Efficacy of High-Dose Sequential Chemotherapy and Autograft for Transformed Non Hodgkin’s B Cell Lymphoma: Results of a Retrospective Analysis from GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

Background - Follicular lymphoma (FL) transforms in a more aggressive lymphoma in 25–60% of patients representing the outgrowth of a more malignant subclone. Transformation is usually associated to a rapidly progressive clinical course, refractoriness to treatment, and short survival. To define the impact of high dose sequential (HDS) therapy and peripheral blood stem cell (PBSC) autograft on outcome of transformed FL (TFL), we analyzed a consecutive series of 66 pts with a confirmed diagnosis of TFL registered at the GITIL centers from March 1988 to September 2004 and treated with the HDS regimen.

Methods - Biopsy-proven histological transformation (HT) in diffuse large B cell lymphoma (DLBCL) was observed at diagnosis (n=24; 36%) or at relapse after a treatment for FL (n= 42; 64%). Main patient characteristics were as follows: male/female 36/30; median age 51 yrs (range 33–66), stage I-II/III-IV 8/58, IPI score 0–1/≥2 28/38. HDS regimen included: i. 3 APO or 3 DHAP courses (for patients relapsed after anthracycline-containing regimens); ii. sequential administration of hd-CTX (7g/mq), hd-Ara-C, (2g/mq q12h for 6 days) hd-Etoposide (2.4 g/mq), with PBSC harvests following hd-CY and hd-Ara-C; iii. myeloablative regimen with hd-Mitoxantrone/L-Pam (n=28) or BEAM (n=28 pts who could not receive additional anthracycline), or TBI-PAM (n=3); iv. PBSC autograft; v. consolidation radiotherapy on bulky disease. From January 1999, hd-CTX and hd-Ara-C has been supplemented with Rituximab (RHDS; n=34) with in-vivo purging intent.

Results - Overall 59 patients achieved a complete remission (CR; 89%), 1 patient responded partially and underwent allogeniec bone marrow transplantation, 6 patients died for progressive disease while on therapy (PD; 9%). With a median follow-up of 67 months (range 23–170), 42 patients are alive (63.6%), 24 patients relapsed and died for progressive disease (n= 23) or toxicity (n= 1). Five-year event free survival (EFS) and overall survival (OS) are 53.0% and 63.6%, respectively. No significant differences in OS and EFS were observed between patients with HT at diagnosis or at relapse, with IPI O-1 vs IPI >2. Of note, pts treated with R-HDS showed an improved clinical outcome (OS: 76% vs. 50%; EFS: 67.6 vs. 37.5 respectively), with a large difference that did not reach statistical significance because of the limited number of patients.

Conclusion - Our data strongly suggest that HDS regimen, in particular when supplemented with rituximab (R-HDS), is a very effective regimen in transformed B cell lymphoma.