Adult lymphoblastic lymphoma: a retrospective analysis of 92 patients under 61 years included in the LNH87/93 trials S Le Gouill 1 , S Lepretre 2 , J Brie `re 3 , P Morel 4 , R Bouabdallah 5 , E Raffoux 3 , C Sebban 6 , E Lepage 7 and P Brice 3 1 Hotel Dieu, Nantes, France; 2 Centre Henri Becquerel, Rouen, France; 3 Hopital Saint-Louis, Paris, France; 4 Hopital de Lens, France ; 5 Institut Paoli Calmette, Marseille, France; 6 Centre Le ´on Be ´rard, Lyon, France; and 7 Hopital Henri Nondor Giteil Since 1987, the GELA has initiated multicenter prospective trials for aggressive non-Hodgkin’s lymphomas (NHL). Lym- phoblastic lymphomas (LBL) were included in those studies until 1997, and 92 LBL patients under 61 years were identified after histological review. The protocols prescribed high-dose anthracycline regimens, four cycles given every 15 days as induction and lasted for p6 months. A total of 23 patients underwent high-dose therapy consolidation followed by auto- logous stem-cell transplantation and 69 received standard chemotherapy regimens. Clinical characteristics showed a male predominance (66%) with a median age of 31 years, bone marrow (BM) involvement (22%), mediastinal involvement (66%) and elevated LDH (62%). At the end of treatment, it was seen that 71% of the patients achieved complete remission; four (4%) patients died during induction; 43 patients relapsed at a median time of 10 months. With a median follow-up of 34 months, the 5- year overall survival (OS) and event-free survival (EFS) rates were 32 and 22%, respectively. The only favorable factor significantly associated with survival was young age. These results are poorer than those obtained in other aggressive lymphomas treated with the same regimens and suggest that adult LBL patients should be treated with acute lymphoblastic leukemia protocols. Leukemia (2003) 17, 2220–2224. doi:10.1038/sj.leu.2403095 Keywords: adult lymphoblastic lymphoma; chemotherapy Introduction Lymphoblastic lymphomas (LBL) are classified as high-grade non- Hodgkin’s lymphomas (NHL) in the Working Formulation and represent o2% of NHL. 1 This rare disease occurs mainly in young males and is clinically characterized by frequent media- stinal, pleural, pericardial or meningeal involvement. A large majority (80%) of LBL has a T-cell phenotype. The clinical distinction between LBL and acute lymphoblastic leukemia (ALL) is arbitrary, based on nodal involvement, the degree of bone- marrow (BM) infiltration and the presence of blast cells in the peripheral blood (PB). A patient with a nodal presentation, minimal or no BM involvement and no blast cells in PB is currently diagnosed as having LBL. However, ALL and LBL can be considered as two different manifestations of the same disease. 2–4 Since LBL are a rare entity, treatment remains uncertain. Different chemotherapy regimens used to treat aggressive lymphoma or ALL have been administrated as induction therapy. 5,6 Consolidation with chemotherapy or autologous stem-cell transplantation (ASCT) has also been given. 7,8 Allogeneic stem-cell transplantation is mostly restricted to patients in first complete remission (CR) with a factor of poor risk. 8,9 The small number of patients with LBL and the difficulty in diagnosing it explain why there are actually very few prospective trial comparing these approaches. From 1987 to 1997, LBL could be included in GELA trials for aggressive lymphomas provided they had no BM or central nervous system (CNS) involvement. We decided to analyze the outcomes of patients under 61 years at diagnosis with LBL confirmed after histological re-examination of the slides from two prospective adult lymphoma trials (LNH87 and LNH93) conducted by the GELA in an attempt to identify prognostic factors for survival. Materials and methods Patient selection From January 1987 to September 1997, 7656 newly diagnosed patients, 16–69 years old, with intermediate or high-grade (HG) NHL, according to the International Working Formulation, were included in the LNH87 or LNH93 trials. These patients were negative for the human immunodeficiency virus, and had no concomitant or previous cancer, uncontrolled diabetes mellitus, congestive heart failure, recent myocardial infarction or con- duction abnormalities or kidney dysfunction. At diagnosis, the patients were staged according to the Ann Arbor system. 10 Disease dissemination was evaluated before treatment by physical examination, BM biopsy, cerebrospinal fluid examination and computed tomography scan of the chest and abdomen, and other investigations according to the clinical symptoms. Performance status (PS) was assessed according to the Eastern Cooperative Oncology Group (ECOG) scale (0–4). 11 In the LNH87 study, patients with HG-NHL were stratified into four prognosis groups according to the factors defined by clinical status (age, PS, number of extra nodal sites, tumor burden X10 cm for the largest diameter and BM or CNS involvement). In the LNH93 study, patients with HG-NHL were also stratified into different groups according to the age-adjusted international prognosis index (IPI) for patients p61 years old: lactate dehydrogenase (LDH), stage and PS. 12 LBL patients could be included in these studies provided they had no CNS or BM involvement at inclusion. After giving their informed consent, patients were randomly assigned through a central procedure to the different arms of these trials. After histological review of the slides of all patients included in the two trials, 120 (1.6%) patients (67 in LNH87 and 53 in LNH93) were finally diagnosed as having LBL. Many of these patients were diagnosed as LBL only after this histological re- evaluation of their biopsy, thus explaining why some patients had BM or CNS involvement at diagnosis. Among 99 patients who were p61 years old at initial diagnosis, data were incomplete for seven. Thus, 92 patients were retained for this retrospective analysis. Histopathology Three independent hematopathologist members of the GELA performed the histological review and their observations were Received 5 March 2003; accepted 19 June 2003 Correspondence: Dr P Brice, HDJ He ´matologie, Ho ˆ pital Saint-Louis AP-HP, 1, avenue Claude Vellefaux, 75475 Paris, Cedex 10, France; Fax: þ 33 01 42 49 92 92 Leukemia (2003) 17, 2220–2224 & 2003 Nature Publishing Group All rights reserved 0887-6924/03 $25.00 www.nature.com/leu