Frontline High-Dose Therapy (HDT) for Adults with Disseminated Aggressive Lymphoma (NHL): Analysis of 327 Patients Included in 3 Prospective Trials (GOELAMS 071, 072, 074) over 12 Years.

We have demonstrated in a randomised prospective trial (GOELAMS 072) that front line HDT including an autologous stem cell transplantation improved significantly the EFS and OS as compared to standard CHOP regimen in adults with aggressive NHL and a high-intermediate age-adjusted-IPI (NEJM 2004). In order to further precise the benefit and risks as well as the prognostic factors with that type of treatment we decided to analyse the patients who entered the high-dose arm of successive prospective GOELAMS’ trials designed for patients 15 to 60 y.o. with non previously treated aggressive NHL (excluding mantle cell, Burkitt, Lymphoblastic and transformation of known low grade) Ann.Arbor. stage II with abdominal bulk (> 7cm), III and IV, HIV neg and having given an informed consent (GOELAMS 071 BJH 2000; GOELAMS 072; GOELAMS 074 Blood 2004- ASH). Over a 12 years period 327 pts entered the high-dose arm of these trials. The median age was 44 yo, 60% male, 91% stage III/IV, 65% LDH>N, 33% PS≥2, 30% aa-IPI interm-low, 50% aa-IPI interm-high, 20% aa-IPI high. Histology was Diffuse large cell in 237, anaplastic in 29 and peripheral T cell in 16. Overall 75% of the pts received the planned treatment with autologous transplant. The median FU for surviving patients is 57 m (2 to 148m). The KM 5y and 10y survival is 63% and 55% respectively. Overall 114 pts died a median of 13 m after inclusion (1–130m). The main cause of death was lymphoma relapse or progression (86 pts-75% of the deaths); 12 pts died from TRM; 4 from second cancer (3 solid, 1 MDS). In UV analysis prognostic factors for OS were: PS=4, LDH>4xN, Peripheral T cell LNH. The median, KM 5y and 10y EFS are 77m, 51% and 49% respectively. In UV analysis prognostic factors for EFS were LDN>4xN and Peripheral T cell LNH.

These results confirm that intensive short term treatment is able to produce long term survival for a high number of patients with intermediate or poor prognosis without long term toxicity at least in term of second cancer. For T cells LNH and very high LDH levels other treatments are needed.