Long-Term Follow-Up of High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Peripheral T-Cell Lymphomas at Diagnosis.

Background: Limited experience is available on the feasibility and long-term efficacy of high-dose (HD) chemotherapy followed by autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL) at diagnosis.

Patients and methods: Between January 1993 and December 2003, 54 patients (median age 44 years, range 20-61; 66% male) with PTCL with high-risk features were candidate to HD chemotherapy and ASCT as a first-line treatment. Histologic PTCL subtypes included: PTCL not otherwise specified (n=25), ALCL alk-positive (n=17), angioimmunoblastic (n=9), others subtypes (n=4). 44 patients (81%) presented with stage III or IV, 58% had elevated s-LDH and 73% presented with two or more adverse risk factors according to the International Prognostic Index (IPI). Treatment program consisted of: 1) induction and intensification phase with two APO and two DHAP courses than either the sequential administration at 15-20 days intervals of HD-cyclophosphamide, HD-cytarabine and HD-etoposide (n=26) or 8 weeks of MACOP-B followed by HD-cytarabine and mitoxantrone (MAD) (n=29); 2) consolidation phase with HD-mitoxantrone and HD-melphalan (n=12) or BEAM (n=27) followed by ASCT; 3) radiotherapy on bulky sites.

Results: Thirty-nine patients (71%) attained a clinical response (n=32 CR; n=7 PR) and were autografted while 16 patients (29%) did not for the following reasons: progressive disease (n=10), toxicity (n=2), toxic death concomitant with refractory disease (n=2), refusal (n=2). At a median follow-up of 66 months (range, 10-127 months), 27 patients (49%) are alive (25 in CR) and 28 died (51%): 21 for disease progression, 5 for treatment-related-toxicity and 2 for other reasons (n=1 other disease, n=1 car accident). The estimated 2-year TRM was 7 %. Using an intention-to-treat-analysis, the estimated 5 year overall survival (OS) and progression-free survival (PFS) projections were 52% (95% CI, 38% to 66%) and 50% (95% CI, 36% to 64%) respectively. Patients autografted with ALCL alk-pos subtype had a better prognosis compared to other subtypes with 5 year OS of 84% versus 52% (P<0.03) and 5 year PFS of 84% versus 36% (P<0.01), respectively. No statistical difference in PFS or OS was observed between patients treated with either sequential HD therapy or MACOP-B/MAD. Univariate analysis revealed no significant differences in OS and PFS for patients with IPI score <2 versus ≥ 2.

Conclusions: Our study indicates that up-front HD and ASCT: 1) induces a high rate of long term remission in patients with ALCLalk-pos subtype; 2) is of limited benefit in patients with non-ALCLalk-pos subtype whose expected long-term progression free survival was lower than 40%. In this subgroup other treatment options including consolidation with allogeneic transplantation from HLA identical donor, should be evaluated.