Primary Mediastinal Large B-Cell Lymphoma: Long Term Results with an Alternating Chemotherapy Regimen Based on High-Dose Methotrexate.

Primary mediastinal large B-cell lymphomas (MLCL) differ from other diffuse large cell lymphomas: they convey a unique gene expression profile reminding of Hodgkin’s disease, are characterized by an occlusive infiltration pattern (e.g. with vena cava superior syndrome due to the concomitant sclerosis) and treatment with CHOP-based chemotherapy regimen has been disappointing. A dose intensification improves long-term results, but no standard therapy has been established so far. We investigated the use of a high-dose methotrexate based alternating chemotherapy regimen (B-ALL protocol of the GM-ALL) first as a single-center, later as a multicenter trial in 43 patients; depending on the extend of the disease mediastinal radiotherapy and/or high-dose chemotherapy with stem cell rescue were applied additionally.

15 patients have been included in our pilot single-center study (median age 31.5 years). 11/15 (73%) showed infiltration of either esophagus, pleura, lung or V.cava superior syndrome, 6/15 (40%) had pericardial effusion. In this cohort 14/15 (93%) achieved a remission (10/15 CR, 4/15 PR), which is long lasting up to 15 years as observed for the first CR patients.

28 patients have been included into the recent multicenter trial. Here the rate of evaluable remissions after 6 cycles of chemotherapy was identical with 95% (18/19) complete or partial remissions. However, 2 patients died after the first cycle of chemotherapy following septic complications. In 136 chemotherapy cycles the rates of a grade 3 or 4 toxicity were 21% (mucositis), 41% (neutropenia), 30% (thrombocytopenia) and 10% (neutropenic fever).

A methotrexate based alternating chemotherapy regimen leads to excellent remission rates in patients with primary mediastinal large B-cell lymphoma. With regard to the patients included in our single-center trial with a long follow-up these remissions are reliable and long-lasting. Nevertheless, early death following treatment initiation does occur and requires close monitoring and treatment in specialized institutions.