Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children

Abstract

Autologous hematopoietic stem cell transplant (AHSCT) has been advocated as a form of salvage therapy for children with high-risk or relapsed brain tumors but only limited data are available currently. We report the outcomes of pediatric brain tumors treated with AHSCT in a quaternary referral center in Hong Kong over 10 years (June 1996-May 2006). Thirteen patients with medulloblastoma (n = 9), cerebral primitive neuroectodermal tumor (n = 1), ependymoma (n = 1), germ cell tumor (n = 1) and cerebellar rhabdoid (n = 1) were transplanted because of tumor residual (n = 1) or recurrence (n = 12). Uniform upfront treatment protocols were adopted according to specific tumor types. Prior to AHSCT, 8 patients (61.5%) achieved complete remission and 5 (38.5%) were in partial remission. Conditioning employed thiotepa 300 mg/m2, etoposide 250 mg/m2)and carboplatin 500 mg/m2 daily for 3 days. Toxicity included mucositis and neutropenic fever in all patients, grade 4 hepatic toxicity in 4 patients (including hepatic veno-occlusive disease in 2 patients) and grade 4 renal toxicity in 1 patient. The 5-year event-free survival was 53.9%. Five patients died of disease recurrence or progression 8-21 months after transplant with a median disease-free period of 8 months post-transplant. One died of transplant-related complications in the early post-transplant period. Seven survived for a median of 5.4 years (maximum follow-up of 9.8 years), with six having Lansky-Karnofsky performance score above 80. All survivors had complete remission before transplant though 2 had leptomeningeal spread. We conclude that AHSCT can achieve long-term survival in children with recurrent brain tumor. However, those with macroscopic residual tumor before transplant cannot be salvaged.

No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

“…Valteau-Couanet et al (16) described two long-term survivors in a group of 15 children receiving an intensive regimen with busulfan and thiotepa, plus surgery and re-irradiation in a nonspecified subgroup. Similarly, Cheuk et al reported only one survivor of recurrent medulloblastoma of 5 patients given CSI at diagnosis, after treatment with high-dose chemotherapy including thiotepa, etoposide, and carboplatin with PBSC rescue (17). Of the children with these same features treated at St. Jude's, Shih et al mention only one survivor treated for recurrent pineoblastoma of a total of 15 children with relapsing medulloblastoma/ primitive neuroecto dermal tumor given a variety of high-dose regimens (18).…”

Specificities of Autologous Haematopoietic Stem Cell Transplantation in Children: A Single Centre Experience

“…Compared to "high-grade" gliomas and ependymomas, AHSCT is known to achieve better results in recurrent, refractory or high-risk medulloblastomas, primitive neuroectodermal tumours of the brain, atypical teratoid rhaboid tumours and germinomas of the central nervous system with disease-free survival of 10-50% [16][17][18]. Nevertheless, dose-dependant therapeutic response of tumours of neuroectodermal origin that was previously reported in these studies did not manifest in our results [2,[19][20][21]. We also observed poor results in rhabdomyosarcoma patients.…”

Training stem cells for treatment of malignant brain tumors

“…For example, patients rely on autologous hematopoietic stem cell transplantation to replenish immune capacity against recurrent cancer after surgery and chemotherapy [49] . Currently, 240 studies on "stem cell therapy of cancer" exist in mostly Phases and specificity; and (3) The vehicle possesses the ability to home in on targets.…”