title: Long-Term Follow-Up after Reduced-Intensity Conditioning and Stem Cell Transplantation for Childhood Nonmalignant Disorders.
abstract: Reduced-intensity conditioning (RIC) before hematopoietic stem cell transplantation (HCT) in children could result in fewer complications during follow-up compared with myeloablative regimens. Hence, many RIC regimens are under investigation, but long-term follow-up is essential. We describe late follow-up beyond 2 years post-HCT in 43 children with nonmalignant disorders who underwent related or unrelated donor (56%) HCT on a multicenter study using a RIC regimen (alemtuzumab, fludarabine, and melphalan) followed by bone marrow (n = 30), peripheral blood (n = 3), or umbilical cord blood (n = 10) HCT for immune dysfunction, bone marrow failure, metabolic disorders, or hemoglobinopathy. Recipients (median age, 7.5 years; range, 3 to 26) underwent HCT 2 to 8 years (median, 3.1 years) before this report. Full donor (67%) or stable mixed chimerism (33%) was noted without late graft rejection. Five patients (12%) required systemic immunosuppression therapy (IST) beyond 2 years post-HCT for graft-versus-host disease (GVHD); 2 patients died 38 and 79 months later, whereas the others improved, enabling an IST wean. Overall, 17 complications were documented in 10 patients (23%). Complications not related to GVHD included hypothyroidism (n = 2), low grade neoplasms (n = 2), and delayed puberty (n = 1). One patient with GVHD had ovarian failure; all other postpubertal females resumed normal ovarian function. Twenty-seven of 28 school-age recipients were functioning at grade level. RIC HCT recipients thus had few regimen-related toxicities during long-term follow-up. However, objective long-term follow-up is still necessary to identify complications so timely intervention may be planned.
authors.affiliation: Division of Pediatric Hematology Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Madden
authors.affiliation: Division of Pediatric Hematology Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hayashi
authors.affiliation: Pediatric Blood & Marrow Stem Cell Transplant Program, Methodist Children's Hospital of South Texas, San Antonio, Texas.
authors.forename: Ka Wah
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: Pediatric Blood and Marrow Transplant Program, Phoenix Children's Hospital, Phoenix, Arizona.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Douglas
authors.affiliation: Pediatric Hematology/Oncology, All Children's Hospital, St. Petersburg, Florida.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.affiliation: Pediatrics-Hematology, Oncology and Stem Cell Transplantation, Lurie Children's Hospital, Chicago, Illinois.
authors.forename: Sonali
authors.initials: S
authors.lastname: Chaudhury
authors.affiliation: Division of Pediatric Hematology/Oncology, Riley Hospital for Children, Indianapolis, Indiana.
authors.forename: Paul
authors.initials: P
authors.lastname: Haut
authors.affiliation: Division of Pediatric Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.affiliation: Division of Pediatric Hematology/Oncology, Levine Children's Hospital, Charlotte, North Carolina.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gilman
authors.affiliation: Division of Pediatric Hematology Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Murray
authors.affiliation: Division of Pediatric Hematology Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: shenoy@wustl.edu.
authors.forename: Shalini
authors.initials: S
authors.lastname: Shenoy
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006453:Hemoglobinopathies / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: Childhood nonmalignant disorders; Late complications; Reduced-intensity conditioning; Stem cell transplantation