BACKGROUND: Patients with advanced malignancies in non-complete remission (CR) have a dismal prognosis after HLA-matched hematopoietic stem cell transplantation (HSCT). T-cell-replete HLA-haploidentical HSCT has remarkable anti-leukemia/tumor effects on these patients, but also a high risk of severe/extensive graft-versus-host disease (GHVD). Post-transplantation cyclophosphamide (PTCY) is regarded as a GVHD-specific immunosuppressant in adults, but its feasibility is unknown in children. METHODS: We performed a prospective feasibility study of PTCY at 50 mg/kg on day 3 for children with advanced leukemias or malignant solid tumors: refractory to chemotherapy or relapsed after conventional allogeneic HSCT. Conditioning consisted of fludarabine (180 mg/m2) and melphalan (140-210 mg/m2). RESULTS: Long-term engraftments were achieved in 11 patients (73.3%) after bone marrow transplantation (BMT, n = 13) or peripheral blood (PB) stem cell transplantation (n = 2). The incidence of severe acute GHVD was 25.0% and that of extensive chronic GVHD 0.0% after evaluable BMT. CR was achieved in 6/15 and partial response in 4/15 as the best response. Finally, 11/15 experienced disease progression/relapse, 2/15 suffered treatment-related mortality without evidence of disease, and 2/15 are alive in continuous CR. CONCLUSIONS: PTCY is feasible in children; however, for a better outcome in such patients with advanced malignancies, some modifications are anticipated.
BACKGROUND:Patients with advanced malignancies in non-complete remission (CR) have a dismal prognosis after HLA-matched hematopoietic stem cell transplantation (HSCT). T-cell-replete HLA-haploidentical HSCT has remarkable anti-leukemia/tumor effects on these patients, but also a high risk of severe/extensive graft-versus-host disease (GHVD). Post-transplantation cyclophosphamide (PTCY) is regarded as a GVHD-specific immunosuppressant in adults, but its feasibility is unknown in children. METHODS: We performed a prospective feasibility study of PTCY at 50 mg/kg on day 3 for children with advanced leukemias or malignant solid tumors: refractory to chemotherapy or relapsed after conventional allogeneic HSCT. Conditioning consisted of fludarabine (180 mg/m2) and melphalan (140-210 mg/m2). RESULTS: Long-term engraftments were achieved in 11 patients (73.3%) after bone marrow transplantation (BMT, n = 13) or peripheral blood (PB) stem cell transplantation (n = 2). The incidence of severe acute GHVD was 25.0% and that of extensive chronic GVHD 0.0% after evaluable BMT. CR was achieved in 6/15 and partial response in 4/15 as the best response. Finally, 11/15 experienced disease progression/relapse, 2/15 suffered treatment-related mortality without evidence of disease, and 2/15 are alive in continuous CR. CONCLUSIONS:PTCY is feasible in children; however, for a better outcome in such patients with advanced malignancies, some modifications are anticipated.
Authors: Nicolas J Llosa; Kenneth R Cooke; Allen R Chen; Christopher J Gamper; Orly R Klein; Elias T Zambidis; Brandon Luber; Gary Rosner; Nicholas Siegel; Mary Jo Holuba; Nancy Robey; Masanori Hayashi; Richard J Jones; Ephraim Fuchs; Matthias Holdhoff; David M Loeb; Heather J Symons Journal: Biol Blood Marrow Transplant Date: 2017-08-12 Impact factor: 5.742
Authors: Xiaoou Zhou; Gianpietro Dotti; Robert A Krance; Caridad A Martinez; Swati Naik; Rammurti T Kamble; April G Durett; Olga Dakhova; Barbara Savoldo; Antonio Di Stasi; David M Spencer; Yu-Feng Lin; Hao Liu; Bambi J Grilley; Adrian P Gee; Cliona M Rooney; Helen E Heslop; Malcolm K Brenner Journal: Blood Date: 2015-05-14 Impact factor: 22.113
Authors: Orly R Klein; Jessica Buddenbaum; Noah Tucker; Allen R Chen; Christopher J Gamper; David Loeb; Elias Zambidis; Nicolas J Llosa; Jeffrey S Huo; Nancy Robey; Mary Jo Holuba; Yvette L Kasamon; Shannon R McCurdy; Richard Ambinder; Javier Bolaños-Meade; Leo Luznik; Ephraim J Fuchs; Richard J Jones; Kenneth R Cooke; Heather J Symons Journal: Biol Blood Marrow Transplant Date: 2016-11-22 Impact factor: 5.742
Authors: Rohtesh S Mehta; Shernan G Holtan; Tao Wang; Michael T Hemmer; Stephen R Spellman; Mukta Arora; Daniel R Couriel; Amin M Alousi; Joseph Pidala; Hisham Abdel-Azim; Ibrahim Ahmed; Mahmoud Aljurf; Medhat Askar; Jeffery J Auletta; Vijaya Bhatt; Christopher Bredeson; Saurabh Chhabra; Shahinaz Gadalla; James Gajewski; Robert Peter Gale; Usama Gergis; Peiman Hematti; Gerhard C Hildebrandt; Yoshihiro Inamoto; Carrie Kitko; Pooja Khandelwal; Margaret L MacMillan; Navneet Majhail; David I Marks; Parinda Mehta; Taiga Nishihori; Richard F Olsson; Attaphol Pawarode; Miguel Angel Diaz; Tim Prestidge; Muna Qayed; Hemalatha Rangarajan; Olle Ringden; Ayman Saad; Bipin N Savani; Sachiko Seo; Ami Shah; Niketa Shah; Kirk R Schultz; Melhem Solh; Thomas Spitzer; Jeffrey Szer; Takanori Teshima; Leo F Verdonck; Kirsten M Williams; Baldeep Wirk; John Wagner; Jean A Yared; Daniel J Weisdorf Journal: Blood Adv Date: 2019-05-14