Outcomes of Secondary CNS Lymphoma with Carmustine/Thiotepa Conditioning and Autologous Stem Cell Transplant-a Case Series from Single Center, Saudi Arabia
Authors: Bahaliwah Zakarya , Yahia Alaa Eldein , Alsakkaf Abdullah , Alhalouly Tahani , Alzahrani Kamal , Alsughayir Ammar Hasan , Alnoamani Mohammed S , Alshehri Hassan , Alshehry Nawal F , Alhumaid Muhned , Marei Mohammed , Motabi Ibraheem H , Tailor Imran K 
Published: December 2024

Background:
Secondary Central Nervous System (CNS) Lymphoma (SCNSL) is very rare and refers to lymphoma that has involved CNS concurrently or CNS relapse during or after frontline chemotherapy presenting with or without systemic lymphoma. Despite its dismal prognosis with poor survival, there has been an advancement in the recent years (J P Alderuccio Blood 2023). There is no standard of care regarding chemotherapy however induction with methotrexate-based regimen, and consolidation with autologous stem cell transplant has been the usual treatment approach (Cwynarski K BjH 2022). Chimeric Antigen Receptor T cell (CAR T) therapy also showing promising outcomes (A P Boardman Hematol Oncol 2023). There has been variation in usage of conditioning regimen, however carmustine/thiotepa is reported to be safe and effective based on data from primary CNS lymphoma (Scordo JAMA 2021). There has limited data on outcome of these group of patients from middle east, we present here our experience of such patients who were treated initially with methotrexate based regimen followed by carmustine/thiotepa based autologous stem cell transplant
Methods:
This is a retrospective observational, single center experience s from King Fahad Medical City, Saudi Arabia. Total of over 190 Diffuse Large B Cell Lymphoma (DLBCL) patient screened between Jan 2018 and November 2023 and patients with SCNSL at presentation or relapse who underwent stem cell transplant were included. Using computerized hospital system “EPIC”, patient files have been accessed. Response assessment was done using PET and CT scan as well as MRI. The primary end points were OS and PFS. Secondary end points were engraftment and transplant related mortality.
Results:
Total of 5 patients included, 4 of them had diffuse large b cell lymphoma and one had Burkitt's lymphoma. Median age was 38 (Range 28, 42). 3/5 patients has CNS involvement only at relapse with no systemic disease, salvaged with methotrexate/cytarabine/thiotepa (MATRIX), however one had concomitant CNS and systemic disease at first presentation managed with rituximab, cyclophosphamide, vincristine, prednisolone, doxorubicin (RCHOP) and high dose methotrexate (HDMTX) and Etoposide, Cytarabine, Prednisolone, Cisplatin (ESHAP). One patient with relapsed burkitt's lymphoma with CNS involvement was salvaged with Ibrutinib/Etoposide/Doxorubicin/Dexamethasone (TEDDI R). 4/5 patients achieved complete response and one had partial response prior to transplant. 4/5 (80%) patients underwent autologous stem cell transplant, however one underwent allogeneic stem cell transplant due to failed collection. All autologous stem cell transplant patients received carmustine/thiotepa conditioning. All patients engrafted and were discharged home by Day 24. 4/5 (80%) patients had negative PET scan at 6 weeks post-transplant. Two patients died due to progressive disease while one due to progressive fungal infection (patient who underwent allogeneic transplant) but was in remission. Despite the history of dismal outcome of this disease, at 1 year PFS was 40% and OS was 40%. Two patients (40%) remained in remission for more than a year, and one alive for more than 5 years.
Conclusion:
SCNSL is a difficult to treat condition with poor outcomes. Our study showed that one third of patients could achieve long term survival with possible cure with aggressive salvage and autologous stem cell transplant, using carmustine/thiotepa conditioning, which is effective and well tolerated with no treatment related mortality in our study and faster engraftment. However, with availability of novel bispecific antibodies, CAR T cells, treatment paradigm is ever evolving.