Excellent Results In the Treatment of Primary Mediastinal Lymphomas

Abstract 4915

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) with unique clinical and radiological appearance and distinct histopathologic and genetic features. PMBCL accounts for approximately 3% of primary lymphoid tumors. Because of the relative rarity of this disease there are not enough prospective randomised trials with sufficient number of patients and therefore there is not a standard treatment either. Before the rituximab era contradictory results were published with standard cyclophosphamide, doxorubicin, oncovine, prednisone (CHOP) treatment and radiotherapy. The most favourable results were obtained with the combination of third-generation regimens (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin/MACOP-B/, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin/VACOP-B/) and radiotherapy. Immuno-chemotherapy has been an important step forward in the efficiency of the treatment of PMBCL patients. The addition of rituximab (R) to the standard CHOP-21 regimen has significantly improved the remission rate, the overall survival (OS), the event-free survival (EFS) and the disease-free survival rate. An American working group has obtained more than 90% OS and EFS rates with using dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) alone without radiotherapy (Dunleavy et al, Blood 2005). A German working group published excellent results with CHOP-14 treatment of DLBCL patients younger than 60 years and with R-CHOP-14 treatment of elderly patients (Pfreundschuh et al, Blood 2004 and Pfreundschuh et al, Blood 2005). We have treated 23 newly diagnosed PMBCL patients with R-CHOP-14 regimen between July 2005 and July 2009. The median age of the 17 women and 6 men was 32 years (range 21–53). 11 patients had stage I and another 11 patients had stage II disease. Among these patients 4 and 3 cases had extranodal manifestations (5 pleural, 3 pericardial and 2 lung infiltrations). Only 1 patient had stage IV disease (with lung involvement). Elevated lactate dehydrogenase (LDH) levels were found in 22 cases. Bulky mediastinal tumor (>10 cm) was observed in 18 patients but all 23 patients had a mass larger than 7 cm. All 23 patients were considered to have good prognosis (revised International Prognostic Index/R-IPI/: 1–2). The mean number of chemotherapy regimens was 7,1 (range 4–8). In 20 cases radiotherapy (average dose 36 Gy) was used post chemotherapy as consolidative treatment. As a result, 21 patients obtained complete remission confirmed with a PET/CT scan. In 1 case even the repeated PET/CT scan could not clear the effect of the therapy but she is supposedly in complete remission because of the relatively long event-free survival and the morphologic improvement of the CT image. One patient who only obtained partial remission after chemotherapy and stayed PET/CT scan positive, underwent autologous stem cell transplantation and then achieved complete remission confirmed with PET/CT scan. During the median 32 months follow-up (range 12–61) no relapse has occurred. One patient died of acute arterial haemorrhage due to an acute tuberculosis infection after 13 months follow-up time. The 3 years overall survival rate was 95,6% and the event-free survival rate was 91,3% respectively. The authors have found the well tolerable R-CHOP-14 regimen combined with radiotherapy very effective in PMBCL patients and recommend this treatment. This combination was found more effective than the third-generation or R-CHOP-21 regimens and similar to DA-EPOCH-R treatment. Decreasing or completely withholding the radiotherapy may be considered in cases of negative interim PET/CT scans.