Treatment outcome of relapsed/refractory primary central nervous system diffuse large B-cell lymphoma: a single-center experience of autologous stem cell transplantation

Abstract

No salvage treatment strategy has been established for relapsed or refractory primary central nervous system lymphoma (PCNSL). We compared treatment outcomes of patients who underwent salvage chemotherapy with or without autologous stem cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were histologically diagnosed with diffuse large B-cell lymphoma. All patients relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were refractory to high-dose MTX. Patients were treated with salvage chemotherapy, such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high-dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by ASCT was performed if patients were eligible for ASCT after salvage treatment. Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose MTX. Despite the important difference that ICE/D was used predominantly for early relapsed or refractory patients, the two salvage treatments produced similar overall response rates [84.4 % (38/45) for ICE/D and 81.3 % (13/16) for high-dose MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received salvage chemotherapy alone. The median progression-free survival of patients who underwent ASCT (19.5 months) was significantly better than that of patients who did not receive ASCT (6.7 months, P = 0.023). Multivariate analysis showed that refractoriness to initial treatment and no ASCT were significantly associated with poor survival outcome. Our study suggested that the combination of ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible salvage treatment option for relapsed or refractory PCNSL, and that high-dose chemotherapy containing thiotepa and busulfan followed by ASCT may be effective for patients with a favorable toxicity profile.

The role of autologous stem cell transplantation in primary central nervous system lymphoma

“…This is of crucial importance if we consider that only 40% of patients ,70 years old with relapsing/refractory PCNSL currently receive HDC/ASCT. 19 The gap in results with conventional-dose salvage and HDC/ASCT are less impressive when comparing similarly selected populations. Moreover, the promising results yielded with salvage HDC/ASCT should be taken into account with caution considering that this strategy is associated with relevant TRM and severe neurotoxicity in elderly or previously irradiated patients.…”

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

“…However, almost 50% of patients relapse within the first two years after diagnosis, and one-third become refractory to conventional chemotherapy [10][11][12]. Salvage treatment options for relapsed/refractory PCNSL include high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) or WBRT [13][14][15]. However, responses to those treatments are usually not durable, and ASCT cannot be used for frail elderly patients.…”

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen

“…Despite data that support the use of HDC/ASCT in patients with NHL involving the CNS as both post-remission consolidation 5,6,8,[10][11][12][13][14][15][16][17][18][21][22][23][24][25][26] and in the relapsed/refractory setting, 8,9,19,20,[28][29][30][31] several unanswered questions remain in regards to ideal patient candidates, optimal conditioning, and timing of transplant. Furthermore, the efficacy and toxicity compared to WBRT or non-myeloablative chemotherapy is still incompletely characterized.…”