Risk and Response Adapted Treatment of Primary Mediastinal B-Cell Lymphoma (PMBCL): Single Institutional Experience
Authors: Falorio Simona , Angrilli Francesco , Fioritoni Francesca , Santarone Stella , Fioritoni Giuseppe 
Published: April 2020

Abstract
Background: PMBCL accounts for nearly 2% of all non Hodgkin lymphoma. The most effective treatment of this disease is unknown. In retrospective studies third generation chemotherapy regimens, namely MACOP-B or VACOP-B, plus radiotherapy achieved better results in comparison with conventional CHOP. Moreover, the value of the addition of rituximab (R) to CHOP or MACOP-B in PMBCL is not well-known today. The purpose of this study is to evaluate the results of our experience in the treatment of PMBCL.
Methods: Between 1/2000 and 1/2008, 25 untreated patients (pts) with PMBCL have been admitted in our institution. Disease evaluation was performed with whole-body computed tomography at diagnosis, after 3–4 courses or after 2 months of chemotherapy and at the conclusion of treatment. At early restaging, pts who obtained at least a partial remission (PR) completed planned treatment, while unresponsive pts started high dose sequential chemotherapy (HDSC) (2 courses of APO, 2 courses of DHAP, cyclophosphamide 7gr/m2, methotrexate 8gr/m2, etoposide 2gr/m2) followed by autologous stem cells transplantation (ASCT). In a first time, the planned treatment generally consisted of third generation chemotherapy (PROMACE-CYTABOM in 5 pts and MACOP-B in 1 pt) plus involved field radiotherapy (IFRT) (36 Gy). Another patient with high risk disease (stage IVB, aaIPI 3) received front-line HDSC plus ASCT. One patient aged 16 years was treated according NHL97-AIEOP pediatric protocol (drugs total dose mg/m2, course A: iphosphamide 4000, methotrexate 5000, cytarabin 300, etoposide 200, vincristine 1,5. Course B: cyclophosphamide 1000, methotrexate 5000, daunomycin 50, vincristine 1,5. Course C: cytarabin 12000, etoposide 500, vindesine 3) plus IFRT (36 Gy). Subsequently, for the remaining 17 pts, planned treatment consisted of R-CHOP chemo-immunotherapy (CHOP21 in 4 cases and CHOP14 in 13 cases) plus IFRT (36 Gy). Retrospectively, we evaluated the response rate, overall survival (OS) and disease free survival (DFS).
Results: 5 pts were male and 20 female (M/F ratio: 0,25); median age was 32 years. Stage I–II was present in 20 pts and stage III–IV in 5; aa-IPI was 0–1 in 20 pts and 2–3 in the remaining 5. Fifteen pts (60%) had B symptoms at the time of diagnosis. After early restaging, 21 pts (84%) showed at least a PR. The other 4 pts, who were treated with third generation chemotherapy (1/6, 17%) or R-CHOP (3/17, 18%) and who were early unresponsive, received treatment intensification with HDSC followed by ASCT in 2 cases. At present, 1 patient died of sepsis during MACOP-B, 2 pts are still under treatment and 22 pts completed treatment. We obtained a complete remission (CR) in 19 pts (86%) and a PR in 2 pts (9%). One of the last 2 pts achieved CR after HDSC plus ASCT. Overall, 5 pts received treatment intensification (4 after early restaging and 1 after treatment completion). With a median follow-up of 44 months, OS was 87% and DFS of the 20 CR pts was 100%. Two pts (1 with PR, 1 with unresponsive disease) died of progressive lymphoma. No difference in response and outcome was seen between third generation chemotherapy and R-CHOP.
Conclusions: various chemo-radiotherapic combinations have been used successfully in the treatment of PMBCL. Waiting for prospective studies aimed to define a gold standard treatment, we think that our response-adapted treatment modality is an effective approach for inducing durable response in the majority of pts with PMBCL.