The Role of High Dose Therapy and Stem Cell Rescue in the Management of T-Cell Malignant Lymphomas (TCL): A BSBMT and ABMTRR Study.

Abstract

Malignant lymphoma of a T-cell phenotype (TCL) account for only 15% of lymphomas in Europe/North America and associated with a poorer prognosis compared with B-cell phenotype lymphomas. Whilst cumulative experience has shown that high dose chemotherapy and autologous stem cell rescue (ASCT) is an effective salvage therapy in B-cell disease the role of ASCT and especially full intensity Allogeneic stem cell transplantation (HSCT) in T-cell disease, is limited. This study represents a collaborative retrospective case analysis of patients undergoing ASCT/HSCT for T-cell lymphoma. The aim of the study was to determine the impact of ASCT/HSCT on disease responsiveness, treatment-related toxicities and to examine influencing factors in relation to outcomes. All recipients of ASCT and HSCT performed in 1990 through 2002 for PTCL and reported to the British Society of Bone Marrow Transplantation (BSBMT) and the Australian Bone Marrow Transplant Recipient Registry (ABMTRR) were eligible for the study and data was examined retrospectively using a structured data retrieval proforma. Eighty-three patients received high dose therapy for TCL (ASCT n=65, HSCT n=18) with a median age of 28 years (12–52 yrs) in the HSCT group and 45 years (17–70 yrs) in the ASCT group, p<0.0001. Histological categorisation was heterogeneous with 30/65 patients (42%) in the ASCT group and 9/18 patients (32%) in the HSCT group being TCL-NOS, p<0.0001. The median number of therapies prior to ASCT and HSCT were similar (2, range 1–7) including 2 patients in the HSCT group who had received a prior ASCT. Disease status at transplant was: CR1 (ASCT 48%, HSCT 33%), CR2 (ASCT 6%, HSCT 6%), PR (ASCT 23%, HSCT 44%) and progressive disease (ASCT 22%, HSCT 17%). 54% of patients in the ASCT group received BEAM conditioning and 67% of the HSCT group received TBI-based regimen supported by matched-related (13/18), matched-unrelated (4/18) haplo-identical (1/18) grafts. With a median follow-up from ASCT of 18.3 months (range 1–100 months) 34 patients were alive; 21 died of progressive disease, 4 died from sepsis and 5 died from pneumonia. With a median follow-up from HSCT of 30 months (range 1–89 months), 5 patients were alive; 5 died of progressive disease, 3 died of acute GvHD (6/18 experienced grade II-IV acute GvHD), 4 died from sepsis and 1died from a secondary malignancy. The 5 yr OS is 45% in the ASCT group and 29% in the HSCT group (p=0.06) and the 5 yr PFS is 42% in the ASCT group and 22% in the HSCT group (p=NS). The 5 yr relapse rates were 32% and 28% (p=NS) in the ASCT and HSCT groups, respectively with a higher non-relapse mortality (NRM) in the HSCT group compared with the ASCT group (50% vs 23%, p=0.024). In a multi-variate analysis, the only factor to significantly impact both OS and PFS was chemosensitive disease (p=0.015 & p>0.01, respectively). These results suggest that ASCT has a significant role in the management of TCL, though full intensity HSCT is limited by both high NRM and limited evidence of graft-versus-lymphoma effect. Further exploration of reduced intensity HSCT may help to establish a role for HSCT in the management of TCL.