Showing papers by "Keith M. Sullivan published in 2000"

New Malignant Diseases After Allogeneic Marrow Transplantation for Childhood Acute Leukemia

Abstract: PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P < .001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed inc...

Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities

Abstract: This retrospective study describes the outcome in 53 patients who had immunosuppressive treatment changed from cyclosporine (CSP) to tacrolimus for resistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CSP-associated neurotoxicity (n = 17). Tacrolimus was administered at doses of 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, as tolerated. Median time of conversion to tacrolimus after transplant was day 47. Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades III or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution of GVHD after changing treatment to tacrolimus, with 18 showing no improvement. Eleven evaluable patients had therapy changed to tacrolimus for CSP-associated neurotoxicity at a median of 36 days after transplant. Eight patients had resolution of neurotoxicity and three had partial improvement. Eleven evaluable patients had therapy changed to tacrolimus for HUS at a median of 46 days after transplant. One patient had complete resolution of HUS and 10 showed no response. Side-effects related to tacrolimus included renal toxicity (34%), neurotoxicity (15%) and HUS (9%). Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CSP-associated neurotoxicity. While often successful for dealing with neurotoxicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD.

Bone Marrow Transplantation for Non-Malignant Disease

Abstract: This article reviews the experience in hematopoietic stem cell transplantation (HSCT) for non-malignant disease. HSCT has long been applied as treatment of life-threatening congenital immunodeficiency and metabolic diseases. In Section I, Dr. Parkman reviews that experience for severe combined immunodeficiency, Wiscott-Aldrich syndrome, hyper IGM syndrome, Chediak-Higashi disease and hereditary lymphohistiocytosis. The value of HSCT in genetic metabolic diseases such as osteopetrosis, osteogenesis imperfecta and the storage diseases are reviewed. In Section II, Dr. Walters reviews the experience over the last decade with allogeneic stem cell transplantation in patients with thalassemia major and sickle cell disease. In Section III, Dr. Sullivan reviews the more recent investigations using stem cell transplantation in patients with advanced autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis and juvenile rheumatoid arthritis. The pathogenesis and outcome with conventional care of these patients, the selection criteria and current results for HSCT, and the future directions in clinical research and patient care using this modality are addressed.

Impact of a Randomized, Controlled Trial of Liberal vs Conservative Hospital Discharge Criteria on Energy, Protein, and Fluid Intake in Patients Who Received Marrow Transplants

Abstract: Object To determine if adult patients who received marrow transplants had faster resumption of oral energy and nutrient intake and shorter duration of intravenous (IV) fluid requirement if discharged from the hospital earlier than is customary Design Randomized, controlled trial of patients remaining hospitalized because of inadequate oral intake Consenting patients were assigned randomly to remain hospitalized (hospital group) or be discharged to an ambulatory setting (ambulatory group) Subjects Seventy-eight patients of the Fred Hutchinson Cancer Research Center who were consuming less than 33% of estimated energy requirement and requiring up to 3,000mL of fluids per day intravenously Intervention Participants received nutrition counseling by a registered dietitian to promote resumption of oral intake Daily oral intake records were analyzed to determine energy and nutrient content Main outcome measures Days after study enrollment to consume 33% of energy and protein requirements and total number of days of IV fluid support were analyzed by group until discharge from the center, approximately 100 days after transplantation Statistical analyses Demographic data were defined by group means Differences between treatment procedures were determined by Cox regression analysis No variables were confounding Results The hospital group took fewer days than the ambulatory group to resume oral energy intake (45 vs 80, P =004) and to discontinue IV fluids (305 vs 485, P =019) There was no difference between groups in days of parenteral nutrition support ( P =817) or days to resume oral protein intake ( P =470) Applications/conclusions Oral and gastrointestinal complications delay resumption of oral energy and protein intakes after transplantation Earlier hospital discharge can achieve cost savings but may delay resumption of oral energy intake Because of continued high-risk nutrition status and potential for rapid change in medical status, nutrition assessment and counseling are necessary in both the hospital and ambulatory setting to promote resumption of oral intake and discontinuation of IV fluids J Am Diet Assoc 2000;100:1015–1022

New M alignant D iseases A fter A llogeneic M arrow Transplantation f or C hildhood A cute L eukemia

Abstract: Purpose: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. Patients and Methods: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an ageand sex-matched general population. Risks factors were evaluated using Poisson regression. Results: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P < .001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n 5 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] 5 3.1) and younger age at transplantation (RR 5 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR 5 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR 5 6.5), unrelated or HLA-disparate related donor (RR 5 7.5), T-cell‐depleted graft (RR 5 4.8), and antithymocyte globulin therapy (RR 5 3.1). Conclusion: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers. J Clin Oncol 18:348-357. © 2000 by American Society of Clinical Oncology.