Denise M. Adams

Sirolimus for the treatment of complicated vascular anomalies in children.

Vascular anomalies comprise a diverse group of diagnoses. While infantile hemangiomas are common, the majority of these conditions are quite rare and have not been widely studied. Some of these lesions, though benign, can impair vital structures, be deforming, or even become life‐threatening. Vascular tumors such as kaposiform hemangioendotheliomas (KHE) and complicated vascular malformations have proven particularly difficult to treat.

Kasabach-Merritt phenomenon : a retrospective study of treatment with vincristine

Purpose Kasabach-Merritt phenomenon (KMP) is characterized by profound thrombocytopenia, microangiopathic hemolytic anemia, a consumptive coagulopathy, and an enlarging vascular lesion. The syndrome develops in infancy and is associated with a high morbidity and mortality rate. The purpose of this study was to assess the effectiveness of vincristine in the treatment of KMP. Methods We retrospectively reviewed the clinical and laboratory data of 15 patients with KMP treated with vincristine at 9 institutions across the United States, South America, and Europe. Results All 15 patients had profound thrombocytopenia and consumption of fibrinogen at presentation. Ten patients had biopsies of their lesions, and results included five (33.3%) kaposiform hemangioendotheliomas, three (20%) tufted angiomas, one lesion (6.7%) with features of both kaposiform hemangioendothelioma and tufted angioma, and one (6.7%) unclassified vascular tumor. All 15 patients had an increase in platelet count of at least 20,000 with an average response time of 4.0 weeks after initiation of vincristine therapy. Thirteen patients had an increase in fibrinogen level of 50 mg/dL with an average response time of 3.4 weeks. In 13 patients there was a significant decrease in the size of the vascular lesion. The average duration of treatment was 21.5 (±12.6) weeks. Four patients (26%) relapsed. All four were successfully treated with a second course of vincristine. Complications included one patient with abdominal pain, one patient with transient loss of deep tendon reflexes, and one patient with irritability. Conclusion Vincristine presents a safe and sometimes effective treatment option in the management of KMP.

Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies.

BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m2 per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.

The Safety of Pediatric Acupuncture: A Systematic Review

CONTEXT: Acupuncture is increasingly used in children; however, the safety of pediatric acupuncture has yet to be reported from systematic review. OBJECTIVE: To identify adverse events (AEs) associated with needle acupuncture in children. METHODS: Eighteen databases were searched, from inception to September 2010, irrespective of language. Inclusion criteria were that the study (1) was original peer-reviewed research, (2) included children from birth to 17 years, inclusively, (3) involved needle acupuncture, and (4) included assessment of AEs in a child. Safety data were extracted from all included studies. RESULTS: Of 9537 references identified, 450 were assessed for inclusion. Twenty-eight reports were included, and searches of reference lists identified 9 additional reports (total: 37). A total of 279 AEs were identified, 146 from randomized controlled trials, 95 from cohort studies, and 38 from case reports/series. Of the AEs, 25 were serious (12 cases of thumb deformity, 5 infections, and 1 case each of cardiac rupture, pneumothorax, nerve impairment, subarachnoid hemorrhage, intestinal obstruction, hemoptysis, reversible coma, and overnight hospitalization), 1 was moderate (infection), and 253 were mild. The mild AEs included pain, bruising, bleeding, and worsening of symptoms. We calculated a mild AE incidence per patient of 168 in 1422 patients (11.8% [95% confidence interval: 10.1–13.5]). CONCLUSIONS: Of the AEs associated with pediatric needle acupuncture, a majority of them were mild in severity. Many of the serious AEs might have been caused by substandard practice. Our results support those from adult studies, which have found that acupuncture is safe when performed by appropriately trained practitioners.

Spectrum of hepatic hemangiomas: management and outcome.

PURPOSE Infants with multiple cutaneous hemangiomas often present with hepatic hemangiomas. They can follow a benign clinical course or require complex management. We reviewed our experience in the management of hepatic hemangiomas. METHODS We performed a retrospective review of patients (1996-2007) with hepatic hemangiomas treated in our institution. RESULTS Twenty-six patients were diagnosed with hepatic hemangiomas as follows: 8 focal, 12 multiple, and 6 diffuse lesions. Nineteen (73%) patients had associated cutaneous hemangiomas. Sixteen patients had multiple and 3 patients had single cutaneous hemangiomas. All patients with multiple or diffuse liver lesions were screened for heart failure and hypothyroidism. Congestive heart failure developed in 4 patients, 3/4 of these patients had diffuse lesions. Two patients required thyroid replacement because of elevated thyroid-stimulating hormone. Because of progression of disease, 9 patients required steroid treatment. Two patients were treated with vincristine and 3 patients received alpha-interferon because of poor response to steroid treatment. Two patients went on to surgical resection for failed response to medical management and worsening heart failure (left lobectomy, liver transplant). Both patients had uncomplicated postoperative courses. Five patients had a previously undescribed constellation of rapidly involuting cutaneous hemangiomas (gone by 3 months, glut-1-negative) with associated liver lesions also resolving at a faster pace (mean resolution of cutaneous hemangiomas, 1.9 vs 7.9 months; P = .001; liver, 5.8 vs 25.3 months; P = .004). All patients in our series survived. CONCLUSION Patients with multiple cutaneous hemangiomas should be screened for hepatic lesions. Patients with diffuse or multifocal liver hemangiomas should be screened for congestive heart failure and hypothyroidism. A subgroup of rapidly involuting cutaneous hemangiomas have a significantly shorter time for involution of hepatic lesions. The status of cutaneous lesions can be used as indicators for the liver hemangiomas.

Infantile hemangiomas with unusually prolonged growth phase: a case series.

BACKGROUND Most infantile hemangiomas (IHs) complete their proliferative growth phase before 9 months of age, but those with unusually prolonged growth create unique clinical challenges. We performed a retrospective case series of IHs with prolonged growth to further characterize these lesions and their treatment. OBSERVATIONS We identified 23 patients as having IHs with prolonged growth after 9 months of age, with growth to a mean age of 17 months. All of the IHs had a deep dermal to subcutaneous component, all had either segmental or indeterminate morphologic characteristics, and 39% involved the parotid gland. A total of 20 of 23 received prolonged treatment with systemic corticosteroids (mean duration of treatment, 11 months), and 9 of 20 received additional systemic therapies (vincristine sulfate and/or interferon alfa-2a or alfa-2b). CONCLUSIONS Prolonged growth was observed primarily in IHs with a deep component and segmental morphologic characteristics. Recognition of this subset of hemangiomas is important for clinicians, and further study of IHs may provide clues to their pathogenesis.

Erythrocytapheresis can reduce iron overload and prevent the need for chelation therapy in chronically transfused pediatric patients

Purpose This research was undertaken to determine the advantages, complications, costs, and efficacy of erythrocytapheresis in young pediatric patients who receive chronic erythrocyte transfusion therapy. Patients and Methods We retrospectively analyzed data for 10 children who received erythrocytapheresis for an average of 16 months. Erythrocytapheresis was compared to simple transfusion therapy with respect to annual blood unit exposure, occurrence of alloimmunization, and costs. Serum ferritin levels were compared before and after the period of erythrocytapheresis. Results Erythrocytapheresis was well tolerated, even in children as young as 5 years or as small as 20 kg. It required a greater annual unit exposure than simple transfusions, but did not increase alloimmunization. Ferritin levels decreased significantly in children receiving concurrent deferoxamine, and decreased or stablized in those not on chelation therapy. Children started on erythrocytapheresis soon after stroke have not developed iron overload. Although the costs of erythorocytapheresis exceed that of simple transfusion, the substantial costs of deferoxamine therapy should be considered; one child on erythrocytapheresis has been able to discontinue chelation therapy following normalization of his ferritin level. Conclusion Erythrocytapheresis is a safe and effective method for young patients receiving chronic erythrocyte transfusions. Erythrocytapheresis can reduce total iron burden and may obviate the need for expensive chelation therapy.

Prospective Study of Spinal Anomalies in Children with Infantile Hemangiomas of the Lumbosacral Skin

OBJECTIVE To prospectively evaluate a cohort of patients with infantile hemangioma in the midline lumbosacral region for spinal anomalies to determine the positive predictive value of infantile hemangioma for occult spinal anomalies and to make evidence-based recommendations for screening. STUDY DESIGN A multicenter prospective cohort study was performed at 9 Hemangioma Investigator Group sites. RESULTS Intraspinal abnormalities were detected in 21 of 41 study participants with a lumbosacral infantile hemangioma who underwent a magnetic resonance imaging evaluation. The relative risk for all patients with lumbosacral infantile hemangiomas for spinal anomalies was 640 (95% confidence interval [CI], 404-954), and the positive predictive value of infantile hemangioma for spinal dysraphism was 51.2%. Ulceration of the hemangioma was associated with a higher risk of having spinal anomalies. The presence of additional cutaneous anomalies also was associated with a higher likelihood of finding spinal anomalies; however, 35% of the infants with isolated lumbosacral infantile hemangiomas had spinal anomalies, with a relative risk of 438 (95% CI, 188-846). The sensitivity for ultrasound scanning to detect spinal anomalies in this high-risk group was poor at 50% (95% CI, 18.7%-81.3%), with a specificity rate of 77.8% (95% CI, 40%-97.2%). CONCLUSIONS Infants and children with midline lumbosacral infantile hemangiomas are at increased risk for spinal anomalies. Screening magnetic resonance imaging is recommended for children with these lesions.

Oral rapamycin in the treatment of patients with hamartoma syndromes and PTEN mutation

Bannayan–Riley–Ruvacalba syndrome (BRRS) belongs to the PTEN hamartoma tumor syndromes and is characterized by a high risk of malignancy in early adulthood added to local destructive effects of hamartomas in childhood. There is no standard treatment for this condition and patients are usually offered symptomatic surgical relief. Rapamycin has been reported to be effective in the management of other conditions associated with PTEN mutation. We report here a case of BRRS in a 6‐year‐old male with progressive loss of function of left hand and forearm associated with pain. He was treated with oral rapamycin and regained pain‐free full mobility. Pediatr Blood Cancer 2011; 57: 321–323.

High-dose oral dexamethasone therapy for chronic childhood idiopathic thrombocytopenic purpura

Because high-dose oral dexamethasone therapy has been reported to be effective for adults with idiopathic thrombocytopenic purpura, we assessed the short-term efficacy and toxicity of dexamethasone in seven children with chronic or refractory idiopathic thrombocytopenic purpura. Dexamethasone therapy was effective and well tolerated; further long-term studies are warranted.