We analyzed CIBMTR data to evaluate the incidence of non-relapse mortality (NRM) and association with overall survival (OS) for bacterial blood stream infections (BSIs) occurring within 100 days of ...alloHCT in 2 different phases: pre-/peri-engraftment (BSI very early phase, BSI-VEP) and BSI post-engraftment (BSI occurring between 2 weeks after engraftment and day 100, late early phase, BSI-LEP). Of the 7128 alloHCT patients, 2656 (37%) had ≥1 BSI by day 100. BSI-VEP, BSI-LEP, and BSI-Both constituted 56% (n = 1492), 31% (n = 824), and 13% (n = 340) of total BSI, respectively. Starting in 2009, we observed a gradual decline in BSI incidence through 2012 (61-48%). Patients with BSI-VEP were more likely to receive a myeloablative conditioning (MAC) regimen with total body irradiation (TBI). NRM was significantly higher in patients with any BSI (RR 1.82 95% CI 1.63-2.04 for BSI-VEP, RR 2.46, 95% CI 2.05-2.96 for BSI-LEP, and RR 2.29, 95% CI 1.87-2.81 for BSI-Both) compared with those without BSI. OS was significantly lower in patients with any BSI compared with patients without BSI (RR 1.36, 95% CI 1.26-1.47 for BSI-VEP; RR 1.83, 95% CI 1.58-2.12 for BSI-LEP: RR 1.66, 95% CI 1.43-1.94 for BSI-Both). BSIs within day 100 after alloHCT are common and remain a risk factor for mortality.
Summary
Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)‐matched ...allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA‐haploidentical HCT recipients who receive post‐transplant cyclophosphamide (PTCy)‐based graft‐versus‐host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin‐based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment‐related mortality hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13–4⋅07; P = 0⋅002 and inferior 2‐year overall survival (HR 1⋅65, 99% CI 1⋅11–2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long‐term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long‐term outcomes in such patients.
Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier ...injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other).
To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.
A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16 875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 8.8%), MBI-LCBI and BSI-other (698 4.1%), BSI-other only (2928 17.4%), and controls with no BSI (11 768 69.7%). Statistical analysis was performed from April 5 to July 17, 2018.
Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups.
Of the 16 875 patients in the study (9737 57.7% male; median range age, 47 0.04-82 years) 13 686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio HR, 1.21 99% CI, 1.04-1.41), cord blood grafts (HR, 2.89 99% CI, 1.97-4.24), myeloablative conditioning (HR, 1.46 99% CI, 1.19-1.78), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 99% CI, 1.38-2.48). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 99% CI, 1.56-2.12), BSI-other (HR, 1.81 99% CI, 1.60-2.06), and MBI-LCBI plus BSI-other (HR, 2.65 99% CI, 2.17-3.24) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 18.8%), BSI (251 of 1537 16.3%), and MBI-LCBI plus BSI (94 of 435 21.6%) than for controls (566 of 4740 11.9%).
In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population.
Background
There is little longitudinal information about the type and frequency of harm resulting from medication errors among outpatient children with cancer. We aimed to characterize rates and ...types of medication errors and harm to outpatient children with leukemia and lymphoma over 7 months of treatment.
Methods
We recruited children taking medications at home for leukemia or lymphoma from three pediatric cancer centers. Errors were identified by chart review, in‐home medication review, observation of administration, and interviews. Physician reviewers confirmed error (Fleiss' κ = 0.95), harm (Fleiss' κ = 0.82), and suggested interventions. Generalized linear mixed models with random effects were used to account for clustering by site.
Results
Among 131 children taking 1669 medications with 367 home visits, 408 errors were identified, including 242 with potential for harm and 39 with harm (1.0 harm per 1000 patient‐days 95% CI, 0.1–9.8). Ten percent of children were injured by errors and 42% had errors with potential for harm. Twenty‐six percent of caregivers reported that miscommunication led to missed doses or overdoses at home. Children on >13 medications had significantly more serious medication errors than those on fewer medications (77% vs 61%; p = .05). Physician reviewers judged that improved communication among caregivers and between caregivers and clinicians may have prevented the most harm (66%).
Conclusions
In this longitudinal study, 10% children with leukemia or lymphoma experienced adverse drug events because of outpatient medication errors. Improvements addressing communication with and among caregivers should be codeveloped with families and based on human‐factors engineering.
Plain Language Summary
In this longitudinal study, medication errors in the clinic, pharmacy, or at home among children with leukemia or lymphoma over a 7‐month period were common, and 10% suffered harm because of errors.
Children on >13 medications had significantly more serious medication errors than those on fewer medications (77% vs 61%; p = .05).
Physician reviewers judged that improved communication among caregivers and between caregivers and clinicians may have prevented the most harm (66%). Improvements addressing communication with and among caregivers should be codeveloped with families and based on human‐factors engineering.
In this longitudinal study, medication errors in the clinic or at home among children with leukemia or lymphoma over a 7‐month period were common, and 10% suffered from harm from errors. Improvements addressing communication within and among caregivers may have prevented the most harm among the study population.
Post-transplant cyclophosphamide (PTCy) is increasingly used to reduce graft-versus-host disease after hematopoietic cell transplantation (HCT); however, it might be associated with more infections. ...All patients who were ≥2 years old, receiving haploidentical or matched sibling donor (Sib) HCT for acute leukemias or myelodysplastic syndrome, and either calcineurin inhibitor (CNI)- or PTCy-based GVHD prophylaxis Haploidentical HCT with PTCy (HaploCy), 757; Sibling with PTCy (SibCy), 403; Sibling with CNI-based (SibCNI), 1605 were included. Most bacterial infections occurred within the first 100 days; 953 patients (34.5%) had at least 1 infection and 352 patients (13%) had ≥2 infections. Patients receiving PTCy had a greater incidence of bacterial infections by day 180 HaploCy 46%; SibCy 48%; SibCNI 35%; p < 0.001. Compared with the SibCNI without infection cohort, 1.99-fold, 3.33-fold, 2.78-fold, and 2.53-fold increased TRM was seen for the HaploCy cohort without infection and HaploCy, SibCy, and SibCNI cohorts with infection, respectively. Bacterial infections increased mortality HaploCy (HR1.84, 99% CI: 1.45-2.33, p < 0.0001), SibCy cohort (HR,1.68, 99% CI: 1.30-2.19, p < 0.0001), and SibCNI cohort (HR,1.76, 99% CI: 1.43-2.16, p < 0.0001). PTCy was associated with increased bacterial infections regardless of donor, and bacterial infections were associated with increased mortality irrespective of GVHD prophylaxis. Patients receiving PTCy should be monitored carefully for bacterial infections following PTCy.
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