ASCT With TEAM Conditioning for Lymphoma With High Risk of CNS Relapse
Second Affiliated Hospital, School of Medicine, Zhejiang University
Abstract
In the era of novel therapeutic agents, high-dose conditioning chemotherapy combined with autologous hematopoietic stem cell transplantation (auto-HSCT) remains an important and feasible consolidation strategy for non-Hodgkin lymphoma, especially for high-risk and relapsed/refractory patients. It can effectively prolong progression-free survival and even overall survival in chemotherapy-sensitive lymphoma patients, and its application in domestic clinical practice has become increasingly widespread. With long-term and extensive use of carmustine-based conditioning regimens, their limitations have become increasingly apparent: the drug is expensive and has limited accessibility. Early treatment-related toxicities include mucositis, nausea, vomiting, diarrhea, and hepatotoxicity. Late toxicities include reduced pulmonary diffusion capacity, chronic interstitial pulmonary fibrosis, metabolic syndrome, and cardiovascular complications, all of which have attracted increasing attention. Thiotepa, a cell-cycle-nonspecific alkylating agent, not only inhibits DNA synthesis and kills tumor cells but also readily crosses the blood-brain barrier, has a short half-life and rapid metabolism, and its safety has been widely confirmed in clinical practice. It is an ideal agent for transplant conditioning. In recent years, various thiotepa-based conditioning regimens have been used in auto-HSCT for different types of non-Hodgkin lymphoma, achieving favorable efficacy and safety profiles, and can partially replace the classic BEAM regimen. Investigators at our center observed that among non-Hodgkin lymphoma patients eligible for auto-HSCT, some have involvement at special sites, such as the central nervous system, nerve roots inside or outside the spinal canal, reproductive organs (uterus, ovary, breast, testis), kidney/adrenal gland, and multiple extranodal sites (bone, colorectum), all of which confer a high risk of central nervous system recurrence. Meanwhile, the high cost of thiotepa limits its clinical use. To benefit more patients with CNS-high-risk lymphoma, our center has adjusted the dosage of the existing TEAM regimen. In a 4-year retrospective study, 29 lymphoma patients with involvement at the above sites received modified TEAM conditioning chemotherapy followed by auto-HSCT. With a maximum follow-up of 3 years, 2 patients died of disease progression, 1 patient remained in stable condition after radiotherapy for relapse, and all other patients achieved long-term survival with stable disease. Therefore, our center is applying to conduct a prospective study of this conditioning regimen to obtain more convincing clinical evidence, provide a stronger theoretical basis for auto-HSCT conditioning for more CNS-high-risk lymphoma patients, and explore a more effective, less toxic, and cost reasonable therapeutic strategy. Phase: PHASE2 Status: RECRUITING Conditions: Lymphoma Patients With High-risk of Central Nervous System Relapse Interventions: TEAM regimen (thiotepa, etoposide, cytarabine and melphalan)