Hyperchidam Verona897 Regimen Is Effective in Treatment of Advanced Peripheral T Cell Lymphoma (PTCL): The GITIL Experience in 33 Cases

Background. Peripheral T cell Lymphoma (PTCL) represent a major therapeutic challenge. In the previous Verona experience (Todeschini G et al. Cancer 2005;104:555–560), the novel intensive regimen HyperCHiDAM Verona897 (high-dose IV MTX 2 g/sqm 400 sqm bolus, 1600 sqm CI day 1 with IV leucovorin rescue; hyperfractionated IV CTX 300 mg/sqm Q12h, dd 2–4; high-dose IV AraC 2g/sqm Q12h, dd 2-4; plus G-CSF) achieved salutary results in refractory/relapsed aggressive lymphomas, in particular in PTCL. Supportive measures included hydratation 3000 ml/sqm/day, antimicrobial prophylaxis comprising oral ciprofloxacin, itraconazole, trimethoprim/sulfamethoxazole. CMV antigenemia (pp65) was monitored 2 times a week. Patients. Following these results, 7 centers belonging to the Italian co-operative group GITIL (Gruppo Italiano Terapie Innovative Linfomi) treated with 2 cycles of HyperCHiDAM Verona897, 33 patients affected by PTCL (17 upfront, 16 refractory/relapsed) followed in the majority of cases by stem cell transplant. Patients: M/F 21/12, median age 49 (19–63) years; histology: PTCL-NOS 15, ALCL ALK-negative 9, EALTC 4, AIL 3, T-NK nasal 1, Angiocentric 1; stage IV 19/33 (57.5%), bone-marrow positive 10/33 (30.3%), extranodal involvement 24/33 (72.7%), high LDH 18/33 (54.5%). Seven patients needing urgent treatment were treated before HyperCHiDAM with 1 cycle of Campath-CHOP (4 patients) or CHOP + L-ASE (3 patients). Results. Upfront patients: after 2 cycles of HyperCHiDAM, CR were 82.3% (14/17), early toxic deaths 0 (1 late toxic death occurred after SCT, due to CMV pneumonia), relapses 3/14. With a median follow-up of 21 months (3–90+), 11/17 (64.7%) patients are disease-free, 10 in first CR, 1 after rescue with stem cell transplant. Three of the CCR patients received HyperCHiDAM alone. Refractory/relapsed patients: CR were 5/16 (31.2%), CCR 4/16 (25%), with a median follow-up of 24 months (5–64+). The progression-free survival was significantly superior in upfront patients (p=0.036). Overall, toxic deaths were 3/33 (9%), 1/17 (5.8%) in upfront and 2/16 (12.5%) in refractory/relapsed patients. One patient had major cerebellar toxicity. Conclusions. The intensive regimen HyperCHiDAM Verona897 is effective in inducing CR in aggressive PTCL, in particular as upfront therapy. The intensiveness of this treatment requires a careful supportive therapy. Following these results, HyperCHiDAM has been included in a national trial for treatment of PTCL, after 2 cycles of Campath-CHOP and before stem cell transplant (allogeneic or autologous depending on the availability of an HLA-matched sibling). The co-operative study is recruiting.