title: High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: atopy predicts idiopathic diffuse lung injury syndromes.
abstract: The use of high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for children and adolescents with primary refractory and relapsed Hodgkin's disease is increasing. The purpose of this retrospective analysis was to: (1) evaluate the outcome of HDT and AHCT in pediatric patients with Hodgkin's disease, and (2) identify factors that predispose patients to the development of transplantation-related complications. We describe the experiences of 34 pediatric patients from a single institution with primary refractory or relapsed Hodgkin's disease. HDT regimens consisted of cyclophosphamide and etoposide combined with either carmustine, chloroethylcyclohexylnitrosurea, or fractionated total body irradiation. Kaplan-Meier survival predicts that 67% (95% confidence interval [CI] 47%-87%) of patients will be alive and disease-free at 5 years. Nine patients had disease recurrence, of whom 5 relapsed after 1 year (1.5-6.3 years). Five patients succumbed to treatment-related toxicities, of whom 4 died of pulmonary failure. Fifteen patients (44%) developed post-AHCT idiopathic diffuse lung injury syndrome: acute alveolitis (n = 2); diffuse alveolar hemorrhage (n = 2); acute respiratory distress syndrome (n = 2); delayed interstitial pneumonitis (n = 8); and bronchiolitis obliterans (n = 1). The following factors did not predict for the development of a diffuse lung injury syndrome in univariate analysis: prior treatment with bleomycin, pre-HDT pulmonary function tests, and prior thoracic irradiation. Of the patients in our cohort, 44% had a history of atopy (allergic rhinitis and/or asthma). Multivariate logistic analysis revealed that a preexisting history of atopy was highly predictive of idiopathic pulmonary complications (P = .0001, odds ratio = 21, CI 3.6-125). Our experience shows that HDT followed by AHCT results in durable remissions in two thirds of pediatric patients with refractory and relapsed Hodgkin's disease, and a history of atopy is associated with post-AHCT pulmonary complications.
authors.affiliation: Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Stanford University Medical Center, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Frankovich
authors.forename: S S
authors.initials: SS
authors.lastname: Donaldson
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: R M
authors.initials: RM
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: Amylon
authors.forename: M R
authors.initials: MR
authors.lastname: Verneris
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006689:Hodgkin Disease / Q000150:complications / Q000473:pathology / Q000628:therapy*; D006801:Humans; D006969:Hypersensitivity, Immediate; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012128:Respiratory Distress Syndrome / Q000209:etiology; D012189:Retrospective Studies; D014182:Transplantation, Autologous