TY - JOUR
T1 - Reduced-Intensity Allogeneic Stem Cell Transplantation in Children and Young Adults with Ultrahigh-Risk Pediatric Sarcomas
AU - Baird, Kristin
AU - Fry, Terry J.
AU - Steinberg, Seth M.
AU - Bishop, Michael R.
AU - Fowler, Daniel H.
AU - Delbrook, Cynthia P.
AU - Humphrey, Jennifer L.
AU - Rager, Alison
AU - Richards, Kelly
AU - Wayne, Alan S.
AU - Mackall, Crystal L.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the National Institutes of Health (NIH) , National Cancer Institute , Center for Cancer Research . The authors are employees of the United States Government, and as such, this work was done in that capacity. The views expressed do not necessarily represent the views of the National Institutes of Health or the United States Government. The authors thank Ronald E. Gress for his thoughtful insights. We also acknowledge the exhaustive efforts of Natasha Brunson, Keith O’Neil, Leon Schnabel, Joanne Derdak, Barbara Wise, our clinical fellows, and nursing staff. Finally, we express sincere gratitude to our patients and their families.
PY - 2012/5
Y1 - 2012/5
N2 - Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation.
AB - Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation.
KW - Allogeneic stem cell transplantation
KW - Pediatric soft tissue sarcoma
KW - Reduced-intensity transplantation
KW - Solid tumor
UR - http://www.scopus.com/inward/record.url?scp=84859813841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859813841&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2011.08.020
DO - 10.1016/j.bbmt.2011.08.020
M3 - Article
C2 - 21896345
AN - SCOPUS:84859813841
SN - 1083-8791
VL - 18
SP - 698
EP - 707
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 5
ER -