High-Dose Therapy (HDT) with Autologous Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Poor Prognosis Ewing Family Tumors (EFT).
Authors: Bolotin Ellen , Shakhnovits Marianna , Cooper Laurence , Qian Dajun , Hitt Debbie , Sweetman Robert , Sato Judith , Miser James , Forman Stephen , Rosenthal Joseph 
Published: October 2019

Abstract
Purpose: To evaluate the feasibility and safety of treatment with two cycles of HDT followed by autologous HSCT in patients (pts.) with poor prognosis EFT.
Patients and Methods: A retrospective data review of 20 patients with advanced EFT treated at City of Hope National Medical Center (COH) with two cycles of HDT and HSCT from January 1, 1997 to December 31, 2003 was performed. Eligibility criteria for treatment included: histologically-proven diagnosis of EFT; age less than 35 years old at the date of transplant; Lansky or Karnofsky performance status >70%; left ventricular ejection fraction >50%; normal liver and kidney function. HDT for the first cycle consisted of melphalan (MEL)/carboplatin (CARB) in 9 pts and Mel/busulfan (BU) in 11 pts. HDT for the second cycle consisted of MEL/CARB (n=5); MEL/BU (n=3) and cyclophosphamide/etoposide/CARB (n=5). A descriptive analysis of the safety, rate of recurrence, transplant-related morbidity (TRM) and mortality, event-free survival (EFS) and overall survival (OS) are reported.
Results: Out of 20 eligible patients, 13 (65%) received two cycles of HDT followed by autologous HSCT. Seven (35%) patients did not proceed to a second cycle as planned, of whom 2 (28.5%) patients refused, 2 (28.5%) patients died because of rapidly progressive disease, one (14%) patient died because of idiopathic pulmonary fibrosis, one (14%) patient had previous radiation, and one (14%) patient had renal failure. The median follow-up time for all patients (n=20) was 2.4 years (range 0.1 to 7.8 years). Patients tolerated well the first (n=20) and second (n=13) cycles, with limited and predictable toxicities. Grade 4 adverse events were limited to mucositis and pancytopenia. No TRM was recorded after the first cycle of HDT and HSCT. For the second cycle, there was one death due to rapidly progressive disease. There were no differences in outcome between the various HDT regimens used. A sustained absolute neutrophil count (ANC) of more than 1,000/mm3 for both cycles was achieved at the median of 11 days. A sustained platelet count of more than 50,000/m3 was achieved at a median of 17 to 20 days of first and second cycle. There were no differences in OS rates between patients who had metastatic disease compared to patients without metastatic disease at the time of diagnosis. The Kaplan-Meier estimates of OS and EFS at three years were 45% (CI 0.22, 0.69) and 47% (CI 0.25,0.70), respectively. For patients who have received two cycles of HDT followed by HSCT, the Kaplan-Meier estimates of OS and EFS at three years were 58% (CI 0.30, 0.86) and 58% (CI 0.30, 0.86), respectively.
Conclusion: Our data suggests that dose-intensification with two cycles of HDT and HSCT is feasible and relatively safe, with low and acceptable treatment related morbidity and mortality. Adding a second course of therapy does not impair engraftment. Both OS and EFS compare favorably with previously published reports. HDT with HSCT may improve outcome in patients with poor prognosis EFT. Further studies are required to establish the optimal regimen for HDT.