title: Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Children with Advanced Acute Leukemia with Fludarabine-, Busulfan-, and Melphalan-Based Conditioning.
abstract: Post-transplantation cyclophosphamide (PTCY) therapy has made haploidentical transplantation a global reality in adults, but the literature is largely silent on the feasibility of this approach in children. We conducted a prospective study of 20 patients (median age, 12 years; range, 2-20 years) with advanced acute leukemia to evaluate the feasibility of PTCY-based haploidentical peripheral blood stem cell (PBSC) transplantation in children. The conditioning regimen comprised fludarabine, i.v. busulfan, and melphalan (Flu-Bu-Mel). PTCY on days +3 and +4 was followed by mycophenolate mofetil for 14-21 days and cyclosporine for 60 days. Thirteen patients (65%) had refractory or relapsed myelogenous leukemia, and the remainder had high-risk lymphoblastic leukemia. Prompt engraftment was noted at a median of 14 days, with full donor chimerism by day +28. The cumulative incidence of acute and chronic graft-versus-host disease was 35% and 5%, respectively. Nonrelapse mortality at 1 year was 20%. The incidence of disease progression was 25.7%. The actuarial overall survival at 2 years was 64.3% (95% confidence interval, 53.4%-75.2%). Our data suggest that Flu-Bu-Mel-based conditioning followed by PTCY-based haploidentical PBSC transplantation with reduced duration of immunosuppression is feasible in pediatric patients with advanced leukemia.
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India; Manashi Chakrabarti Foundation, Kolkata, India. Electronic address: drsaritaranij@gmail.com.
authors.forename: Sarita Rani
authors.initials: SR
authors.lastname: Jaiswal
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Chakrabarti
authors.affiliation: Manashi Chakrabarti Foundation, Kolkata, India; Apollo Gleneagles Hospital, Kolkata, India.
authors.forename: Sumita
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
authors.forename: Sneh
authors.initials: S
authors.lastname: Bhargava
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, CSIR-CRRI, New Delhi, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Donnell
authors.affiliation: Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India; Manashi Chakrabarti Foundation, Kolkata, India.
authors.forename: Suparno
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D064591:Allografts; D002066:Busulfan / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D036102:Peripheral Blood Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan
keywords: Haploidentical; Leukemia; Pediatric; Peripheral blood stem cells; Post-transplantation cyclophosphamide