Increasing access to allogeneic hematopoietic cell transplant: an international perspective

Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly complex, costly procedure for patients with oncologic, hematologic, genetic, and immunologic diseases. Demographics and socioeconomic status as well as donor availability and type of health care system are important factors that influence access to and outcomes following allo-HCT. The last decade has seen an increase in the numbers of allo-HCTs and teams all over the world, with no signs of saturation. More than 80 000 procedures are being performed annually, with 1 million allo-HCTs estimated to take place by the end of 2024. Many factors have contributed to this, including increased numbers of eligible patients (older adults with or without comorbidities) and available donors (unrelated and haploidentical), improved supportive care, and decreased early and late post-HCT mortalities. This increase is also directly linked to macro- and microeconomic indicators that affect health care both regionally and globally. Despite this global increase in the number of allo-HCTs and transplant centers, there is an enormous need for increased access to and improved outcomes following allo-HCT in resource-constrained countries. The reduction of poverty, global economic changes, greater access to information, exchange of technologies, and use of artificial intelligence, mobile health, and telehealth are certainly creating unprecedented opportunities to establish collaborations and share experiences and thus increase patient access to allo-HCT. A specific research agenda to address issues of allo-HCT in resource-constrained settings is urgently warranted.

Invasive mold infections in allogeneic hematopoietic cell transplant recipients in 2020: have we made enough progress?

Background Despite progress in diagnostic, prevention and treatment strategies, invasive mold infections (IMI) remain leading cause of mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT-recipients). Methods We describe the incidence, risk factors, and mortality of allo-HCT-recipients with proven/probable IMI in a retrospective single-center 10-year (01.01.2010-01.01.2020) cohort study. Results Among 515 allo-HCT-recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%) and other molds (8/51, 15%). Overall 35/51 (68.6%) breakthrough-IMI (bIMI) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31-180, and >180 days post-HCT, respectively. Risk factors for IMI included: prior allo-HCT (SHR:4.06, p=0.004) and ≥grade-2 acute graft-versus-host disease (aGvHD; SHR: 3.52, p<0.001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI (p=0.02). Mortality predictors included: disease relapse (HR:7.47, p<0.001), aGvHD (HR:1.51, p=0.001), CMV-serology-positive recipients (HR:1.47, p=0.03), and IMI (HR:3.94, p<0.001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (logrank 0.47). At 1-year post-IMI diagnosis, 70.8% (34/48) of patients were dead. Conclusions IA mortality has remained relatively unchanged during the last two decades. More than two thirds of allo-HCT-recipients with IMI die by 1-year post-IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.

Venous Thromboembolism Is Associated with Inferior Survival after Allogeneic Hematopoietic Cell Transplant

Introduction Venous thromboembolism (VTE) is a common complication of both solid and hematologic malignancies. Risk factors for VTE and standard recommendations for prevention and treatment primarily pertain to solid tumor patients. There are fewer data in patients who have undergone allogeneic hematopoietic cell transplant (HCT). Therefore, we studied the incidence, risk factors, and impact of VTE on post-HCT outcomes. Methods We retrospectively reviewed 431 patients who underwent allogeneic HCT between 1/2014 and 8/2019 to identify patients with VTE. VTE was estimated with cumulative incidence methods. Risk factors for VTE were identified with Fine and Gray regression and results are reported as hazard ratio (HR) with a 95% confidence interval (CI). An apriori list of potential risk factors for VTE included age, gender, race, performance status, co-morbidity index, number of prior chemotherapy regimens, history of VTE, disease risk, donor/graft source, transplant conditioning regimen, and acute or chronic graft vs. host disease (GVHD). VTE was analyzed as a time-dependent covariate relative to other post-HCT outcomes. Results Patient characteristics are shown in the Table. The median age at time of transplant was 59 years, (range 18-76); 55.5% were male, the majority (90.7%) were White. The most common indication for transplant was acute myelogenous leukemia and myelodysplastic syndrome (70.3%). Within our cohort, 64 patients (14.8%) developed VTE after allogeneic HCT. The cumulative incidence of VTE at 1 year was 9% (CI 7-12%). Median time to VTE was 9.8 months (range 0.7-74.0) (Figure). Thrombosis site breakdown included the following: lower deep vein thrombosis (DVT) n=47 (74%), catheter related DVT n=12 (19%), DVT and pulmonary embolism (PE) n=12 (19%), PE alone n=4 (6%). Patients were most commonly treated with a direct oral anticoagulant (n=27, 42%), followed by enoxaparin (n=15, 23.4%). The majority of patients (n=38, 58%) were treated with anticoagulation for more than 6 months. Six (9.4%) patients had recurrent thrombosis after completion of anticoagulation therapy from the time of transplant until last known follow-up. Only 9 (14%) had an inferior vena cava filter placed due to contraindications for anticoagulation. In patients treated with anticoagulation, there was a low overall incidence of clinically significant bleeding (n=3, 5%). In multivariable analysis, age (HR 1.36 per 10-year increase, CI 1.09-1.70, P=0.006), history of VTE (HR 1.95, CI 1.09-3.48, P=0.024), and grade 2-4 acute GVHD (HR 1.75, CI 1.05-2.94, P=0.033) were significantly associated with VTE. VTE was not associated with relapse mortality (HR 0.95, CI 0.44-2.04, P=0.89), however VTE was significantly associated with an increased risk of non VTE-associated non-relapse mortality (NRM) (HR 4.09, CI 2.47-6.74, P<0.001) and decreased overall survival (OS) (HR 2.19, CI 1.48-3.24, P<0.001). Discussion VTE is an important complication after allogeneic HCT and is associated with significantly increased NRM and inferior OS. Older patients, those with a prior history of VTE, and patients with acute GVHD are at increased risk for development of VTE after HCT. We found an overall low risk of bleeding with anticoagulation and further study to investigate the role of prophylaxis in this high-risk cohort is needed. Figure 1 Figure 1. Disclosures Sobecks: CareDX: Membership on an entity's Board of Directors or advisory committees. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Angelini: Sanofi: Membership on an entity's Board of Directors or advisory committees. Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees.

202. The Impact and Safety of Discontinuing Routine Surveillance Blood Culture Monitoring in Allogeneic Hematopoietic Cell Transplant Recipients

Background Bloodstream infections (BSI) cause significant morbidity and mortality after hematopoietic cell transplant recipients (HCT). Surveillance blood cultures (SBC) are commonly used to decrease the risk of developing BSI but prior data suggest limited clinical utility. At our center, SBC monitoring was discontinued on 12/1/2019. This is a single center study evaluating the impact and safety of discontinuing routine SBC monitoring. Methods Retrospective review of allogeneic hematopoietic cell transplant recipients (HCTR) seen before (12/1/2017 – 11/30/2019) and after (12/1/2019 - 12/1/2020) discontinuation of SBC. We evaluated utility of SBC and the impact of discontinuation of SBC on admissions, mortality, and other variables. Results One hundred thirty-six and 133 HCTR were followed before and after discontinuation of SBC, respectively. Median (range) ages were 58 (22-73) and 56 (19-73); 60 (44%) and 59 (44%) were female, respectively. The most common cancer was acute myelogenous leukemia (71 (52%) and 61 (46%)); 87 (64%) and 77 (58%) had graft-versus-host disease respectively. Pre-intervention, 1946 SBCs were drawn; 81/1946 (4.2%) were positive. Post-intervention, 29 SBC were drawn; 1/29 (3.4%) were positive. Of the 82 positive SBCs, 63 (77%) were skin flora, and 9 (11%) were gram negative rods. No cultures grew Staphylococcus aureus or fungi. Fifty-one (63%) of the positive SBC resulted in an admission; median (range) length of stay (LOS) was 3 days (1-11). Following discontinuation of SBC, median monthly blood culture-related admissions decreased from 3 (0-6) to 1 (0-3) shown in Figure 1. In the pre-intervention period, there were 2 BSI-related deaths, and 0 following cessation of SBCs. Figure 1. Monthly Hospital Admissions for Positive Outpatient Blood Cultures Conclusion SBCs were infrequently positive and often resulted in unnecessary antibiotic use, admission, and clinical interventions. After SBC monitoring was discontinued, there was a decrease in hospital admissions and health care utilization for positive blood cultures drawn in the outpatient setting. This intervention did not negatively impact clinical outcomes, including BSI-related mortality. Discontinuation of SBC appears to be safe and results in a reduction in healthcare utilization. Centers performing SBC should consider eliminating this practice. Disclosures Ghady Haidar, MD, Karuys (Grant/Research Support)