Objective To examine the presentation characteristics of patients with kaposiform hemangioendothelioma (KHE) to describe the spectrum of disease and risk factors for Kasabach-Merritt phenomenon (KMP). Study design Retrospective review of 163 patients referred to the Vascular Anomalies Center at Children’s Hospital Boston for KHE between 1991 and 2009 identified 107 patients with sufficient data for inclusion. Results The prevalence of KHE in Massachusetts is approximately 0.91/100,000 children. KHE manifested in infancy in 93% of cases; 60% as neonates. Common presenting features included enlarging cutaneous lesion (75%), thrombocytopenia (56%), and musculoskeletal pain or decreased function (23%). Cutaneous KHE favored the extremities, especially overlying joints. In our cohort 71% developed KMP (11% after initial presentation), and 11% of patients lacked cutaneous findings. Retroperitoneal and intrathoracic lesions, though less common, were complicated by KMP in 85% and 100% of cases, respectively. Compared with superficial lesions, KHE infiltrating into muscle or deeper was 6.3 fold more likely to manifest KMP, and 18-fold higher if retroperitoneal or intrathoracic. KHE limited to bone or presenting after infancy did not manifest KMP. Conclusion An enlarging lesion is the most common presenting feature of KHE in infancy. Older patients with KHE or those lacking cutaneous manifestations present with musculoskeletal complaints or atypical symptoms. The risk of KMP increases dramatically when tumor infiltrates muscle or when KHE arises in the retroperitoneum or mediastinum.

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

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Background Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein, progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. Methods Thirty-seven participants with HGPS received pravastatin, zoledronic acid and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. Results No participants withdrew due to side effects. Primary outcome success was pre-defined by improved per patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were pre-defined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001–0.006) bone mineral density, and 1.5–1.8-fold radial bone structure increases (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0 to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. Conclusions Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit, but likely no added cardiovascular benefit with addition of pravastatin and zoledronic acid. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.