High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study

Abstract

In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.

Thiotepa‐based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched‐pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…In the past decade, radiation‐free conditioning regimens have been consistently shown to confer a potent anti‐leukemia effect with concomitant avoidance of the major toxicities associated with TBI . In recent years, thiotepa, an alkylating agent initially introduced nearly six decades ago, has been gaining acceptance as effective therapy for primary and secondary central nervous system (CNS) lymphomas, in concert with additional agents . Indeed, thiotepa‐based radiation‐free conditioning has been used successfully in various hematologic malignancies .…”

Primary CNS Lymphoma in the Elderly: The Challenge

“…Because of the high risk and associated toxicity, this treatment is usually offered to younger patients (< 65 years) with a good performance status. Schorb et al [3] reported retrospectively on the outcome of 52 patients with PCNSL aged ≥65 years who received thiotepa-based conditioning with ASCT (29% as first-line treatment). The conclusion was that in selected elderly patients, this is an effective, safe treatment if conducted at experienced centers.…”

“…Consequently, 60 years of age is frequently used as a cutoff to define the elderly population of PCNSL patients. Nevertheless, several studies have shown that fit patients above the age of 60 years can tolerate high-dose chemotherapy and even an intensive up-front treatment with a high overall response rate reported (range: 60–89%) including a proportion of long-term survivors (Table 1) [3-17]. Yet, many clinical trials exclude patients above the age of 70 years [11, 18], and about a quarter of PCNSL patients older than 70 years who survive more than 3 months from diagnosis do not receive chemotherapy at all [19].…”

“…Fourteen studies were dedicated to elderly patients [4, 5, 7, 9, 12, 24-33], and 7 studies accrued adult patients of all ages but contained information on outcome of the elderly subgroup [6, 13-16, 34, 35]. One retrospective study [3] described the outcome of thiotepa-based chemotherapy with ASCT administered to 52 elderly lymphoma patients, of whom 15 were PCNSL treated by this protocol as first-line approach. Nine of the 14 studies dedicated to elderly patients [7, 12, 25, 26, 28-32] were retrospective, and 4 were phase II studies [4, 5, 9, 27], with one of them designed as a randomized phase II study [4].…”

Guidelines for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma

“…Performance status often improves following initial therapy which may allow subsequent intensification of therapy. Moreover, both intensive multi‐agent induction and high dose therapy with autologous stem cell transplant (HDT‐ASCT) approaches are feasible in selected older patients, including some aged >70 years (Schorb et al , 2017a). No validated comorbidity assessment exists to guide treatment choices.…”