Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease

Rosai-Dorfman disease is a rare subtype of non-Langerhans cell histiocytosis. With the last major report published in 1990, there is a paucity of contemporary data on this disease. Our objective was to report the clinicopathological features, treatments and outcomes of patients seen at a tertiary referral center. Sixty-four patients with histopathological diagnosis of Rosai-Dorfman disease were identified from 1994 to 2017 (median age 50 years; range, 2-79). The median duration from symptom onset to diagnosis was seven months (range, 0-128), which was also reflected in the number of biopsies required to establish the diagnosis (median 2; range, 1-6). The most common presentation was subcutaneous masses (40%). Of the 64 patients, 8% had classical (nodal only) and 92% had extra-nodal disease (67% extra-nodal only). The most common organs involved were skin and subcutaneous tissue (52%), followed by lymph nodes (33%). Three patients had an overlap with Erdheim-Chester disease, which had not been described before. Two of these were found to have MAP2K1 mutations. Commonly utilized first line treatments were surgical excision (38%) and systemic corticosteroids (27%). Corticosteroids led to a response in 56% of the cases. Of those treated initially, 15 (30%) patients developed recurrent disease. The most commonly used systemic agent was cladribine (n=6), with 67% overall response rate. Our study demonstrates that Rosai-Dorfman disease has diverse clinical manifestations and outcomes. While this disease has been historically considered a benign entity, a subset of patients endures an aggressive course necessitating the use of systemic therapies

Procalcitonin as a biomarker for predicting bacterial infection in chimeric antigen receptor T‐cell therapy recipients

Abstract Background It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T‐cell (CAR‐T) recipients present with a constellation of signs and symptoms that may represent both complications. Objective The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR‐T recipients. Study design This single‐center, retrospective, medical record review evaluated patients prescribed CAR‐T therapy until death or 30 days after infusion. Logistic regression modeling determined the association between elevated serum PCT concentrations within 48 h of fever onset and microbiologically confirmed infection. Secondary outcomes included clinically suspected infection, CAR‐T toxicity rates, and broad‐spectrum antibiotic usage. Predictive performance of PCT was assessed by area under the receiver operating characteristic curve (AUC). Results The 98 included patients were a median age of 63 (IQR: 55–69) years old, 47 (48%) were male, and 87 (89%) were Caucasian. Baseline demographics and clinical characteristics were similar between patients with and without a bacterial infection. Serum PCT >0.4 ng/mL within 48 h of fever was significantly associated with a microbiologically confirmed bacterial infection (OR: 2.75 [95% CI: 1.02–7.39], p = 0.045). Median PCT values in patients with and without confirmed infections were 0.40 ng/mL (IQR: 0.26, 0.74) and 0.26 ng/mL (IQR: 0.13, 0.47), respectively. The AUC for PCT to predict bacterial infection was 0.62 (95% CI 0.48–0.76). All patients experienced CRS of some grade, with no difference in CRS severity based on elevated PCT. Broad‐spectrum antibiotics were used for a median of 45% and 23% of days in those with and without confirmed infection, respectively (p = 0.075). Conclusion Elevated serum PCT concentrations above 0.4 ng/mL at time of first fever after CAR‐T infusion was significantly associated with confirmed bacterial infection. Furthermore, rigorous, prospective studies should validate our findings and evaluate serial PCT measurements to optimize antimicrobial use after CAR‐T therapy

International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma

Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as time from date of diagnosis to progression after primary treatment, retreatment, or death. Subsequent OS was measured after achieving EFS24 or from the time of progression if it occurred within 24 months. OS rates were compared with the age-, sex-, and country-matched general population. Results Seven hundred seventy-five patients were included in the study (the median age at diagnosis was 64 years; 63% were men). Results were similar in the initial and replication cohorts, and a combined analysis was undertaken. Sixty-four percent of patients progressed within the first 24 months and had a median OS of only 4.9 months (5-year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5-year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in 23% of patients. Superior outcomes after achieving EFS24 were observed in younger patients (≤ 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or early relapse have extremely poor survival. However, more than one third of patients with PTCL remain in remission 2 years after diagnosis with encouraging subsequent OS, especially in younger patients. These marked differences in outcome suggest that EFS24 has utility for patient counseling, study design, and risk stratification in PTCL