High-dose Chemotherapy with Thiotepa, Busulfan, and Cyclophosphamide Followed by Autologous Stem Cell Transplantation in Central Nervous System Lymphoma

Summary

The involvement of the central nervous system (CNS) by non-Hodgkin lymphoma (NHL) has carried a poor prognosis. For both of primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), high-dose methotrexate (HD- MTX) based chemotherapy and combined modality have significantly improved the previously poor response rates and prognosis. However, in PCNSL, relapse rates have remained high, with only 20% to 30% patients achieving a durable long-term remission after HD-MTX. The combination with whole-brain radiotherapy (WBRT) has resulted in higher disease-free and overall survival rates, but it has also been associated with severe neurotoxicity. Patients with SCNSL fare the worst, typically succumbing to disease within median 2.5 to 4 months with 1-year survival rates of only 25%. Because of these dismal outcomes, intensification of the high-dose chemotherapy (HDC)with autologous stem cell transplantation (autoSCT) has been explored for PCNSL and SCNSL as salvage treatment in patients with refractory or relapsed disease, and as consolidation after primary chemotherapy, replacing or preceding WBRT. Thiotepa, busulfan, and cyclophosphamide (TBC) have significant penetration of blood-brain barrier as shown in several pharmacokinetic studies. Thus, combination of these 3 agents was proposed as one high-dose chemotherapy regimen to achieve therapeutic concentrations in the lymphoma tissue in chemotherapy sanctuaries, like cerebrospinal fluid (CSF), meninges and eyes. eyes. Several studies have shown promising results and favorable long-term toxicity profiles with this combination. However, the relatively rarity of this tumor precludes rapid completion of large-scale phase III trial and, therefore, our reliance on the results of well-designed phase II trials is critical. Therefore, we evaluate the efficacy and toxicity of thiotepa, bulsulfan, and cyclophosphamide as a conditioning for autologous stem cell transplantation in patients with PCNSL and SCNSL.

Timeline

Start

2015-06-01

Primary completion

2024-09-30

Completion

2024-09-30

Drugs

Indications