Aggressive Primary Chemotherapy Plus Autologous Stem Cell Transplantation Improves Outcome for Peripheral T Cell Lymphomas Compared with CHOP-Like Regimens.

In the past two decades we have observed improvement in the outcome of patients diagnosed with some subtypes of lymphoma. However, the prognosis of patient with peripheral T-cell lymphoma (PTCL) still remains unsatisfactory. We prospectively evaluated aggressive chemotherapy and autologous stem cell transplantation (ASCT): IVE/MTX-ASCT in patients with de-novo PTCL.

Patients and methods: The regimen was piloted from 1997 for new patients eligible for intensive treatment: first for pts with enteropathy associated T-cell lymphoma (EATL) and subsequently for other types of PTCL. This therapy delivers one cycle of CHOP, followed by 3 courses of IVE (ifosfamide, etoposide, epirubicin), alternating with intermediate dose methotrexate (MTX). Stem cells are harvested after IVE and complete remissions (CR) were consolidated with myeloablative ASCT. The patients were evaluated with an intent to treat analysis for feasibility, response, progression free survival (PFS) and overall survival (OS).

57 patients were treated with the aggessive regimen, 26 pts had EATL and 31 other types of PTCL: 17 peripheral T-cell lymphoma NOS, 6 anaplastic T-cell lymphoma ALK positive, 4 extranodal NK/T cell lymphoma nasal type, 3 anaplastic T-cell lymphoma ALK negative and 1 hepatosplenic gamma/delta T-cell lymphoma. The median age at diagnosis was 51 years (range 23 – 69), 36/57 (63%) pts were male and 27/55 (49%) presented with ECOG >1. Early stage disease was diagnosed in 22/57 (39%) pts and advanced disease in 35/57 (61%). Bone marrow was involved in 6/53 (11%) pts and LDH was elevated in 23/46 (50%). Among pts with primary nodal disease 14/26 (54%) had at least one extranodal site involved and 6/26 (23%) bulky disease.

At present, 55 pts are available for response evaluation. Eight pts discontinued treatment prematurely; 4 due to toxicity (one severe sepsis and death, one severe encephalopathy, one bone marrow failure and one bleeding from the gastrointestinal tract), and four pts due to disease progression. Of the remaining 47 pts 33 went on to receive ASCT. ASCT was omitted due to: refractory disease in 5 pts, poor general condition in 4 pts, insufficient stem cell mobilisation in 4 pts and one pt declined further treatment. The most common severe toxicities were pancytopenia, infection, nausea/vomiting and obstruction/perforation. Complete remission was confirmed in 39/55 (71%) pts, partial remission in 3/55 (5%) pts and 13/55 (24%) pts failed the treatment. The remission rates were: CR-17/26 (65%) pts and PR-1/26 (4%) for EATL and 22/29 (76%) and 2/29 (7%), respectively for other PTCL. During the study time 17/57 (30%) pts died, 15 due to lymphoma. For all pts 3-years PFS was 59% and OS 67%. For pts with EATL the 3-years PFS and OS were 52% and 60% and for other types 65% and 72%, respectively. These results were unchanged after the exclusion of anaplastic T-cell lymphoma ALK positive: (61% and 72%, respectively).

For patients with PTCL, we propose that intensive chemotherapy and ASCT significantly improves outcome compared to CHOP-like regimens, and has acceptable toxicities. In conclusion, where feasible patients with PTCL should be considered for aggressive treatments, like IVE/MTX – ASCT as primary therapy.

No relevant conflicts of interest to declare.