High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

Abstract

BACKGROUNDOutcome data were analyzed for 27 patients who were affected with recurrent or newly diagnosed high‐risk brain tumors and who underwent high‐dose chemotherapy with triethylenethiophosphoramide (thiotepa) and etoposide in addition to autologous stem cell transplantation between May 1992 and September 2002.METHODSFifteen males and 12 females (median age, 11 years) were included in the study. Twelve patients had newly diagnosed high‐risk brain tumors, and 15 patients had recurrent brain tumors. The conditioning regimen consisted of thiotepa 900 mg/m2 and etoposide 1500 mg/m2 over 3 days starting on Day −5. Stem cell rescue was performed using bone marrow (BM) in 8 patients, peripheral blood stem cells (PBSCs) in 18 patients, and BM and PBSCs in 1 patient.RESULTSFor the BM group, neutrophil (PMN) engraftment was achieved on Day +14 (median value), whereas platelet (PLT) engraftment was achieved on Day +68 (median value). One patient did not achieve PLT engraftment. For the PBSC group, the PMN engraftment was achieved on Day +10.0 (median value), and the PLT engraftment was achieved on Day +15.5 (median value). Transplantation‐related toxicity (evaluated using the Bearman score) included Grade 2–3 mucositis in 16 patients, Grade 1 kidney toxicity in 6 patients, Grade 1 liver toxicity in 6 patients, and Grade 2 liver toxicity in 1 patient. Transplantation‐related mortality was observed in 1 patient (3.6%), who died of Candida pneumonia. The 3‐year overall survival (OS) rate was 44.6%, and the 3‐year event‐free survival (EFS) rate was 31%. There was a statistically significant difference in OS and EFS rates for patients who underwent ASCT and achieved complete remission compared with patients who had measurable disease.CONCLUSIONSThe results of the current study suggest that high‐dose chemotherapy followed by ASCT may be beneficial for patients who achieve complete remission before ASCT, whereas for other patients, new strategies are required. Cancer 2004. © 2004 American Cancer Society.

Stem cell transplantation in children with infantile osteopetrosis is associated with a high incidence of VOD, which could be prevented with defibrotide

“…But pediatric conditioning regimens containing thiotepa were not reported to have an exceedingly high incidence of VOD. [30][31][32][33] Most recently a treatment regimen consisting of cyclophosphamide, thiotepa and carboplatin was assessed for the occurrence of VOD in adults. The calculated plasma concentration-time curves (AUCs) for cyclophosphamide and its activated metabolites showed that the incidence of VOD was rather linked to bioactivated cyclophosphamide than to the administration of thiotepa.…”

Neurotoxicity of chemotherapeutic and biologic agents in children with cancer

“…Intrathecal administration has resulted in myelopathy [28]. Most recent studies do not report any significant neurologic toxicities associated with treatment [29][30][31][32][33].…”

Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study

“…The survival rate was reported as a broad range, 5-54%, by studies done in various different situations with regard to pre-transplant conventional chemotherapy, conditioning regimens, disease status prior to HDCT, and adjuvant therapy. Some studies did not separate recurrent medulloblastoma from high-risk medulloblastoma or other brain tumors types in their study group (8, 12). Grururangan et al (13) reported a 3-yr overall survival rate of 14% in recurrent medulloblastoma patients who underwent HDCT/ASCT and received no irradiation before relapse, while no survival was found in those who underwent HDCT/ASCT receiving irradiation before relapse and in those who did not undergo HDCT/ASCT and received only standard SC.…”

“…Fagioli et al (12) reported that patients with CR status following a poor prognosis brain tumor had a survival rate of 50.6% compare to 19.6% for those without CR status. Cheuk et al (14) reported that long-term survival in CR patients before HDCT was 63% (5 out of 8 CR patients survived), but that 5 PR patients all died in the study of single transplantation in high-risk or recurrent CNS tumors.…”

“…Some studies reported that patients with PR status before HDCT would die eventually from PD since the treatment of HDCT cannot eradicate their residual malignancies (12). The recent study by Cheuk et al reported that 5 patients with PR disease status before HDCT, who had a median 8-month disease free period, did not survive a long-term (12, 14).…”