of Measurable Disease at the Time of CD19 Chimeric Antigen Receptor T Cell Therapy: The Experience from the CAR T Cell Consortium