Allogeneic hematopoietic cell transplantation is indicated for refractory hematologic cancer and some nonmalignant disorders. Survival is limited by recurrent cancer and organ toxicity.
To determine ...whether survival has improved over the past decade and note impediments to better outcomes.
The authors compared cohorts that had transplants during 2003 to 2007 versus 2013 to 2017. Survival outcome measures were analyzed, along with transplant-related complications.
A center performing allogeneic transplant procedures.
All recipients of a first allogeneic transplant during 2003 to 2007 and 2013 to 2017.
Patients received a conditioning regimen, infusion of donor hematopoietic cells, then immunosuppressive drugs and antimicrobial approaches to infection control.
Day-200 nonrelapse mortality (NRM), recurrence or progression of cancer, relapse-related mortality, and overall mortality, adjusted for comorbidity scores, source of donor cells, donor type, patient age, disease severity, conditioning regimen, patient and donor sex, and cytomegalovirus serostatus.
During the 2003-to-2007 and 2013-to-2017 periods, 1148 and 1131 patients, respectively, received their first transplant. Over the decade, decreases were seen in the adjusted hazards of day-200 NRM (hazard ratio HR, 0.66 95% CI, 0.48 to 0.89), relapse of cancer (HR, 0.76 CI, 0.61 to 0.94), relapse-related mortality (HR, 0.69 CI, 0.54 to 0.87), and overall mortality (HR, 0.66 CI, 0.56 to 0.78). The degree of reduction in overall mortality was similar for patients who received myeloablative versus reduced-intensity conditioning, as well as for patients whose allograft came from a matched sibling versus an unrelated donor. Reductions were also seen in the frequency of jaundice, renal insufficiency, mechanical ventilation, high-level cytomegalovirus viremia, gram-negative bacteremia, invasive mold infection, acute and chronic graft-versus-host disease, and prednisone exposure.
Cohort studies cannot determine causality, and current disease severity criteria were not available for patients in the 2003-to-2007 cohort.
Improvement in survival and reduction in complications were substantial after allogeneic transplant. Relapse of cancer remains the largest obstacle to better survival outcomes.
National Institutes of Health.
Parametric response mapping (PRM) is a novel computed tomography (CT) technology that has shown potential for assessment of bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell ...transplantation (HCT). The primary aim of this study was to evaluate whether variations in image acquisition under real‐world conditions affect the PRM measurements of clinically diagnosed BOS. CT scans were obtained retrospectively from 72 HCT recipients with BOS and graft‐versus‐host disease from Fred Hutchinson Cancer Research Center, Karolinska Institute, and the University of Michigan. Whole lung volumetric scans were performed at inspiration and expiration using site‐specific acquisition and reconstruction protocols. PRM and pulmonary function measurements were assessed. Patients with moderately severe BOS at diagnosis (median forced expiratory volume at 1 second FEV1 53.5% predicted) had similar characteristics between sites. Variations in site‐specific CT acquisition protocols had a negligible effect on the PRM‐derived small airways disease (SAD), that is, BOS measurements. PRM‐derived SAD was found to correlate with FEV1% predicted and FEV1/ forced vital capacity (R = −0.236, P = .046; and R = −0.689, P < .0001, respectively), which suggests that elevated levels in the PRM measurements are primarily affected by BOS airflow obstruction and not CT scan acquisition parameters. Based on these results, PRM may be applied broadly for post‐HCT diagnosis and monitoring of BOS.
Parametric response mapping, a potential indicator of bronchiolitis obliterans syndrome following hematopoietic cell transplant, was examined in a multicenter setting and is shown to be applicable using a variety of high resolution CT scan techniques.
Abstract
Background
Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a ...randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections.
Methods
Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28.
Results
From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval CI −.64 to −.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22–1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 13.3% vs 9/14 64.3%, respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo.
Conclusions
Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia.
Clinical Trials Registration
NCT02254408; EUDRA-CT#2014-002474-36.
Presatovir treatment was safe but did not improve viral or clinical outcomes in hematopoietic-cell transplant recipients with respiratory syncytial virus upper respiratory tract infections. Exploratory analyses suggest clinical benefit in hematopoietic-cell transplant patients with lymphopenia at presentation.
Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID‐19 patients. A higher frequency of pulmonary embolism (PE) than expected in ...COVID‐19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID‐19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID‐19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID‐19 may be related to PE and not necessarily always due to the parenchymal disease.
Highlights
Acute severe COVID‐19 infection can trigger pulmonary embolism. The exact incidence of pulmonary embolism in COVID‐19 patients is still unknown and is likely to be underestimated by the nonspecific presenting symptoms. For COVID‐19 patients, the hypoxemia or severe dyspnea symptoms may be related to PE and not necessarily always due to the parenchymal disease. The patients with persistent dyspnea or hypoxemia later in the course of the disease should prompt an investigation for PE.
Pretransplant pulmonary function tests provide baseline data by which to reference subsequent respiratory impairment, as well as important prognostic information, for the hematopoietic cell ...transplant (HCT) recipient. Abnormalities in forced expiratory volume in 1 second and diffusing capacity of carbon monoxide are associated with early respiratory failure and increased all-cause mortality after allogeneic HCT. These parameters have been incorporated into risk assessment calculators that may aid in clinical decision making. This article discusses the clinical implications of pulmonary function parameters and other risk factors for pulmonary complications in the context of evolving allogeneic HCT practice.
Purpose To compare the risks of serious health outcomes among hematopoietic cell transplantation (HCT) survivors versus a matched population of patients with cancer who did not undergo HCT, where the ...primary difference may be exposure to HCT. Methods Two-year HCT survivors treated at a comprehensive cancer center from 1992 through 2009 who were Washington State residents (n = 1,792; 52% allogeneic and 90% hematologic malignancies) were frequency matched by demographic characteristics and underlying cancer diagnosis (as applicable) to non-HCT 2-year cancer survivors, using the state cancer registry (n = 5,455) and the general population (n = 16,340) using driver's license files. Late outcomes for all three cohorts were ascertained from the state hospital discharge and death registries; subsequent cancers were ascertained from the state cancer registry. Results After median follow-up of 7.1 years, HCT survivors experienced significantly greater rates of hospitalization compared with matched non-HCT cancer survivors (280 v 173 episodes per 1,000 person-years, P < .001) and greater all-cause mortality (hazard ratio HR, 1.1; 95% CI, 1.01 to 1.3). HCT survivors had more hospitalizations or death with infections (10-year cumulative incidence, 31% v 22%; HR, 1.4; 95% CI, 1.3 to 1.6) and respiratory complications (cumulative incidence, 27% v 20%; HR, 1.4; 95% CI, 1.2 to 1.5). Risks of digestive, skin, and musculoskeletal complications also were greater among HCT versus non-HCT cancer survivors. The two groups had similar risks of circulatory complications and second cancers. Both HCT and non-HCT cancer survivors had significantly greater 10-year cumulative incidences of all major organ-system outcomes versus the general population. Conclusion History of HCT was associated with late morbidity and mortality among cancer survivors. In particular, clinicians who care for HCT survivors should be aware of their high rates of late respiratory and infectious complications.
The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is poorly characterized. Understanding the trajectory of ...lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies.
To describe the longitudinal trajectory of lung function parameters, including FEV
, in patients with BOS after hematopoietic cell transplant.
Subjects with BOS defined by National Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV
for each patient was calculated on the basis of available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis to 6 months, and 6-18 months after diagnosis. The effect of treatment on FEV
trajectory was analyzed by univariate and multivariate linear regression. The Kaplan-Meier method was used to estimate survival.
The FEV
percent predicted value at diagnosis was 46% (interquartile range, 35-57%) for trial participants and 53% (interquartile range, 41-64%) for the retrospective cohort. There was a concomitant mild reduction in FVC, as well as a marked reduction in forced expiratory flow, midexpiratory phase, at diagnosis. While there was individual heterogeneity, the overall FEV
trajectory was characterized by a marked decline within 6 months prior to BOS diagnosis, followed by stability of FEV
early after diagnosis and a slow rate of decline beyond 6 months. The effect of the trial medications on FEV
trajectory after BOS diagnosis was a mean rate of change of 0.92% predicted per month (95% confidence interval, -0.53 to 2.37) compared with the retrospective cohort, but this was not statistically significant. Two-year overall survival rates were 76% and 72% for the study participants and the retrospective cohort patients, respectively. Earlier time to diagnosis after hematopoietic cell transplant and severity of FVC at diagnosis were significantly associated with reduced survival.
The FEV
trajectory in patients with BOS after hematopoietic cell transplant in a contemporary era of management follows a predominant pattern of rapid FEV
decline in the 6 months prior to diagnosis, followed by FEV
stabilization after diagnosis.
Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective ...multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection. We establish HHV-6B DNA viral load thresholds in BALF that are highly predictive of HHV-6B mRNA detection and associated with increased risk for overall mortality and death from respiratory failure. Participants with HHV-6B DNA in BALF exhibit distinct host gene expression signatures, notable for enriched interferon signaling pathways in participants clinically diagnosed with idiopathic pneumonia. These data implicate HHV-6B as a pulmonary pathogen after allogeneic HCT.
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