High-dose Thiotepa as Consolidation Therapy With Autologous Hematopoietic Stem Cell Transplantation for High-risk Ewing Family Tumors

Abstract

High-dose therapy (HDTx) with autologous stem cell rescue has been widely applied in very-poor-risk pediatric solid tumors. Promising data have become available with the use of high-dose busulfan, whereas high-dose (HD) thiotepa is less commonly used. We report retrospectively our single-institution experience from 1986 to 2012 of single and tandem HDTx with special emphasis on HD-thiotepa as the backbone of HD regimen in Ewing family tumors, including all 24 patients in the Helsinki University Hospital referral area in population-based fashion (Ewing sarcoma 9, Askin tumor 9, peripheral neuroectodermal tumor 6). The 10-year overall survival for the entire cohort was 0.73±0.01. Thirteen out of the 24 underwent HDTx (10 single, 3 tandem). The HDTx regimen consisted of HD-thiotepa (900 mg/m), VP16, and carboplatin. Additional HD-melphalan and total body irradiation were used in the tandem regimens. There was no toxic mortality. The 5-year event-free survival was 0.73±0.16 for high-risk cases transplanted in 1CR. In the relapse group, 1 out of the 3 survived. Radiotherapy to axial sites was given safely in combination with HD-thiotepa in all 3 patients. Thiotepa-based HDTx approach resulted in an encouraging outcome without toxic mortality for high-risk patients. HD-thiotepa merits further studies in larger controlled series.

Role of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for Children and Young Adults with Relapsed Ewing’s Sarcoma: A Systematic Review

“…The OS at 2 years for the 2 relapsed patients in the former study was 50% (CC followed by HDCT), and it was 66% at three years for 3 relapsed patients who were in CR (after receiving CC) prior to HDCT/ASCT in the later study. Jahnukainen et al [ 24 ] noted that the only relapsed ES patient in their study who received thiotepa-based HDCT following CC survived for 8.5 years. In the same study, the cumulative OS for 3 patients with relapsed Ewing's family of tumors (primitive neuroectodermal tumors and Ewing's sarcoma) at 2 years was 100% ( Table 2 ).…”

“…Patients in Graham-Pole et al [ 21 ] did exceptionally poor possibly because of lack of usage of CC prior to HDCT. The three patients with relapsed EFT (including one patient with relapsed ES) along with patients with advanced primary ES in Jahnukainen et al [ 24 ] did exceptionally well on thiotepa HDCT regimen, the reasons not being very clear.…”

Single‐centre study reports a 84% five‐year overall survival rate for paediatric solid tumours

“…The second most common indication was metastatic neuroblastoma, a well‐established indication. High‐dose chemotherapy was also administered to patients with soft tissue and bone sarcomas and CNS tumours, according to investigational protocols or salvage . Although the use of high‐dose chemotherapy with stem cell rescue is controversial in most paediatric cancers, diseases such as high‐risk neuroblastoma or Hodgkin's disease have demonstrated improved outcomes in clinical trials .…”

Token economy to improve adherence to activities of daily living

“…High-dose chemotherapy and hematopoietic stem cell transplant (HSCT) regimens offer prospects of cure for children and young adults with high-risk and relapsed cancers. [1][2][3][4] However, oncology and HSCT patients are at increased risk of developing treatment-related toxicities such as infections, oral complications, and deconditioning. Bloodstream Infections (BSI) are the most significant cause of mortality in pediatric oncology/HSCT patients, second only to relapse.…”