DA-EPOCH-R was administered as described previously
DA-EPOCH-R was administered as described previously.11,12 Disease sites were evaluated by CT scan after Sinomenine hydrochloride cycles 4 and 6 by using standard response criteria.13,14 The institutional review board approved the study, and all patients provided consent in accordance with the Declaration of Helsinki. Patients Sinomenine hydrochloride began on dose level 1 of DA-EPOCH-R (rituximab 375 mg/m2 day 1, doxorubicin 10 mg/m2 per day, etoposide 50 mg/m2 per day, and vincristine 0.4 mg/m2 per day [no cap]; continuous infusion days 1, 2, 3, and 4 (96-hour total); cyclophosphamide 750 mg/m2 30-minute infusion day 5; and prednisone 120 mg/m2 divided and administered in two separate doses on days 1, 2, 3, 4, and 5, as previously described.10 Patients received filgrastim 300 g on day 6 and continued until the absolute neutrophil count (ANC) reached 5000 cells per L past the nadir. cells, and tumor morphology were biomarkers of outcome in MGZL. Compared with PMBL, MGZL patients were more likely to be male, express CD15, have lower expression of CD20, and have a worse outcome. DA-EPOCH-R alone is effective in MGZL. The trial was registered at ClinicalTrials.gov (“type”:”clinical-trial”,”attrs”:”text”:”NCT00001337″,”term_id”:”NCT00001337″NCT00001337). Introduction Mediastinal B-cell lymphomas present in the mediastinum of young patients and are mostly represented by nodular sclerosis Hodgkin lymphoma (NSHL) and primary mediastinal B-cell lymphoma (PMBL).1-3 The most recent World Health Organization classification of lymphoid tissues recognized mediastinal gray-zone lymphoma (MGZL), a rare lymphoma with features intermediate between PMBL and NSHL, as a new pathological entity.3-5 Historically, these patients were often included in series of Hodgkin-like anaplastic large cell lymphoma, which was a heterogeneous group.6-8 The clinical characteristics and treatment of MGZL have yet to be defined because of its recent identification and rarity. NSHL and PMBL have both overlapping and distinct clinical features, raising the question of where MGZL lies within the pathological and clinical spectrum of mediastinal B-cell lymphomas. Therapeutically, the Hodgkin-like pathological features of MGZL suggest they should be treated like Hodgkin lymphoma (HL), whereas the strong expression of the CD20 B-cell protein by most MGZLs, a feature Sinomenine hydrochloride of PMBL but not NSHL, suggests they should be treated with rituximab-based regimens as with PMBL. As a Sinomenine hydrochloride group, mediastinal B-cell lymphomas are hypothesized to derive from a thymic B-cell.2,4,7,9 A significant proportion of PMBL and NSHL patients have amplification of the locus, which has also been reported in MGZL. 9 PMBL and NSHL also have overlapping gene expression profiles, indicating that they lie along a pathobiological continuum.2 MGZL has been described as the missing link between NSHL and PMBL.4 We undertook a study of untreated MGZL to describe its clinical outcome with the immunochemotherapy regimen of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R), an effective treatment of PMBL, and to describe its biological characteristics.10 Patients and methods Study design and treatment Twenty-four patients with untreated MGZL were prospectively enrolled between November 1999 and February 2013 on a study of DA-EPOCH-R at the National Cancer Itga7 Institute. Because of the recent recognition of MGZL as a distinct entity by our center in 2004, we amended our prospective study of DA-EPOCH-R in PMBL to add a separate cohort for MGZL. All but three patients were enrolled after this date. Objectives included event-free survival (EFS), overall survival (OS), and immunohistochemical analysis. Pathology was confirmed by S.P. or E.S.J. according to World Health Organization criteria.3 Eligibility included all disease stages and performance statuses, negative tests for HIV and pregnancy, and adequate organ function unless it was the result of involvement by lymphoma. Evaluation included standard blood tests, whole-body computed tomography (CT) scans, and bone marrow biopsy. DA-EPOCH-R was administered as previously described.11,12 Disease sites were evaluated by CT scan after cycles 4 and 6 by using standard response criteria.13,14 The institutional review board approved the study, and all patients provided consent in accordance with the Declaration of Helsinki. Patients began on dose level 1 of DA-EPOCH-R (rituximab 375 mg/m2 day 1, doxorubicin 10 mg/m2 per day, etoposide 50 mg/m2 per day, and vincristine 0.4 mg/m2 per day [no cap]; continuous infusion days 1, 2, 3, and 4 (96-hour total); cyclophosphamide 750 mg/m2 30-minute infusion day 5; and prednisone 120 mg/m2 divided and administered in two separate doses on days 1, 2, 3, 4, and 5, as previously described.10 Patients received filgrastim 300 g on day 6 and continued until the absolute neutrophil count (ANC) reached 5000 cells per L past the nadir. Dose adjustments were based on the neutrophil nadir, which was monitored with complete blood counts performed 2 times per week, and were made in 20% increments. Dose adjustments above the starting dose level applied to etoposide, doxorubicin, and cyclophosphamide, and adjustments below the starting dose level applied only to cyclophosphamide. Doses.