Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma

Abstract

Summary:In an attempt to improve the dismal prognosis of adults with recurrent medulloblastoma, six patients were treated with aggressive salvage therapy including highdose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). At relapse, all patients underwent surgical debulking followed by HDCT/ASCT and then radiotherapy when possible. The treatment plan included two cycles of HDCT/ASCT; first with cyclophosphamide, etoposide and carboplatin (CECb) and then 2 months later with cyclophosphamide and thiotepa (CT). Three of the six patients received the planned therapy. One patient experienced severe toxicity requiring life-sustaining therapy. This patient developed multi-organ dysfunction including multiple enhancing lesions in both cerebral hemispheres that slowly resolved over several months. Two other patients did not mobilize sufficient stem cells for two ASCT procedures. They received one ASCT conditioned with cyclophosphamide, thiotepa and carboplatin (CTCb). Three of six patients had a complete response (CR); the other three had a partial response (PR). Following the first ASCT, median duration of response was 13.5 months (range 9-29 months) and median survival was 21.5 months (range 12-42 months). There was no treatment-related mortality. We conclude that HDCT/ASCT with CECb-CT or CTCb is active against recurrent medulloblastoma in adults and may be associated with prolonged remissions. Multiple enhancing cerebral lesions on brain MRI early post-HDCT/ASCT may be a consequence of the treatment rather than metastatic disease.

High‐dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system

“…The observed toxicity was less compared with the toxicity reported in older series, with excellent tolerance and no toxic deaths reported. 8,9 In conclusion, the current study supports the use of HDC with ASCT in adults with recurrent embryonal CNS tumors. When compared with conventional cisplatin-based and/or nitrosourea-based chemotherapy regimens, which have previously been shown to be active in this setting, HDC with ASCT results in prolonged TTP and median survival, with acceptable toxicity.…”

“…Three patients died of treatment-related toxicity and several others developed grade 3 and 4 toxicities, including hepatic, cardiac, CNS, renal, and dermatologic toxicities. 2 Zia et al 8 evaluated 6…”

“…8 Abrey et al examined the role of HDC with ASCT in 45 adults with malignant primary brain tumors, 14 of whom had recurrent embryonal tumors. Chemotherapy was carmustine-based, thiotepa-based, or carboplatinbased.…”

“…The use of stem cell rescue could allow use of significantly higher doses of agents shown to be efficacious in the treatment of embryonal CNS tumors, such as cyclophosphamide, cisplatin, carboplatin, carmustine, etoposide, and thiotepa. 7,8 There are limited data regarding the role of HDC with ASCT in adults. Earlier studies have reported a possible benefit, but at the expense of significant toxicity.…”

“…Earlier studies have reported a possible benefit, but at the expense of significant toxicity. 2,8,9 In this single-institution study, we evaluated patients treated with HDC with ASCT and compared their outcomes with those of an historic cohort of patients who received conventionaldose chemotherapy.…”