title: Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies.
abstract: Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address: oklein2@jhmi.edu.
authors.forename: Orly R
authors.initials: OR
authors.lastname: Klein
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Buddenbaum
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Noah
authors.initials: N
authors.lastname: Tucker
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Chen
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gamper
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Loeb
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Elias
authors.initials: E
authors.lastname: Zambidis
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Llosa
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Huo
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Nancy
authors.initials: N
authors.lastname: Robey
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Holuba
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Yvette L
authors.initials: YL
authors.lastname: Kasamon
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: McCurdy
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Ambinder
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.affiliation: Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Symons
mesh_terms: D000293:Adolescent; D064591:Allografts; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000628:therapy*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009190:Myelodysplastic Syndromes / Q000628:therapy; D012189:Retrospective Studies; D012306:Risk; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: Acute leukemia; Cyclophosphamide; HLA-haploidentical transplantation; Lymphoma; Myelodysplastic syndrome; Nonmyeloablative bone marrow transplantation