Risk of Latent Tuberculosis Reactivation After Hematopoietic cell Transplantation.

There were no cases of tuberculosis in a cohort of 2531 patients who underwent hematopoietic cell transplantation from 2010 to 2015 after 7323 person-years of follow up (95% confidence interval [CI], 0.0-0.05 cases/100 person-years), including 29 (1.15%) patients with untreated latent tuberculosis after 89 person-years of follow-up (95% CI, 0.0-4.06 cases/100 person-years).

A Comparison of the Myeloablative Conditioning Regimen Fludarabine/Busulfan with Cyclophosphamide/Total Body Irradiation, for Allogeneic Stem Cell Transplantation in the Modern Era: A Cohort Analysis.

With improvement in transplantation practices in the modern era, nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has improved, while disease relapse rates have remained unchanged. Survival outcomes are therefore driven by NRM in the modern era. Myeloablative conditioning (MAC) regimens are used to maximize disease control and facilitate engraftment; however, their use is often limited by toxicity. The commonly used MAC regimens incorporate either chemotherapy plus total body irradiation (TBI) or combination chemotherapy. Furthermore, reduced-toxicity myeloablative (RTM) regimens, such as fludarabine/busulfan (FluBu), have emerged as alternatives to traditional MAC and their impact on outcomes in the current era have not been fully investigated. In this study, we compare outcomes following HSCT, using the chemotherapy only RTM MAC regimens FluBu with the chemoradiotherapy regimen cyclophosphamide/TBI (CyTBI), for patients with hematologic malignancies who underwent MAC HSCT at the Dana-Farber Cancer Institute. We hypothesized that the chemotherapy-only regimen would fare better, primarily due to improved NRM. A retrospective cohort analysis was performed on 387 patients with myeloid or lymphoid hematologic malignancies who underwent HLA-matched related (8/8), matched unrelated (8/8), or single-antigen mismatched unrelated (7/8) HSCT following myeloablative conditioning. Patients received FluBu (n = 158) or CyTBI (n = 229). The primary outcome was overall survival (OS) and all other outcomes were regarded as secondary. A subset analysis was performed for patients <55 years of age and for acute myelogenous leukemia/myelodysplastic syndrome patients of age <55 years. For the whole cohort, 3-year OS was similar for FluBu compared with CyTBI in unadjusted analysis. However, in multivariable analysis, FluBu resulted in superior OS compared with CyTBI (3-year adjusted estimate: 65% versus 55%, respectively; HR for death, .62; 95% CI, .40 to .97; P = .036). While relapse rates were similar between the 2 regimens, NRM and acute graft-versus-host disease (GVHD) (grade II to IV) were significantly worse with CyTBI compared with FluBu. Rates of chronic GVHD were similar between 2 regimens. These results were consistent in a subset of patients <55 years of age and in acute myelogenous leukemia/myelodysplastic syndrome patients below 55 years of age. The RTM chemotherapy-only regimen FluBu appears to be as effective and more tolerable than the chemoradiotherapy regimen CyTBI, leading to better OS driven by better NRM. The improvement in NRM was attributable chiefly to lower rates of grade II to IV acute GVHD. Relapse rates were not increased with FluBu. In the absence of randomized data, FluBu appears to be the optimal regimen for myeloablative HSCT in patients of all age groups.

Improved Treatment-Related Mortality and Overall Survival of Patients with Grade IV Acute GVHD in the Modern Years.

The impact of advances in supportive care and hematopoietic stem cell transplantation (HSCT) practices on the outcomes of patients who develop grade III or IV acute graft-versus-host disease (GVHD) is unknown. We performed a retrospective analysis of 427 patients with overall grade III or IV acute GVHD treated at 2 partner institutions between 1997 and 2012. We compared treatment-related mortality (TRM) and overall survival (OS) in 2 cohorts based on the year of transplantation, 1997 to 2006 (n = 222) and 2007 to 2012 (n = 205), using multivariate analysis, adjusting for significant patient-, disease-, and transplantation-related factors. Recipient age, reduced-intensity conditioning, unrelated donor, and peripheral blood stem cell grafts in the patients with grade III or IV acute GVHD increased over time. In the unadjusted analysis, 12-month OS increased over time (30% in 1997 to 2006 versus 42% in 2007 to 2012; P = .003) reflecting a decrease in TRM (58% in 1997 to 2006 versus 38% in 2007 to 2012; P = .0002), and an increase in PFS (29% in 1997 to 2006 versus 43% in 2007 to 2012; P = .002). On multivariate analysis, the period of transplantation remained a significant predictor for OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54 to 0.94; P = .02), progression-free survival (PFS) (HR, 0.70; 95% CI, 0.52 to 0.94; P = .02), and TRM (HR, 0.57; 95% CI, 0.39 to 0.82; P = .002). In subgroup analysis, these differences were observed mainly in patients with grade IV acute GVHD. The outcomes of patients who develop overall grade III or IV acute GVHD after allogeneic HSCT has improved over time, with lower TRM and improved OS. This improvement in outcomes was seen primarily in patients with grade IV acute GVHD.

The utility of routine chest radiography in the initial evaluation of adult patients with febrile neutropenia patients undergoing HSCT.

BACKGROUND: The routine use of chest radiographs (CXRs) in the initial evaluation of asymptomatic patients with febrile neutropenia undergoing hematopoietic stem cell transplant (HSCT) is controversial. OBJECTIVE: The goal of this study was to document the incidence of pneumonia demonstrated on CXR during an initial febrile neutropenic episode in adult patients undergoing HSCT. MATERIALS AND METHODS: Clinical records of 1083 adult patients undergoing autologous (n=766), allogeneic (n=269), or umbilical cord blood HSCT (n=48) between October 1, 2009, and December 31, 2012, were retrospectively reviewed. CXRs obtained at the initial febrile neutropenic episode were evaluated for radiologic features of pneumonia. The presence of clinical symptoms, length of stay (LOS), and readmission rates were assessed. RESULTS: A total of 817 (75%) febrile neutropenic episodes were noted. Of the patients with neutropenic fevers, 455 (55%) had CXRs. Of the 76 patients with respiratory symptoms at the time of CXR, 24 (31.6%) had findings suggestive of pneumonia. None of the 379 CXRs performed in the absence of symptoms revealed an infectious process (P=.0001). Moreover, the mean LOS was 23.8 days for patients receiving a CXR compared with 22.2 days (P=.04) in patients without a CXR. Additionally, in patients who had CXRs, 15.7% were readmitted within 30 days compared with 7.4% in those without CXRs (P=.0004). CONCLUSIONS: Indiscriminate routine CXR at the time of first neutropenic fever in asymptomatic adults undergoing HSCT is unlikely to reveal an infectious process or change clinical practice, and may be associated with increased LOS and readmission rates.

Improvements in Sepsis-associated Mortality in Hospitalized Patients with Cancer versus Those without Cancer. A 12-Year Analysis Using Clinical Data.

Rationale: There have been advances in both cancer and sepsis treatment over the past several decades, yet little is known about trends in sepsis-associated mortality in patients with versus without cancer.Objectives: To assess trends in sepsis-associated mortality in hospitalized patients with and without cancer using objective clinical criteria to identify sepsis and detailed clinical data to adjust for severity of illness.Methods: This was a retrospective cohort study at a tertiary referral hospital and cancer center. Adult in-patients with clinical indicators of sepsis (U.S. Centers for Disease Control and Prevention Adult Sepsis Event criteria) were identified between 2003 and 2014. Patients with cancer were identified using diagnosis codes from their hospitalization or the preceding 90 days. Sepsis-associated in-hospital mortality rates were assessed in 3-year intervals. Multivariable logistic regression models were used to adjust for case mix and severity of illness and to test for subgroup interactions in trends.Results: The cohort included 20,975 patients with sepsis, of whom 7,489 (35.7%) had cancer (61.7% solid and 38.3% hematologic). Sepsis-associated mortality rates in patients with cancer decreased from 31.3% in 2003-2005 to 26.0% in 2012-2014 (absolute decrease, 5.2% [95% confidence interval (CI), 2.3-8.2%]). This mortality reduction persisted after risk adjustment (adjusted odds ratio, 0.53 [95% CI, 0.45-0.63] in 2012-2014 relative to 2003-2005). In contrast, sepsis-associated mortality rates increased in patients without cancer from 20.9% in 2003-2005 to 23.9% in 2012-2014 (absolute increase, 2.1% [95% CI, 0.1-4.1%]), but were stable after risk-adjustment (adjusted odds ratio, 0.90 [95% CI, 0.79-1.03]) (P < 0.001 for comparison of trends between patients with vs. without cancer on both crude and adjusted analysis). Among patients with cancer, declines in risk-adjusted sepsis-associated mortality were observed in both solid and hematologic cancer subgroups, with both community-onset and hospital-onset sepsis, in patients receiving active cancer treatments, and in patients requiring mechanical ventilation at sepsis onset.Conclusions: Sepsis-associated mortality rates declined significantly over a 12-year period in patients with cancer, but not in patients without cancer. Potential explanations include advances in the management of cancer and/or better sepsis treatments specifically in patients with cancer. Further research is needed to elucidate the reasons for our findings and to assess their generalizability to other hospitals.

Integrative omics to detect bacteremia in patients with febrile neutropenia.

BACKGROUND: Cancer chemotherapy-associated febrile neutropenia (FN) is a common condition that is deadly when bacteremia is present. Detection of bacteremia depends on culture, which takes days, and no accurate predictive tools applicable to the initial evaluation are available. We utilized metabolomics and transcriptomics to develop multivariable predictors of bacteremia among FN patients. METHODS: We classified emergency department patients with FN and no apparent infection at presentation as bacteremic (cases) or not (controls), according to blood culture results. We assessed relative metabolite abundance in plasma, and relative expression of 2,560 immunology and cancer-related genes in whole blood. We used logistic regression to identify multivariable predictors of bacteremia, and report test characteristics of the derived predictors. RESULTS: For metabolomics, 14 bacteremic cases and 25 non-bacteremic controls were available for analysis; for transcriptomics we had 7 and 22 respectively. A 5-predictor metabolomic model had an area under the receiver operating characteristic curve of 0.991 (95%CI: 0.972,1.000), 100% sensitivity, and 96% specificity for identifying bacteremia. Pregnenolone steroids were more abundant in cases and carnitine metabolites were more abundant in controls. A 3-predictor gene expression model had corresponding results of 0.961 (95%CI: 0.896,1.000), 100%, and 86%. Genes involved in innate immunity were differentially expressed. CONCLUSIONS: Classifiers derived from metabolomic and gene expression data hold promise as objective and accurate predictors of bacteremia among FN patients without apparent infection at presentation, and can provide insights into the underlying biology. Our findings should be considered illustrative, but may lay the groundwork for future biomarker development.

Impact of physician assistants on the outcomes of patients with acute myelogenous leukemia receiving chemotherapy in an academic medical center.

PURPOSE: Inpatient academic medical center care historically has been delivered by faculty physicians in conjunction with physicians in training (house officers [HOs]). Alternative staffing models have emerged secondary to American Counsel for Graduate Medical Education work-hour restrictions. The purpose of this study was to assess the quality of acute myelogenous leukemia (AML) care provided by a physician assistant (PA) service compared with a traditional model. PATIENTS AND METHODS: Data were retrospectively collected on patients admitted with AML for reinduction chemotherapy from 2008 to 2012. Primary outcome measures were inpatient mortality and length of stay (LOS). Secondary measures included readmissions, intensive care unit (ICU) transfers, consults requested, and radiologic studies ordered. RESULTS: Ninety-five patients with AML were reviewed. Forty-seven patients (49.5%) were admitted to the HO service, and 48 patients (50.5%) were admitted to the PA service. Demographic data were similar between services. LOS was significantly different between the services, with a mean of 36.8 days with the HO model compared with 30.9 days with the PA service (P=.03). The 14-day readmission rate also differed significantly; it was 10.6% (five of 47 patients) and zero for the HO and PA models, respectively (P=.03). The mean number of consults with the HO model was 2.11 (range, zero to five) versus 1.47 (range, zero to four) with the PA service (P=.03). Mortality and ICU transfers were not significantly different. CONCLUSION: The data demonstrate equivalent mortality and ICU transfers, with a decrease in LOS, readmission rates, and consults for patients cared for in the PA service. This suggests that the PA service is associated with increased operational efficiency and decreased health service use without compromising health care outcomes.