Is There a Role for Autologous Stem-Cell Transplantation (ASCT) in Peripheral T-Cell Lymphoma (PTCL)? Final Results of a Prospective Phase II Study from the GELCAB.

The outcome of patients (pts) with PTCL receiving conventional therapy is dismal. Because of this, there is an increasing interest to investigate intensive treatments in these patients. The aim of this study was to analyze the toxicity, response and outcome of a phase II trial that includes high-dose chemotherapy (CT) plus ASCT as first-line treatment for pts with PTCL. Forty-one pts (30M/11F; median age: 47 yrs.) diagnosed with PTCL (excluding cutaneous and anaplastic ALK+), in stages II-IV and <65 years were the subject of this analysis. Twelve pts (29%) presented with primary extranodal disease, 29 (71%) were in stage IV, and 14 (35%) had bone marrow involvement. Forty-six percent of the pts had high/intermediate or high-risk IPI, whereas 49% were in the groups 3 or 4 according to the Italian Index for PTCL. Pts received intensive CT (3 courses of high-dose CHOP [cyclophosphamide 2000 mg/m² day 1, adriamycin 90 mg/m² day 1, vincristine 2 mg day 1, prednisone 60 mg/m²/day, days 1 to 5, mesnum 150% of cyclophosphamide dose, G-CSF 300 mg/day days 7 to 14], alternating with 3 courses of standard ESHAP). Responders (CR or PR) were submitted to ASCT. Median follow-up of surviving pts was 3.2 years (range, 0.6–8.1). Twenty-eight pts (68%) received the planned 6 courses of CT. Response rate after CT was as follows: CR, 20 cases (49%); PR, 4 (10%); failure, 17 (41%), including one pt who died because of sepsis. Hematological toxicity of CT mainly consisted of neutropenia (median nadir after high-dose CHOP and ESHAP: 0.01 and 0.4x10⁹/L, respectively) and thrombocytopenia (23 and 29x10⁹/L, respectively). Severe infection requiring hospitalization was observed in 38 and 15% of courses of high-dose CHOP or ESHAP, respectively. Only 17 of the 24 candidates (41% of all pts) received ASCT due to the lack of stem-cell mobilization (3 cases), severe previous toxicity (2), early relapse of the lymphoma (1) and pt decision (1). No major toxicity was observed after ASCT. The overall response after the whole treatment was: CR, 21 cases (51%), PR, 3 (7%), failure, 17 (42%). Four-year failure-free survival (FFS) was 30% (95%CI: 14–46%), whereas 4-year EFS was 51% (95%CI: 29–73%). Twenty-two pts have died during follow-up, with a 4-yr OS of 39% (95%CI: 22–56%). Notably, no significant differences in the outcome were seen among the 24 pts candidates for ASCT according to whether or not they eventually underwent this procedure. Four of 17 transplanted and 4 of 7 nontransplanted pts eventually relapsed. In addition, 2 pts died in CR after ASCT due to the development of a Burkitt-like lymphoma and lung cancer at 18 and 5 months from the procedure. Thus, 4-year EFS was 59% (95%CI: 33–85%) and 29% (95%CI 0–73%) for transplanted and nontransplanted pts, respectively (p>0.1). Four-year OS was 57% (95%CI: 31–83%) and 71% (95%CI: 37–100%), respectively (p>0.1). In summary, in this series of patients with PTCL a relatively high CR rate was obtained with high-dose CHOP/ESHAP followed by ASCT. Toxicity was manageable. The contribution of ASCT to pts outcome is debatable because of the absence of significant differences in OS and EFS of patients in CR transplanted vs. those not transplanted. Novel strategies aimed at increasing the CR rate in these patients warrant investigation.