Double‐conditioning regimen consisting of high‐dose thiotepa and melphalan with autologous stem cell rescue for high‐risk pediatric solid tumors: A second report

Abstract

Background: Pediatric patients with high-risk, relapsed, or refractory solid tumors have a poor prognosis. We have previously reported a dose-finding experience of high-dose chemotherapy consisting of thiotepa and melphalan ("double-conditioning regimen"). Using doses derived from that study, we have treated patients since 2005. We now report a retrospective review of patients treated by this fixed dose. Procedure:We reviewed 50 patients (median 4 years; range 0-15 years) with high-risk or relapsed/refractory solid tumors treated by this dose-fixed, double-conditioning regimen from April 2005 to May 2014. Doses were thiotepa 800 mg/m 2 and melphalan 280 mg/m 2 for children ≥2 years of age, and 32 mg/kg and 6 mg/kg, respectively, for children <2 years of age. Further, doses were reduced according to creatinine clearance with poor renal function. Results:Nonhematological toxicity was mainly gastrointestinal-grade 3 mucositis (n = 41) and grade 3-4 diarrhea (n = 10). Neurological, renal, and endothelial cell toxicity and sinusoidal obstruction syndrome were not observed. There were two toxic deaths (interstitial viral pneumonia). This regimen demonstrated antitumor activity against several types of tumors. Although the frequency of gastrointestinal toxicity was high, other severe toxicity was not observed. Conclusions:Our double-conditioning regimen was very well tolerated and demonstrated antitumor activity. We are moving forward with multi-institutional trials now. K E Y W O R D Smelphalan, pediatric solid tumor, stem cell transplantation, thiotepa

Strategy to minimize radiation burden in infants and high‐risk medulloblastoma using intrathecal methotrexate and high‐dose chemotherapy: A prospective registry study in Japan

“…Radiation therapy was simultaneously administered from the beginning of the second chemotherapy course, with a recommended CSI dose of 18 Gy in 12 fractions and a local boost dose of 32 Gy in 20 fractions (total: 50 Gy), and the recommended field for local irradiation was defined as the posterior fossa. After the four courses of chemotherapy, an additional course of HDC with thiotepa and melphalan (the “double‐conditioning regimen”) was recommended, based on a previous report (thiotepa at 200 mg/m 2 and melphalan at 70 mg/m 2 on days –12, –11, –5, and –4) . An additional IT‐MTX dose was administered once during the HDC.…”

“…During the last 20 years, there have been various attempts to develop HDC using thiotepa, although the results in childhood MB have been limited . Moreover, the efficacy and safety of our unique HDC regimen, which we have named the “double‐conditioning regimen,” have been reported for pediatric solid tumors but not for MB . For example, the HDC regimen from the present study included various beneficial characteristics, such as the use of a combination with melphalan, the 5‐day rest between drug administrations, and the continuous infusion of thiotepa.…”

“…-11, -5, and -4). 21,22 An additional IT-MTX dose was administered once during the HDC. The details of the recommended regimens are summarized in Figure 1.…”

“…[32][33][34][35][36][37] Moreover, the efficacy and safety of our unique HDC regimen, which we have named the "double-conditioning regimen," have been reported for pediatric solid tumors but not for MB. 21,22 For example, the HDC regimen from the present study included various beneficial characteristics, such as the use of a combination with melphalan, the 5-day rest between drug administrations, and the continuous infusion of thiotepa. These characteristics may have contributed to the good results in the HR group of patients with…”

Effects of cryotherapy on high‐dose melphalan‐induced oral mucositis in pediatric patients undergoing autologous stem cell transplantation

“…Melphalan (MEL) is an alkylating agent that has been widely used as a conditioning regimen prior to hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies and solid tumors 1‐5 . Oral mucositis (OM) is still one of the major complications of MEL, 6 with an incidence of 30‐40% in adult patients with multiple myeloma receiving high‐dose (ie, ≥140 mg/m 2 ) MEL monotherapy without specific prophylaxis 7,8 .…”