High-dose chemotherapy with hematopoietic stem cell transplantation in adults with bone marrow relapse of medulloblastoma: report of two cases

Abstract

Summary:Extraneural relapses of medulloblastoma are associated with a very poor outcome. We present two cases of young adults who developed bone marrow metastases after treatment of medulloblastoma. A very good response to a sequentially scheduled combination of carboplatin and etoposide was observed. Then, high-dose chemotherapy was delivered consisting of busulfan and thiotepa followed by infusion of autologous hematopoietic stem cells. Toxicity of the conditioning regimen was acceptable. The patients remained free of disease 20 and 27 months from the time of relapse, respectively. Further studies are needed to evaluate the impact of high-dose chemotherapy in terms of survival of such patients. Keywords: adult medulloblastoma; metastases; chemotherapy; autologous stem cell transplantation Medulloblastoma, a malignant tumor originating in the cerebellum, generally occurs in the first decade of life. It is a rare disease in the adult population and represents less than 1% of adult brain tumors. Extraneural relapses of medulloblastoma represent 7 to 13% of recurrences and are associated with a very poor outcome. 1 Encouraging preliminary data have been reported in children with recurrent malignant brain tumors receiving high-dose chemotherapy with autologous bone marrow rescue. 2,3 We report two young adults who underwent autologous hematopoietic stem cell transplantation for bone marrow relapse of medulloblastoma. Case reports Patient 1In July 1995, a non-metastatic cerebellar medulloblastoma was diagnosed in a 22-year-old man. The tumor was totally resected and cranio-spinal radiation therapy was given postoperatively. Fifteen months later the patient complained of left hip pain. A pelvic magnetic resonance (MR) scan revealed diffuse low intensity signals on T1-weighted images, high intensity signals on T2-weighted images in the bone marrow of the left acetabulum and the body of the left ilium with enhancement after gadolinium administration ( Figure 1a). An open biopsy of the left ilium and a bone marrow biopsy of the right posterior iliac crest revealed marrow involvement with metastatic medulloblastoma cells. No evidence of recurrent tumor within the central nervous system was demonstrated. Combination chemotherapy consisting of carboplatin (160 mg/m 2 /day) and etoposide (100 mg/m 2 /day) for 5 days was administered. Cycles were repeated at 4 weekly intervals. The patient was symptom-free after the first course of chemotherapy. Bone marrow biopsy was normal after the second course of chemotherapy. He received a total of five courses of carboplatin-etoposide. There were no episodes of febrile neutropenia. The main toxicities were nausea and myelosuppression. After the fifth course of chemotherapy, MR revealed marked improvement in the left ilium and left acetabulum bone marrow signals (Figure 1b). Cytapheresis was performed after a 3 g/m 2 cyclophosphamide infusion followed by G-CSF administration, leading to the collection of 2 × 10 6 CD34 cells/kg (before cryopreservation) and 8.5 × 10 4 CFU-GM/kg (after ...

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

“…14,[20][21][22] One case report of two patients has shown that high-dose chemotherapy consisting of busulfan and thiotepa followed by infusion of autologous hematopoietic stem cells produced disease-free survival times of 20 and 27 months after bone marrow relapse of medulloblastoma. 15 High-dose carboplatin, thiotepa and etoposide with autologous stem-cell rescue have also shown some activity against recurrent medulloblastoma. 11 High-dose chemotherapy is still thought to be an experimental procedure that has yet to show a clear advantage over conventional chemotherapy in adult recurrent medulloblastoma.…”

“…9 Promising results with HDCT/ASCT prompted us to use this form of therapy for young adults with recurrent medulloblastoma, who were otherwise healthy and had no possibility of cure with conventional dose therapy. [10][11][12][13][14][15] Here, we report the outcomes of six adults who underwent HDCT (cyclophosphamide, carboplatin, thiotepa, etoposide) with ASCT for medulloblastoma relapse. Table 1 lists the clinical profile of patients 1-6.…”

High-Dose Chemotherapy in Childhood Brain Tumors

“…Nitrosurea-based protocols did produce impressive responses [26,55], but the pulmonary toxicity was too high [55,56]. The thiotepa/busulfan protocols have also been used successfully in 3 adults with metastatic relapse of medulloblastoma [33,57,58]. Cyclophosphamide appeared to be particularly effective in this group of tumors.…”

High-dose chemotherapy with autologous stem cell support in an adult with bone marrow relapse of medulloblastoma

“…High-dose chemotherapy with autologous stem cell support in an adult with bone marrow relapse of medulloblastoma Millot et al 1 recently reported the effectiveness of treatment strategies including chemotherapy with etoposide and carboplatin followed by high-dose chemotherapy with peripheral blood stem cell transplantation in two adults with recurrent extraneuronal medulloblastoma (patients still in complete remission 20 and 27 months after treatment). We describe a case of an adult with medulloblastoma treated with the same regimen for bone and bone marrow metastasis involvement.…”