Vilmarie Rodriguez

Successful treatment of refractory myasthenia gravis using rituximab: a pediatric case report

We report the successful use of anti-CD20 therapy in a child with refractory myasthenia gravis (MG), an antibody-mediated autoimmune disease, who did not respond to conventional therapy. After initiation of anti-CD20 therapy, clinical improvement (muscular strength, pulmonary function) was observed.

Twenty years of follow-up among survivors of childhood and young adult acute myeloid leukemia: A report from the Childhood Cancer Survivor Study

Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML).

Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 ± 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d × 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

The Ped-APS Registry: the antiphospholipid syndrome in childhood

In recent years, antiphospholipid syndrome (APS) has been increasingly recognised in various paediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way. The project of an international registry of paediatric patients with APS (the Ped-APS Registry) was initiated in 2004 to foster and conduct multicentre, controlled studies with large number of paediatric APS patients. The Ped-APS Registry is organised as a collaborative project of the European Forum on Antiphospholipid Antibodies and Juvenile Systemic Lupus Erythematosus Working Group of the Paediatric Rheumatology European Society. Currently, it documents a standardised clinical, laboratory and therapeutic data of 133 children with antiphospholipid antibodies (aPL)-related thrombosis from 14 countries. The priority projects for future research of the Ped-APS Registry include prospective enrolment of new patients with aPL-related thrombosis, assessment of differences between the paediatric and adult APS, evaluation of proinflammatory genotype as a risk factor for APS manifestations in childhood and evaluation of patients with isolated nonthrombotic aPL-related manifestations.

Comparison of coagulation factor XIII content and concentration in cryoprecipitate and fresh-frozen plasma.

BACKGROUND: For patients with plasma coagulation factor XIII (pFXIII) deficiency, recommended means of replacement include infusions of fresh‐frozen plasma (FFP), cryoprecipitate, or (where available) factor (F)XIII concentrates. Quantitative differences in pFXIII concentration in FFP and cryoprecipitate are not well defined and were, therefore, the subject of this study.

Rituximab for successful management of probable pediatric catastrophic antiphospholipid syndrome

Catastrophic antiphospholipid syndrome (CAPS) is a life‐threatening condition characterized by small‐vessel thrombi and a rapid onset of multiorgan system failure associated with systemic inflammatory response syndrome. Current treatment options include anticoagulants, corticosteroids, plasma exchange, and intravenous immunoglobulin, but these are not always effective. Rituximab, a chimeric anti‐CD20 monoclonal antibody, may help eliminate autoreactive B cells and thus limit the rapid inflammatory process involved in CAPS. We describe the use of rituximab in the successful initial management of a probable case of pediatric CAPS. Pediatr Blood Cancer 2009;52:536–538.

Use of infliximab-daclizumab combination for the treatment of acute and chronic graft-versus-host disease of the liver and gut

Infliximab‐daclizumab was used to treat acute and chronic liver and gut graft‐versus‐host disease (GVHD) in two children after standard immunosuppressive therapy failed. Infliximab (10 mg/kg weekly, 4 doses) and daclizumab (1 mg/kg, days 1, 4, 8, 15, and 22) were given over 1 month. In case 1, grade 2 chronic GVHD of the liver developed 1 year after transplantation and failed to improve with tacrolimus, mycophenolate mofetil, and prednisone. In case 2, corticosteroid‐unresponsive grade 3 acute liver and gut GVHD developed on day +37. In both patients, GVHD responded to the infliximab‐daclizumab regimen without toxicity and immunosuppressive therapy was discontinued. Pediatr Blood Cancer 2007;49:212–215.

To circumcise or not to circumcise? Circumcision in patients with bleeding disorders.

Summary.  Circumcision is one of the most common procedures performed in male neonates, but few published reports have described circumcision in patients with bleeding disorders. The aim of this study was to analyse outcomes of circumcision among children evaluated at our institution to determine the extent of complications and to provide guidelines for circumcision management. We searched our patient database for records of children who were followed up at the Mayo Clinic Comprehensive Hemophilia Center from 2000 through 2007 and who had been circumcised. We retrospectively reviewed the medical records to document complications and determine management strategies in this patient population. Of 55 children and young adults identified (median [range] age, 15 years [11 months to 21 years]), 48 patients were circumcised. Indications for circumcision were parental request (n = 45) and medical recommendation (n = 3). Twelve of 21 patients with a known bleeding disorder at the time of circumcision received factor replacement before the procedure. Three of these 21 patients had bleeding complications. Of the other 27 patients, who were diagnosed later in life as having a bleeding disorder, 8 had bleeding complications. The overall incidence of bleeding after circumcision was 23% (11/48). The 23% overall incidence of bleeding complications in our patients with bleeding disorders is comparable to that reported for patients without a bleeding disorder (0.1–35%). Some of our patients had significant bleeding despite adequate factor replacement before and after the procedure. Parents and patients must be aware that bleeding risk is a possibility despite adequate factor replacement for hemostasis.

Central venous access devices for paediatric patients with haemophilia: a single‐institution experience

Summary.  Use of a central venous access device (CVAD) can facilitate early introduction of home‐based infusion of factor concentrate for long‐term prophylaxis or immune tolerance therapy in children with bleeding disorders. The aim was to review outcomes associated with use of CVAD. Retrospective review of paediatric patients with bleeding disorders was observed at the Mayo Clinic Comprehensive Hemophilia Center. Thirty‐seven CVAD were placed in 18 patients (haemophilia A [n = 15], type 3 von Willebrand disease [n = 2] and haemophilia B [n = 1]). Follow‐up was for 45 952 CVAD days, and median time that CVAD remained in place was 1361 days per device. Factor VIII (FVIII) inhibitors were present in 4 of the 15 patients. Ten CVAD‐related infections occurred (median, 672 days; range, 72–1941 days), of which six were in one patient with FVIII inhibitors. Overall infection rate was 0.22 (95% confidence interval [CI], 0.10–0.40) per 1000 CVAD days, with 0.11 infections in patients without FVIII inhibitors compared with a pooled incidence of 0.66 (95% CI, 0.44–0.97) reported in the literature. Indications for removal of 27 CVAD were blockage, change to peripheral venous access, catheter displacement, infection, leak in the port septum, short catheter and skin erosion. No clinically apparent thrombosis or sequelae of thrombosis were observed. Infection is the most common complication associated with CVAD use and is increased in patients who have inhibitors. The low rate of clinically apparent thrombosis reflects our practice of not screening for thrombosis. The low infection rate reflects our practice of using and reinforcing the aseptic technique.

Health‐related quality of life in children and young adults with post‐thrombotic syndrome: Results from a cross‐sectional study

While post‐thrombotic syndrome (PTS) is increasingly recognized in children with a history of deep vein thrombosis (DVT), its impact on the health‐related quality of life (HRQoL) is unknown. Our objective was to evaluate the association between the PTS and HRQoL by surveying a cohort of patients treated at our institution for DVT.