Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning.
Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation.
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina. Electronic address: heather.allewelt@dm.duke.edu.
Heather
H
Allewelt
The EMMES Corporation, Rockville, Maryland.
Jill
J
El-Khorazaty
The EMMES Corporation, Rockville, Maryland.
Adam
A
Mendizabal
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina.
Mahsa
M
Taskindoust
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina.
Paul L
PL
Martin
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina.
Vinod
V
Prasad
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina.
Kristin
K
Page
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Jean
J
Sanders
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina.
Joanne
J
Kurtzberg
D002066:Busulfan / Q000009:adverse effects* / Q000627:therapeutic use; D064419:Chemically-Induced Disorders; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D064420:Drug-Related Side Effects and Adverse Reactions; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D000069451:Long Term Adverse Effects; D019653:Myeloablative Agonists / Q000009:adverse effects; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*
D019653:Myeloablative Agonists; D002066:Busulfan
Busulfan; Late effects; Myeloablative conditioning; Umbilical cord blood transplantation