Faculty Bibliography

Patients with classic Hodgkin lymphoma (cHL) who relapse after autologous hematopoietic cell transplantation (auto-HCT) historically have had poor outcomes. We hypothesized that, post-auto-HCT relapse, overall survival (PR-OS) has improved in recent years as a result of more widespread use of novel therapies and allogeneic HCT (allo-HCT). We conducted a retrospective study in 4 US academic centers, evaluating 215 patients who underwent auto-HCT from 2005 to 2016 and relapsed thereafter. Patients were divided into 2 cohorts based on timing of auto-HCT, 2005 through 2010 (cohort 1; n = 118) and 2011 to 2016 (cohort 2; n = 97), to compare differences in clinical outcomes. The median age and disease status at auto-HCT were similar in cohorts 1 and 2. The proportions of patients who received brentuximab vedotin (Bv; 55% vs 69%; P = .07), checkpoint inhibitors (CPIs; 3% vs 36%; P ≤ .001), and allogeneic-HCT (22% vs 35%, P = .03) were significantly different between cohorts 1 and 2, respectively. At the 5-year follow-up after auto relapse, 32% and 50% of patients were alive in cohorts 1 and 2, respectively (P = .01). In multivariate analysis for PR-OS, cohort 1 vs 2 (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.14-4.60; P = .01), age at auto-HCT (HR, 1.48; 95% CI, 1.18-1.87; P ≤ .001), and time to relapse from auto-HCT (HR, 0.59; 95% CI, 0.47-74; P ≤ .0001), retained independent prognostic significance for PR-OS. Our study supports the hypothesis that survival of cHL patients after auto-HCT failure has significantly improved in recent years, most likely because of incorporation of novel therapies and more widespread use of allo-HCT.

Outcomes for diffuse large B-cell lymphoma (DLBCL) patients relapsing after autologous hematopoietic cell transplantation (auto-HCT) have been historically poor. We studied outcomes of such patients using data from 4 transplantation centers. Eligibility criteria included adult patients (age ≥18 years) with DLBCL experiencing disease relapse after auto-HCT performed during 2006 to 2015. The time period was stratified into 2 eras (era 1, 2006-2010; era 2, 2011-2015). The primary end point was postrelapse overall survival (PR-OS). Secondary end points were factors prognostic of PR-OS. Of the 700 patients with DLBCL who underwent auto-HCT, 248 (35%) relapsed after auto-HCT. Median PR-OS of all relapsed DLBCL patients after auto-HCT (n = 228) was 9.8 months (95% confidence interval [CI], 7-15). Median PR-OS was significantly better for patients in complete (17.8 months; 95% CI, 7.9-41.6) vs partial remission at auto-HCT (7.1 months; 95% CI, 5.4-11; P = .01), those undergoing auto-HCT >1 year (12.8 months; 95% CI, 7.6-24.9) vs ≤1 year after DLBCL diagnosis (6.3 months; 95% CI, 4.5-9.2; P = .01), and those with late (56.4 months; 95% CI, 23.7-∞) vs early relapse (5.9 months; 95% CI, 4.5-8.8; P < .0001). On multivariate analysis, although late relapse (hazard ratio [HR], 0.21; 95% CI, 0.13-0.34; P < .0001) was associated with significantly lower mortality, the risk of mortality increased with age (HR, 1.25 per decade; 95% CI, 1.06-1.48; P = .009). This is the largest study to date to evaluate outcomes of DLBCL patients relapsing after auto-HCT. Our study provides benchmarking for future trials of chimeric antigen receptor T cells and other promising agents evaluating PR-OS after auto-HCT.

BACKGROUND:Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with a wide spectrum of presentation. While grade 1/2 FL is considered low grade and grade 3B FL is approached as an aggressive lymphoma, the management of grade 3A FL remains controversial. PATIENTS AND METHODS:We performed a retrospective, multicenter analysis of patients aged ≥ 18 years with advanced stage 3/4 grade 3A FL diagnosed between January 2006 and July 2016. Patients were stratified by frontline chemotherapy regimen: anthracycline based (ATC), bendamustine (BD), and cyclophosphamide, vincristine, and prednisone (CVP). A total of 103 patients were identified from 6 contributing centers: 65 patients received ATC chemotherapy, 30 BD, and 8 CVP. The primary outcome was time to progression (TTP). Secondary outcomes included progression-free survival, overall survival, complete response rates, large cell transformation, and impact of standardized maximum uptake value on positron emission tomography/computed tomography with outcomes. Patient characteristics were similar among the 3 treatment groups. RESULTS:For TTP at 24 months from initiation of treatment, 72% of ATC, 79% of BD, and 50% of CVP patients had not experienced disease progression (P = .01). Multivariate analysis demonstrated a TTP benefit for ATC compared to CVP (hazard ratio 3.22; 95% confidence interval, 1.26-8.25; P = .01) but no difference when compared to BD. Similar findings were seen with progression-free survival. While overall survival was similar among the 3 arms, there was a higher risk of large cell transformation following BD and CVP. Last, standardized maximum uptake value on positron emission tomography/computed tomography did not affect TTP when comparing BD- and ATC-treated patients. CONCLUSION:Although ATC was superior to CVP, clinical outcomes (TTP, progression-free survival, and overall survival) were similar compared to BD chemotherapy for patients with grade 3A FL.

Increasing evidence suggests that asymptomatic carriers are an important source of healthcare-associated Clostridium difficile infection. However, it is not known which test for the detection of C. difficile colonization is most sensitive in patients with haematological malignancies. We performed a prospective cohort study of 101 patients with haematological malignancies who had been admitted to the hospital for scheduled chemotherapy or haematopoietic cell transplantation. Each patient provided a formed stool sample. We compared the performance of five different commercially available assays, using toxigenic culture as the reference method. The prevalence of toxigenic C. difficile colonization as determined by toxigenic culture was 14/101 (14 %). The Cepheid Xpert PCR C. difficile/Epi was the most sensitive test for the detection of toxigenic C. difficile colonization, with 93 % sensitivity and 99 % negative predictive value. Our findings suggest that the Xpert PCR C. difficile/Epi could be used to rule out toxigenic C. difficile colonization in this population.

BACKGROUND:mutation have been reported, but this finding has not been confirmed in all studies. CASE PRESENTATION/METHODS:protein using immunohistochemistry. Before treatment of her histiocytic sarcoma could be initiated, she developed disseminated intravascular coagulation and acute hypoxemic respiratory failure secondary to non-cardiogenic pulmonary edema. She decided to pursue comfort care and died in our hospital 2 weeks following admission. CONCLUSIONS:mutation. Further research is needed to clarify the role of targeted therapies such as vemurafenib in the treatment of patients with this disorder.

Only a minority of patients with high risk lymphoma will be cured with autologous transplant, so maintenance with vorinostat, an oral agent with activity in relapsed lymphoma, was studied starting day + 60 for 21 consecutive days followed by a week off for up to 11 cycles. Twenty-three patients with lymphoma were treated. Ten patients completed the full 11-cycle treatment plan per protocol, four patients were removed due to progressive disease and seven withdrew or were removed from the study due to toxicities. Despite Prevnar vaccine administration every 2 months for three injections, the mean antibody concentration never reached protective levels (> 0.35 μg/mL). Fatigue and functional well-being measured by Brief Fatigue Inventory and Functional Assessment of Cancer Therapy-General improved significantly from cycle 1 to cycle 7, but depression scores from the Center for Epidemiologic Studies Depression scale did not change. Given the toxicities observed, this broad-spectrum deacetylase inhibitor at this schedule is not optimal for prolonged maintenance therapy.

UNLABELLED:Phenomenon: Medical students commonly participate in patient care in a variety of different settings. However, a systematic review of patients' attitudes toward medical student participation across specialties has not been performed. APPROACH/METHODS:The authors searched 7 databases (CINAHL, Cochrane Library, ERIC, MEDLINE, PsycINFO, Scopus, and Web of Science) between January 1, 1999, and August 5, 2014. Two authors independently screened the results and selected articles that were written in English, were published in a peer-reviewed journal, and used a structured or semistructured survey or interview to determine patients' attitudes toward medical student participation in their care. Study quality was assessed using the Medical Education Research Study Quality Instrument. FINDINGS/RESULTS:Fifty-nine studies were included. Average study quality was low. Sixty-one unique evaluation instruments were used, and 34 instruments (56%) lacked validity data. Patient satisfaction was not significantly affected by medical student participation. However, patients' acceptance of medical student participation varied widely between studies and depended on the type of participation. The most common reason for acceptance was a desire to contribute to the education of others, and the most common reason for refusal was concerns about privacy. Minorities were more likely to refuse medical student participation. Patients preferred to be informed before medical students participated in their care. Insights: Patient satisfaction is not significantly affected by medical student participation. However, patient satisfaction may be a poor surrogate marker of patients' acceptance of medical students. Future research should employ validated evaluation instruments to further explore patients' attitudes toward medical student participation.

Complement-mediated hemolytic uremic syndrome (otherwise known as atypical HUS) is a rare disorder of uncontrolled complement activation that may be associated with heart failure. We report the case of a 49-year-old female with no history of heart disease who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given her normal ADAMSTS13 activity, evidence of increased complement activation, and renal biopsy showing evidence of thrombotic microangiopathy, she was diagnosed with complement-mediated HUS. She subsequently developed acute hypoxemic respiratory failure secondary to pulmonary edema requiring intubation and mechanical ventilation. A transthoracic echocardiogram showed evidence of a Takotsubo cardiomyopathy with an estimated left ventricular ejection fraction of 20%, though ischemic cardiomyopathy could not be ruled out. Treatment was initiated with eculizumab. After several failed attempts at extubation, she eventually underwent tracheotomy. She also required hemodialysis to improve her uremia and hypervolemia. After seven weeks of hospitalization and five doses of eculizumab, her renal function and respiratory status improved, and she was discharged in stable condition on room air and independent of hemodialysis. Our case illustrates a rare association between acute systolic heart failure and complement-mediated HUS and highlights the potential of eculizumab in stabilizing even the most critically-ill patients with complement-mediated disease.