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Biomedical subjects

George R Buchanan

Publications and source records attributed to George R Buchanan.

At least 19 recordsLinked to original sources

Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective study of 134 children from the Intercontinental Childhood ITP Study Group.

BACKGROUND: Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. PROCEDURE: Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in 25 countries participated in a splenectomy registry. Data from 153 patients were submitted, of whom 134 had a splenectomy and were analyzed. RESULTS: The median age at splenectomy was 11.8 (2.7-20.7) years. The median postsplenectomy follow-up was 2.0 (0.1-4.5) years. Pre-splenectomy vaccination was not administered in 21 children (15.7%). Open and laparoscopic splenectomy procedures were performed in 67 and 65 evaluable children, respectively. Surgical technique was not reported in two children. Overall immediate platelet response to splenectomy was achieved in 113 patients (86.3%). Eighty percent of responders maintained their status of response during the following 4 years. Older age, longer duration of ITP, and male gender correlated with a complete response. Post-splenectomy sepsis was reported in seven patients without lethal outcome, although sepsis might be differently defined at participating institutions. CONCLUSIONS: Splenectomy is effective in children with ITP. Management varies greatly in different institutions. These Registry data may serve as a basis for future clinical trials to assess the indication and timing of splenectomy.

Adolescent↗

Current challenges in the management of children with idiopathic thrombocytopenic purpura.

Much progress has been made during the past several decades in the diagnosis and management of childhood idiopathic thrombocytopenic purpura (ITP). Although we do not yet know ITP's cause, opportunities for research discovery in other areas have blossomed in recent years. One major step forward has been realization that outcomes other than platelet count are important in children with ITP, most especially the severity of hemorrhage, cost and side effects of treatment, and overall quality of life. The classical definition of chronic ITP (thrombocytopenia lasting greater than 6 months) has been questioned. Debate continues whether ITP can truly be cured, especially when it lasts for years. Much excitement has recently been generated as a result of a new mechanism of ITP treatment, that is, enhancing platelet production. Yet problems continue regarding how best to conduct research involving newly diagnosed ITP patients, for a number of barriers are still to be overcome. Fortunately, however, abundant information and support for ITP patients and their families is now much more available than in years past.

Child↗

Catheter-related deep venous thrombosis and other catheter complications in children with cancer.

PURPOSE: Asymptomatic deep vein thrombosis (DVT) is a complication of central venous catheter (CVC) use in children with cancer, but its clinical significance is not well defined. Children with CVCs commonly experience two other CVC-related complications: occlusion and infection. The aim of this study was to determine the frequency of these two complications and their association with DVT. PATIENTS AND METHODS: We conducted a retrospective cohort study of patients who were diagnosed with cancer. Data collected included number and type of catheter insertions, duration of use, reason for removal, associated catheter complications, and demographic information. RESULTS: Catheters were placed in 287 patients for a total of 128,403 days (mean, 290 +/- 269 days/catheter). Of 21 patients (7%) diagnosed with CVC-related DVT, only five had specific signs or symptoms. Nineteen (90%) of these 21 children had prior history of catheter occlusion, and 10 of the 19 also experienced infection. Ten children (48%) were not identified as having DVT until they had had multiple catheters with recurrent complications. Odds of having DVT were higher in patients who had a single catheter complicated by repeated occlusions (odds ratio [OR], 3.7; P = .001) or infection (OR, 2.2; P = .016). Patients experiencing both infection and occlusion were at 6.4 times (P < .0001) higher risk of developing DVT. CONCLUSION: Children with CVC-related DVT frequently have recurrent catheter complications. Unrecognized thrombosis may therefore be clinically important. Prospective studies are needed to determine if identification and treatment of occult DVT will prevent additional CVC-related complications and prolong the duration of catheter use.

Catheterization↗

Prognostic significance of early vaso-occlusive complications in children with sickle cell anemia.

Sickle cell anemia (SS) is highly phenotypically variable, and early predictors of outcome could guide clinical care. To determine whether early vaso-occlusive complications predicted subsequent adverse outcomes in the Dallas Newborn Cohort, we studied all members with SS or sickle-beta0-thalassemia who presented in their first year of life and had 5 years or more of follow-up. We defined 3 potential early predictors: hospitalizations in the first 3 years of life for (1) painful events other than dactylitis, (2) dactylitis, and (3) acute chest syndrome (ACS). We studied the associations of these predictors with the following late adverse outcomes (occurring after the third birthday): death, first overt stroke, use of disease-modifying therapy, and hospitalizations for pain events and ACS. None of the early events predicted death or stroke. Early pain and ACS both predicted a modest, temporary increase in the number of later painful episodes, but early ACS strongly increased the odds of more frequent ACS throughout childhood. Dactylitis had limited utility as a predictor. Although we still lack a useful prognostic framework for young children with SS, those who experience early ACS might be candidates for higher risk interventions to mitigate or cure their disease.

Acute Disease↗

Incidence and clinical relevance of abnormal complete blood counts in long-term survivors of childhood cancer.

BACKGROUND: The purpose of the study was to determine the incidence and clinical significance of abnormal complete blood counts (CBCs) obtained during follow-up of childhood cancer survivors. METHODS: A retrospective cohort study was conducted on 193 survivors, diagnosed between 1970-1986, who were followed in our center's After Cancer Experience Program and are participants in the Childhood Cancer Survivor Study. Of these patients, 49% were female and 25% were racial/ethnic minorities. The primary outcome was determination of the cumulative percentage of patients having an abnormal CBC by 2 or 3 standard deviations (SDs). Four components of the CBC were examined and employed to define an abnormal CBC: low white blood cell count (WBC), high mean corpuscular volume (MCV), low platelet count, and low hemoglobin concentration. Association of treatment exposures to abnormal values was assessed with a multilevel logistic model. RESULTS: There were 1297 patient visits during 1401 person-years of follow-up. The mean number of visits per survivor was 6.7 (SD 4.2). The cumulative percentage of subjects with at least one abnormal CBC was 70%. The cumulative percent of subjects with a value abnormal by 2 SD was WBC = 23%, MCV = 37%, platelets = 9%, hemoglobin = 49%. For values abnormal by 3 SD, the frequencies were WBC = 3%, MCV = 20%, platelets = 1%, hemoglobin = 27%. None of the patients developed myelodysplastic syndrome or a secondary leukemia during the follow-up period. Exposure to epipodophyllotoxins was associated with an increased risk of having abnormally high MCV values. CONCLUSIONS: Mildly abnormal CBC values are common in survivors of childhood cancer. Abnormal values are often of questionable significance but seem to persist over time. Epipodophyllotoxin therapy was found to be associated with increased frequency of high MCV levels.

Adolescent↗

Post-thrombotic syndrome is uncommon in childhood cancer survivors.

Deep vein thrombosis occurs in up to 50% of children with tunneled central venous catheters (CVCs). CVC-related deep vein thrombosis involving the upper extremity is usually asymptomatic but can result in post-thrombotic syndrome (swelling, pain, skin changes, and functional impairment). In a cohort of childhood cancer survivors evaluated clinically a mean of 7.5 +/- 2.8 years after completion of therapy who previously had CVCs in place for a median 15.5 months, none of 50 patients (95% CI = 0% to 6%) had these features diagnostic of post-thrombotic syndrome. Five patients had arm circumference 3% to 5% greater ipsilateral to the prior CVC.

Adolescent↗

Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia.

A retrospective cohort study of children with sickle cell anemia (SCA) and strokes was used to test the hypothesis that exchange transfusion at the time of stroke presentation more effectively prevents second strokes than does simple transfusion. Children receiving simple transfusion had a 5-fold greater relative risk (95% confidence interval = 1.3 to 18.6) of second stroke than those receiving exchange transfusion.

Adolescent↗

Venous thrombosis and thromboembolism in children with osteomyelitis.

OBJECTIVE: To determine the prevalence and clinical features of deep vein thrombosis (DVT) complicating osteomyelitis during childhood. STUDY DESIGN: We retrospectively reviewed medical records of all patients with osteomyelitis admitted to Children's Medical Center Dallas between July 1, 2003 and December 31, 2004. Analysis was performed on patients with proximal upper or lower extremity, pelvic or vertebral osteomyelitis (a subgroup considered to be at highest risk for infection-related thrombosis). RESULTS: Thirty-five patients had confirmed osteomyelitis of the proximal humerus, proximal tibia/fibula, femur, pelvis, or vertebrae. Ten of these 35 children (29%) developed DVT during the acute infection based on imaging studies performed. Eight thrombi occurred adjacent to the infection and two occurred in relation to central venous catheters. Six of the 10 children with DVT also had evidence of infection disseminated to lung, brain, or heart, compared with only 1 of 25 patients without DVT (P = .001). Hospitalization was longer in those with DVT than without (33.5 v. 14.2 days, P = .001). CONCLUSION: Thromboembolic complications can occur in the setting of osteomyelitis, and affected patients may be at higher risk of disseminated infection.

Acute Disease↗

Hematopoietic stem cell transplantation after first marrow relapse of non-T, non-B acute lymphoblastic leukemia: a pediatric oncology group pilot feasibility study.

BACKGROUND: Relapsed acute lymphoblastic leukemia (ALL) in children is associated with a poor outcome, especially for those patients whose relapse occurs during the first 36 months after diagnosis. The best therapy for these patients is not known. This study was designed to evaluate the feasibility of enrolling children with recurrent ALL in a standardized treatment protocol that included receipt of a hematopoietic stem cell transplant (HSCT). PROCEDURE: Eligible patients with a bone marrow relapse of non-T, non-B ALL underwent a common induction and consolidation followed by receipt of either an allogeneic HSCT from a human leukocyte antigen (HLA)-identical sibling or an autologous HSCT purged with B-4 blocked ricin. A common conditioning regimen was used for all patients. RESULTS: Twenty-eight patients from eight institutions were enrolled. Fourteen patients did not receive a transplant during the study, because of toxicity (4), relapse (1), inadequate purging (1), and parental or physician preference for an alternative donor transplant (8). Six patients received allogeneic HSCTs. Five of them have remained in remission for a median of 78 months. Eight patients received autologous HSCTs purged with B4-blocked ricin. Four have remained in remission for a median of 94 months. Of the nine patients who received alternative donor transplants, only two remain in remission. CONCLUSION: We conclude that well designed and controlled prospective studies are necessary to define the role of HSCTs in children with recurrent ALL. In order to be successful, such studies must have the full support of participating centers. Autologous HSC transplantation may have a role in the treatment of relapsed ALL, but further studies are needed.

Adolescent↗

Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura.

We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 x 10(9)/L (50,000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.

Adolescent↗

Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without pre-operative blood transfusion.

BACKGROUND: Pre-operative red blood cell (RBC) transfusions are often recommended for patients with sickle cell disease (SCD) who require elective surgery under general anesthesia. However, definitive randomized studies demonstrating the benefit of transfusions in this setting have not been conducted. In particular, the merits of transfusion prior to minor or low-risk surgical procedures in children with SCD have not been demonstrated. PROCEDURE: We hypothesized that children with sickle cell anemia (Hb SS) who have minor elective surgical procedures develop few complications even without pre-operative transfusion. We accessed our Comprehensive Sickle Cell Program's Database to identify all such procedures performed during a 13-year period. Medical records were reviewed to characterize the surgical procedure, the use of transfusions, and perioperative complications. RESULTS: Twenty-eight children with Hb SS had a total of 38 minor surgical procedures. No perioperative transfusions were given in 34 of the cases (85%). Five of these 34 surgeries (15%) were associated with minor post-operative complications (fever or transient pain). No post-operative acute chest syndrome was encountered. CONCLUSIONS: Minor or low-risk elective surgical procedures in children with Hb SS may not routinely require pre-operative transfusion. A randomized clinical trial to compare transfusion with no transfusion for minor surgical procedures is needed.

Adolescent↗

Prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor decrease febrile neutropenia after chemotherapy in children with cancer: a meta-analysis of randomized controlled trials.

PURPOSE: To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality. METHODS: We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical. From 971 reviewed study articles, 16 were included. RESULTS: The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%). Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P =.01), and a decrease in hospitalization length, with a weighted mean difference of -1.9 days (95% CI, -2.7 to -1.1 days; P <.00001). CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P =.02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P =.02). There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, -4.3; 95% CI, -10.6 to 2.0 days; P =.2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P =.97). CONCLUSION: CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.

Adolescent↗

Survival of children with sickle cell disease.

Contemporary survival data are not available for children with sickle cell disease (SCD). The few previous childhood SCD cohort studies do not reflect the benefits of modern therapy. We defined an inception cohort of newborns with sickle cell anemia (SS), sickle-beta degrees -thalassemia (S beta degrees ), sickle-hemoglobin C disease (SC), or sickle-beta(+)-thalassemia (Sbeta(+)) who were identified by newborn screening and followed for up to 18 years. The incidence of death and stroke were calculated. Overall survival, SCD-related survival (considering only SCD-related deaths), and strokefree survival were determined. The 711 subjects provided 5648 patient-years of observation. Twenty-five subjects died; mean age at death was 5.6 years. Five patients died from infection. Thirty had at least one stroke. Among SS and Sbeta degrees subjects (n = 448), the overall rates of death and stroke were 0.59 and 0.85/100 patient-years. Survival analysis of SS and Sbeta degrees subjects predicted the cumulative overall, SCD-related, and stroke-free survival to be 85.6%, 93.6%, and 88.5% by 18 years of age. No SCD-related deaths or strokes occurred in SC or Sbeta(+) subjects (n = 263). Childhood mortality from SCD is decreasing, the mean age at death is increasing, and a smaller proportion of deaths are from infection.

Adolescent↗