haematologica vol. 87(12):december 2002 Background and Objectives. This multinational retrospective study compares the outcomes of patients with primary medi- astinal large B-cell lymphoma (PMLBCL) with sclerosis after first-generation (dose-intensive regimens), third-generation (alternating regimens) and high-dose chemotherapy strate- gies, frequently with adjuvant radiation therapy. Design and Methods. Between August 1981 and December 1999, a total of 426 previously untreated patients with con- firmed diagnosis were enrolled in 20 institutions to receive combination chemotherapy with either first generation (CHOP or CHOP-like) regimens, third generation (MACOP- B, VACOP-B, ProMACE CytaBOM) regimens or high-dose chemotherapy (HDS/ ABMT). Results. With chemotherapy, complete response (CR) rates were 49% (50/ 105), 51% (142/ 277) and 53% (23/ 44) with first generation, third generation and high-dose chemotherapy strategies, respectively; partial response (PR) rates were 32%, 36% and 35%, respectively. All patients who achieved CR and 124/ 142 (84%) with PR had radia- tion therapy on the mediastinum. The final CR rates became 61% for CHOP/ CHOP-like regimens, 79% for MACOP-B and other regimens, and 75% for HDS/ ABMT. After median fol- low-ups from attaining CR of 48.5 months for CHOP/ CHOP- like regimens, 51.7 months for MACOP-B type regimens and 32.4 months for HDS/ ABMT, relapses occurred in 15/ 64 (23%), 27/ 218 (12%) and 0/ 33 (0%) patients, respec- tively. Projected 10-year progression-free survival rates were 35%, 67% and 78%, respectively ( p=0.0000). Projected 10-year overall survival rates were 44%, 71% and 77%, respectively ( p=0.0000), after median follow-ups from diag- nosis of 52.3 months, 54.9 months and 35.8 months, respectively. Interpretation and Conclusions. In patients with PMLBCL with sclerosis, MACOP-B plus radiation therapy may be a better strategy than other treatments; these retrospective data need to be confirmed by prospective studies. The I n the new Revised European American Lym- phoma (R.E.A.L.) classifi cation, 1 primary medi- astinal large B-cell lymphoma (PMLBCL) with sclerosis is listed as a specific clinical and patho- logic entity. Histologically, this lymphoma is char- acterized by a diffuse proliferation of large B-cells with clear cytoplasm and by the presence of a vari- able degree of sclerosis, which causes the typical compartmentalization pattern. 2,3,4 Clinically, there is a predominant female to male ratio, and patients are commonly in the 25- to 40-year age group. PMLBCL with sclerosis presents as a rapidly grow- ing invasive tumor with contiguous spread within mediastinal masses. Chest pain, cough, and dyspnea are common. B symptoms are frequently present, and 30% to 40% of patients have superior vena cava obstruction. Pleural and pericardial invasion with effusion are common. The lesion is frequently bulky and often involves the thymus. Although PMLBCL with sclerosis was originally believed to have a particularly adverse prognosis, the outcome of patients who receive chemotherapy or combined modality treatment is now considered equivalent to that of patients with other large cell lymphomas of equivalent stage. Treatment with first-generation Induction chemotherapy stategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients PIER LUIGI ZINZANI , M AURIZIO M ARTELLI , M ARILENA BERTINI , ALESSANDRO M. GIANNI , LILIANA DEVIZZI , M ASSIM O FEDERICO, GERASSIM OS PANGALIS, J ORG M ICHELS, EM ANUELE ZUCCA, M ARIA CANTONETTI , SERGIO CORTELAZZO, ANDREW WOTHERSPOON, ANDRÉS J.M. FERRERI , FRANCESCO ZAJA, FRANCESCO LAURIA, AM ALIA DE RENZO, M ARINA A. LIBERATI , BRUNANGELO FALINI , M ONICA BALZAROTTI , ANTONELLO CALDERONI , ALFONSO ZACCARIA, PATRIZIA GENTILINI , PIER PAOLO FATTORI , ENZO PAVONE, M ARIA K. ANGELOPOULOU, LAPO ALINARI , M AURA BRUGIATELLI , NICOLA DI RENZO, FRANCESCA BONIFAZI , STEFANO A. PILERI , FRANCO CAVALLI FOR THE I NTERNATIONAL EXTRANODAL LYM PHOM A STUDY GROUP (IELSG) Correspondence: Pier Luigi Zinzani, M.D., Istituto di Ematologia e Oncologia Medica “Seràgnoli” Policlinico S.Orsola, via Massarenti 9, 40138 Bologna, Italy. Phone: international +39.051.390413. Fax: international +39.051.398973. E-mail: plzinzo@med.unibo.it Malignant Lymphomas research paper haematologica 2002; 87:1258-1264 http://www.haematologica.org/2002_12/1258.htm Institute of Hematology and Medical Oncology “Seràgnoli”, University of Bologna, Italy; Department of Cell Biotechnology, “La Sapienza” University, Rome, Italy; Division of Hematology, Molinette Hospital, Turin, Italy; National Institute of Tumor, Milan, Italy; G.I.S.L., Italy; Department of Internal Medicine, National and Kapodistrian University of Athens, Greece; The Wessex Medical Oncology Unit, Southampton University, United Kingdom; Division of Oncology, S.Giovanni Hospital, Bellinzona, Switzerland; Chair of Hematology, University “Tor Vergata”, Rome, Italy; Division of Hematology, Bergamo Hospital, Italy; The Royal Marsden Hospital, London, United Kingdom; S.Raffaele Hospital Scientific Institute, Milan, Italy; Chair of Hematology, University of Udine, Italy; Chair of Hematology, Siena Universi- ty, Italy; Chair of Hematology, University of Naples, Italy; Insti- tute of Internal Medicine, University of Perugia, Italy; Chair of Hematology, University of Perugia, Italy; Division of Oncology, Humanitas Institute, Rozzano, Italy; Institute of Medical Oncology, University of Berne, Switzerland; Division of Hematology, Ravenna Hospital, Italy; Division of Oncology, Forlì Hospital, Italy; Division of Oncology, Rimini Hospital, Italy; Chair of Hematology, University of Bari, Italy encouraging survival results after high dose chemotherapy require confirmation in selected high-risk patients. © 2002, Ferrata Storti Foundation Key words: PMLBCL, chemotherapy, radiotherapy, response rate, combined modality treatment.