Patients with Mature T-Cell Lymphoma Show High Relapse Rates after High Dose Therapy and Autologous Stem Cell Transplantation
Authors: Nickelsen Maike , Canals Carmen , Schmitz Norbert , Kyriakou Charalampia , Engelhardt Monika , Relander Thomas , Linkesch Werner , Koza Vladimir , Meloni Giovanna , Lopez-Guillermo Armando , Indrac Karel , Caballero Dolores , Wandt Hannes , Theorin Niklas , Glass Bertram , Sureda Anna 
Published: October 2019

Abstract
Patients (pts) with mature (peripheral) T-cell lymphoma are known to have a poor prognosis when receiving standard conventional chemotherapy. This leads many physicians to regard high dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) as standard therapy for these pts. We here present a retrospective analysis on 424 pts with mature T-cell lymphoma who have received HDT and ASCT in EBMT centres between 2000 and 2005. Patients with primary cutaneous or immature (lymphoblastic) lymphoma were not included. Histological subtypes were anaplastic large cell lymphoma (ALCL, n=98, 23.1%; 19 anaplastic large cell kinase (ALK) positive, 42 ALK negative and for 37 pts the ALK status was unknown), peripheral T-cell lymphoma (PTCLu, n=176, 41.5%), angioimmunoblastic T-cell lymphoma (n=120, 28.3%) and aggressive T-cell lymphoma unspecified (n=30, 7.1%). Median age at ASCT was 51 years (17.2–73.5), median time from diagnosis to ASCT was 9 months (4–99), and median follow up for surviving pts was 36 months (0.4–99). 268 pts (63%) were male. 1/3 received HDT and ASCT after only one previous treatment line. 35% of the pts were treated in CR1, and 52% in chemosensitive disease worse than CR1. At the time point of ASCT only 12 pts (2.8%) had a poor performance status. 9% of the pts received total body irradiation as part of the conditioning regimen. At 3 years after ASCT non relapse mortality (NRM) was 7.4% and the relapse rate (RR) was 43.1%. In multivariate COX analysis for NRM refractory disease (p<0.001, relative risk 6.7) and poor performance status at ASCT (p=0.02, relative risk 3.2) were statistically significant adverse factors while the RR was significantly influenced by histology (PTCLu versus other subgroups, p=0.02, relative risk 1.4), and disease status at ASCT (refractory disease versus CR1 p=0.001, relative risk 3.3 and chemosensitive disease versus CR1 p=0.001, relative risk 1.9). At 3 years progression free survival (PFS) was 49.5% and overall survival (OS) 62.3%. In multivariate COX analysis adjusted for PFS refractory disease and chemosensitive disease worse than CR1 were significant adverse factors compared to CR1 (p<0.001 each, relative risk 3.2 and 1.7, respectively) as was refractory disease compared to chemosensitive disease (including CR1; p=0.004, relative risk 1.9). Other significant adverse factors were age at SCT 60 years (p=0.04, relative risk 1.4), poor performance status at ASCT (p=0.046, relative risk 2.1) and PTCLu versus other subgroups (p=0.02, relative risk 1.4). In summary there was a high RR for this group of pts who actually received ASCT. Especially refractory pts and pts in poor performance status did not benefit from the procedure. Further studies are necessary to better define the pts who will actually be cured by ASCT and to early identify the pts who will need other approaches and thus can be spared high dose chemotherapy which may negatively influence later salvage regimen.