No abstract

Venous malformations are slow-flow congenital vascular malformations that enlarge as the child ages and may be associated with localised intravascular coagulation, a consumptive coagulopathy characterised by elevated D-dimer and decreased fibrinogen levels. The authors review the known correlations between localised intravascular coagulation and venous malformation number, size and planes involved, and call attention to the concept of the progression of localised intravascular coagulopathy as the child ages and their venous malformations enlarge. The authors also discuss the identified therapeutic options for its investigation, management and treatment, including compression garments, anti-coagulation therapy, sclerotherapy, endovascular laser, surgical excision and sirolimus (rapamycin). Evidence for protocol improvements that may be instigated for the optimal physical and medical therapy of venous malformations complicated by localised intravascular coagulopathy is reviewed.

BackgroundOver the last 25 years, donor source, conditioning, graft-versus-host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high-risk patients in first and subsequent remission. There is a large burden of infectious and pre-HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased.ProcedureA retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8-year periods (Period 1: 1/1/1984–31/8/1992, Period 2: 1/9/1992–30/4/2001, Period 3: 1/5/2001–31/12/2009).ResultsDespite a significant increase in unrelated donor HSCT, event-free and OS over 25 years improved significantly. (EFS 31.6–64.8%, P = 0.0027; OS 41.8–78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time.ConclusionEFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post-HSCT are unchanged, and remain the focus for improvement.

Pregnancy and delivery are critical times for women with bleeding disorders, with mothers, and possibly their affected infants, being exposed to a variety of haemostatic challenges. Management of women with bleeding disorders during pregnancy involves a multidisciplinary team including, but not limited to, an obstetrician, an anaesthetist and a haematologist. This consensus document from the Australian Haemophilia Centre Directors’ Organisation (AHCDO) provides practical information for clinicians managing women with bleeding disorders during pregnancy. Included are: the expected physiological response in pregnancy in such women; management of pregnancy, labour and delivery, as well as obstetric anaesthesia issues, postpartum care, and reducing and treating postpartum haemorrhage; and management of infants at risk of a bleeding disorder and of bleeding in neonates. The guidelines were developed after extensive consultation, face‐to‐face meetings and revisions. The final document represents a consensus opinion of all AHCDO members. Where evidence is lacking, recommendations are based on clinical experience and consensus opinion.

Factor replacement with BIOSTATE(®), a factor VIII (FVIII)/von Willebrand factor concentrate, forms the mainstay of treatment for children with von Willebrand disorder (VWD) in Australia and New Zealand. However, published data on the clinical efficacy and safety of BIOSTATE in the VWD paediatric population are limited. We retrospectively assessed the efficacy and safety of BIOSTATE in 43 children with VWD who received treatment for surgery, non-surgical bleeds or continuous prophylaxis at eight paediatric haemophilia centres in Australia and New Zealand. Data were collected on patient demographics, disease history, treatment history, dosage, administration, adverse reactions, concomitant medications and excessive bleeding events. BIOSTATE provided excellent/good haemostatic efficacy in 90% of surgical procedures (n = 42) with a mean daily FVIII dose of 47 IU FVIII:C kg(-1) and a median treatment duration of 3 days. Excellent/good haemostatic efficacy was achieved in 94% of non-surgical bleeding events (n = 72) with a mean FVIII dose of 45 IU FVIII:C kg(-1) day(-1) and a median treatment duration of 1 day. There were no bleeding events attributable to lack of efficacy. One case of nausea, possibly related to BIOSTATE administration, was reported. These results suggest that BIOSTATE is safe and effective for the treatment and prophylaxis of bleeding in children with VWD.

Younger patients are at increased risk of osteochondroma following TBI. Review of the available literature suggests a low malignant potential of radiation-induced osteochondromas. Knowledge about the behaviour of post-irradiation osteochondromas will help clinicians manage patients appropriately.

Background:All established disease-modifying drugs for multiple sclerosis require parenteral administration, which can cause difficulties for some patients, sometimes leading to suboptimal adherence. A new electronic autoinjection device has been designed to address these issues.Methods:Patients with relapsing multiple sclerosis currently receiving subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, or glatiramer acetate completed an online questionnaire (July 4–25, 2008) that surveyed current injection practices, experiences with current injection methods, and impressions and appeal of the new device.Results:In total, 422 patients completed the survey, of whom 44% used autoinjectors, 43% prefilled syringes, and 13% syringes and vials; overall, 66% currently self-injected. Physical and psychological barriers to self-injection included difficulty with injections, needle phobia, and concerns over correct injection technique. Only 40% of respondents were “very satisfied” with their current injection method. The new electronic autoinjector was rated as “very appealing” by 65% of patients. The benefits of the new device included the ability to customize injection settings and to review dosing history.Conclusion:New technologies may help patients overcome physical and psychological barriers to self-injection. The combination of a reliable and flexible autoinjection device with dose-monitoring technology may improve communication between health care professionals and patients, and improve treatment adherence.

Background. In human brain tumors, sensitivity to procarbazine as measured by sensitivity in a xenograft tumor model correlated inversely with amounts of the DNA repair enzyme O6‐alkylguanine DNA alkyltransferase(AT). Methods. To test the hypothesis that mutations of the p53 tumor suppressor gene in human tumors also can correlate with the response to chemotherapy, p53 mutations were identified in primary human malignant brain tumors and cell lines in which AT activity and procarbazine sensitivity in a xenograft model was ascertained. Results. Mutations were identified in 7 of 21 (33%) specimens tested. Specimens containing p53 mutations tended to exhibit an increased growth delay in procarbazine‐treated xenografts and lower amounts of AT. Conclusions. p53 mutations in brain tumors may contribute to procarbazine sensitivity by failing to induce arrest at the G1/S cell‐cycle checkpoint, thereby preventing the repair of procarbazine‐induced genetic alterations. Cancer 1995;75:1339‐42.