Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group.

This prospective multi-institutional phase II study was designed to assess the efficacy and safety of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphomas. Eighty-one patients diagnosed with diffuse large B-cell lymphoma (DLBCL, n = 68), primary mediastinal DLBCL (n = 6) and follicular lymphoma Grade 3b (n = 7), with an age-adjusted International Prognostic Index >1, were eligible for analysis. Median age was 60 years (range: 21-77). Sixty-five patients (80·2%) achieved complete response. After a median follow-up time of 64 months, 10-year event-free survival and overall survival (OS) were 47·8% and 63·6%, respectively. None of the studied clinical and biological characteristics were associated with poorer outcome. Interestingly, patients with BCL6 rearrangement achieved a 10-year OS of 100%, while patients with BCL2 rearrangement exhibited a poorer outcome compared to activated B-cell tumours and germinal centre B-cell without BCL2 rearranged tumours. Results achieved with DA-EPOCH-R showed a good long-term outcome and a tolerable toxicity profile in high-risk large B cell lymphoma patients. Outcome was not affected by tumour cell proliferation or by cell of origin, highlighting the requirement of new biological markers for patient subclassification of high-risk DLBCL patients.

Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults.

BACKGROUND & AIMS: Despite consensus recommendations, eosinophilic esophagitis (EoE) is commonly diagnosed upon esophageal eosinophilic infiltration (EEI; based on ≥ 15 eosinophils per high power field; eo/HPF). We evaluated the prevalence of EEI before and after proton pump inhibitor (PPI) therapy and assessed the accuracy of EEI and pH monitoring analyses. METHODS: Biopsies were taken from the upper-middle esophagus of 712 adults with upper gastrointestinal symptoms who were referred for endoscopy due to upper gastrointestinal symptoms. Patients with EEI were treated with rabeprazole (20 mg, twice daily) for 2 months. EoE was defined by persistent symptoms and >15 eo/HPF following PPI therapy. RESULTS: Thirty-five patients (4.9%) had EEI, of whom 55% had a history of allergies, and 70% had food impaction or dysphagia as their primary complaint. Twenty-six EEI patients (75%) achieved clinicopathological remission with PPI therapy; of these, 17 had GERD-like profile (EEI <35 eo/HPF and objective evidence of reflux, based on endoscopy or pH monitoring), and 9 had EoE-like profile (EEI 35-165 eo/HPF, typical EoE symptoms and endoscopic findings). The PPI response was 50% in the EoE-like profile patients. The PPI-response was 50% in EoE-like profile patients. Likewise, PPI-responsive EEI occurred with normal (33%) and pathologic (80%) pH monitoring. Higher histologic cut-off values improved specificity and positive predictive for EoE (35%-35% for >20 eo/HPF; 46%-39% for >24 eo/HPF; 65%-50% for 35 eo/HPF). CONCLUSIONS: In adults with EEI, 75% of unselected patients and 50% with an EoE phenotype respond to PPI therapy; pH monitoring is poorly predictive of response. Patients with PPI-responsive EEI >35 eo/HPF are phenotypically undistinguishable from EoE patients. EoE might be overestimated without clinical and pathologic follow-up of patient response to PPI.

Overlap of reflux and eosinophilic esophagitis in two patients requiring different therapies: a review of the literature.

Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have overlapping clinical, manometric, endoscopic and histopathologic features. The diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per high power field (eo/HPF) in esophageal biopsies. We report the cases of two young males suffering from dysphagia and recurrent food impaction with reflux esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of which became asymptomatic on proton pump inhibitor (PPI) therapy. The first patient also achieved a histologic response, while EE remained in the other patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring. Topical steroid therapy combined with PPI led to complete remission in this latter patient. GERD and EE may be undistinguishable, even by histology, so diagnosis of EE should only be established after a careful correlation of clinical, endoscopic and pathologic data obtained under vigorous acid suppression. These diagnostic difficulties are maximal when both diseases overlap. Limited data are available about this topic, and the interaction between EE and GERD is a matter of debate. In this setting, upper-mid esophagus step biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to evaluate the role of each disease. A PPI trial is mandatory in patients with a histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE should be suggested. However, a clinical response to PPI may not rule out quiescent EE, as shown in this report.