A prospective study of mediastinal gray-zone lymphoma

Abstract

Mediastinal B-cell lymphomas present in the mediastinum and are most frequent in young patients. Nodular sclerosis Hodgkin lymphoma (NSHL) and primary mediastinal B-cell lymphoma (PMBL) are the common types, whereas mediastinal gray-zone lymphoma (MGZL) is extremely rare and has pathological features intermediate between NSHL and PMBL. The indeterminate pathobiology of MGZL has led to uncertainty regarding therapeutic strategy, and its clinical characteristics and treatment have not been characterized. We conducted a prospective study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) and filgrastim in untreated MGZL. We analyzed biomarkers of outcome and compared their clinical and biological characteristics to PMBL. Twenty-four MGZL patients had a median age of 33 years (range, 14 to 59 years), and 46% had mediastinal masses ≥10 cm. At 59 months median follow-up, the event-free survival and overall survival were 62% and 74%, respectively. The serum absolute lymphocyte count, the presence of tumor-infiltrating dendritic cells, CD15 expression on the malignant 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 (NCT00001337).

Figure 1

MGZL IHC photomicrographs. (A) CD15⁺ biopsies showing low (1+) and high (4+) staining of malignant cells. (B) DC-SIGN–positive biopsies showing low (1+) and high (3+) staining of infiltrating dendritic/macrophage cells.

Figure 2

Kaplan-Meier plots of EFS and OS in MGZL. Twenty-four patients were prospectively treated with DA-EPOCH-R. Patients were observed for a median of 59 months (range, 7 to 142 months) and results are presented at 3 years. (A) Overall, EFS was 62% (95% CI, 42% to 79%), and (B) OS was 74% (95% CI, 51% to 89%). (C) EFS for patients with ALCs >880 cells per μL (the median) was 83% (95% CI, 55% to 95%), and for <880 cells per μL, it was 42% (95% CI, 19% to 68%), respectively (P = .038). (D) OS for patients with ALCs ≥880 cells per μL was 100% (95% CI, 74% to 100%), and for <880 cells per μL, it was 52% (95% CI, 24% to 78%), respectively (P = .028). (E) EFS for patients without or with tumor-infiltrating DC-SIGN–positive cells was 67% (95% CI, 35% to 88%) and 40% (95% CI, 17% to 69%), respectively (P = .18). (F) OS for patients without or with tumor-infiltrating DC-SIGN–positive cells was 100% (95% CI, 66% to 100%) and 52% (95% CI, 5% to 68%), respectively (P = .0025). (G) EFS for patients with CD15 scores of 0 to 2 vs 3 to 4 was 74% (95% CI, 50% to 90%) and 38% (95% CI, 14% to 69%), respectively (P = .16). (H) OS for patients with CD15 scores of 0 to 2 vs 3 to 4 was 93% (95% CI, 70% to 99%) and 38% (95% CI, 12% to 74%), respectively (P = .032).

Figure 3

Kaplan-Meier plots of EFS and OS of MGZL and PMBL. (A) EFS was 62% (95% CI, 42% to 79%) for MGZL (blue curve) compared with 93% (95% CI, 81% to 98%) for PMBL (red curve) at 5 years (P = .0005). (B) OS was 74% (95% CI, 51% to 89%) for MGZL (blue curve) compared with 97% (95% CI, 83% to 99%) for PMBL (red curve) at 5 years (P = .0012).