Hematopoietic Stem Cell Transplantation in Hepatosplenic T-Cell Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party
Authors: Karsten Imke E. , Schmitz Norbert , Fekom Mathilde , de Leval Laurence , Finel Hervé , Khvedelidze Irma , Kim Won Seog , Wu Depei , Rovira Montserrat , WANG Fengrong , Huang Xiao-Jun , Dreger Peter , Maertens Johan , Corradini Paolo , Helbig Grzegorz , Bethge Wolfgang Andreas , Bacon Larry , Vydra Jan , Balaguer Rosello Aitana , Stelljes Matthias , Lenz Georg , Tanase Alina Daniela , Sureda Balari Anna , Bazarbachi Ali , Glass Bertram 
Published: December 2024

Introduction
Hepatosplenic T-cell lymphoma (HSTCL) is a very rare disease accounting for 1-2% of all peripheral T-cell lymphomas (PTCL). HSTCL shows a highly aggressive clinical course and often a very poor outcome. Guidelines mostly recommend aggressive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo HSCT) in responding and transplant-eligible patients (pts) although evidence is limited and data on transplant outcomes are scarce.
Methods
We conducted a retrospective analysis of EBMT registry data and data from registries of cooperating centers in China and South Korea. The following inclusion criteria were applied: pts with HSTCL confirmed by review of pathology reports (LdL) in 62 % of cases, first autologous or allogeneic stem cell transplantation (SCT) between 2003 and 2024. Outcome data were calculated from the day of transplantation until the respective event.
Results
After exclusion of pts with pathology reports not consistent with HSTCL, 121 pts were included in this analysis (100 pts from the EBMT registry and 21 pts from Asian registries). Of these, 94 pts underwent allo HSCT and 27 pts autologous HSCT.
Median age of allografted pts was 36 years (range 15-68; female 29 pts). 35 pts (38%) were allografted after 1 line of conventional therapy; 56 pts (62%) were transplanted after 2 or more lines of conventional therapy. Remission status at the time of allo HSCT was complete remission (CR) in 53 %, partial remission (PR) in 9 %, and chemorefractory/progressive disease (PD) in 38 % of pts.
With median follow-up of 4.5 years (95% CI: 3.1 - 6.2 years), the 1-year and 3-year progression-free survival (PFS) rates for 94 pts with allo HSCT were 59.6 % (95 % CI: 48.6 - 69 %) and 50.5 % (95 % CI: 39.4 - 60.5 %), respectively. One-year and 3- year overall survival (OS) rates were 67.7 % (95 % CI: 57.2 - 76.2 %) and 55 % (95 % CI: 43.9 - 63.4 %). The cumulative incidences of non-relapse mortality (NRM) after 1 year and 3 years were: 9.1 % (95 % CI: 4.2 - 16.2 %) and 11.7 % (95 % CI: 5.9 - 19.5 %) with a relapse incidence (RI) of 31.3 % (95 % CI: 22 - 41.1 %) and 37.9 % (95 % CI: 27.6 - 48.1 %) after 1 year and 3 years respectively.
Pts responding to conventional therapy (CR/PR) showed 1-year and 3-year PFS rates of 73.3 % (95 % CI: 57.7 - 83.8 %) and 63.4 % (95 % CI: 47.2 - 75.8 %), respectively, compared to non-responders who had PFS rates of 43.4 % (95 % CI: 24.9 - 60.6 %) and 34.7 % (95 % CI: 17.5 - 52.6 %), respectively. One-year and 3-year OS rates for responders were 79.1 % (95 % CI: 64.6 - 88.1 %) and 65.3 % (95 % CI: 49.6 - 77.1 %) and 55.3 % (95 % CI: 35.7 - 71.2 %) and 41.9 % (95 % CI: 22.8 - 59.9 %) for non-responders, respectively.
Median follow-up of 27 pts after auto SCT (median age 37 years, range 23-67; female 10 pts) was 5 years (95 % CI: 3 - 8.4 years). One-year and 3-year PFS rates were 61.1 % (95 % CI: 35.3 - 79.2 %) and 38.9 % (95 % CI: 17.5 - 60 %), respectively. The corresponding OS rates were 81.2 % (95 % CI: 60.5 - 91.7 %) and 63.5 % (95 % CI: 41.3 - 79.3 %), respectively.
Conclusions
In this large cohort of Asian and European pts, we demonstrate that allo HSCT is an effective and potentially curative treatment option for HSTCL even in pts unresponsive to chemotherapy. Half of the pts responding to conventional chemotherapy and more than one-third of pts with PD prior to allo HSCT achieved long-term survival which seems clearly better than after any other treatment reported so far. The smaller cohort of pts after auto SCT also showed promising survival rates. However, more pts relapse with time, and selection bias has to be taken into account.
Allo HSCT should be an option to all transplant-eligible pts with HSTCL as first-line treatment.