Definitions
Clinical: Kasabach-Merritt phenomenon (KMP) was defined strictly as severe thrombocytopenia with a platelet count ≤ 50,000/uL at diagnosis or prior to systemic medical therapy. Coagulopathy was defined less strictly and could include hypofibrinogenemia with a fibrinogen < 150mg/dL and/or D-dimer > 2 times the upper limit of normal at diagnosis or prior to systemic medical therapy.
Therapy: Treatment groups included: sirolimus (Siro), vincristine (VCR), Siro and VCR together (Siro+VCR), steroids only, and a minimal treatment group that received either beta-blocker, aspirin, or no medical therapy. Treatment groups were determined by the primary agent started within the first 30 days following treatment initiation. Patients in the Siro, VCR, or Siro+VCR categories were allowed to have also received steroids, but the primary drug therapy must have been initiated less than 30 days after steroids. Patients in the Steroid treatment group did not receive additional therapies. Patients in the Siro+VCR group received both drugs up-front within the 30 days. Patients included in the surgery/interventional radiology (IR) group had either surgical resection or IR embolization as their initial primary mode of treatment, even if they received medical therapy later in their course.
Response: Time to response was determined by number of days since first systemic therapy was initiated. For patients who received no systemic medical therapy, time to response was determined as the time from diagnosis or surgical intervention. Responses were categorized as subjective clinical response (ClinR), radiologic response (RadR), and hematologic response (HemR; in patients with KMP only). ClinR was defined as resolution of symptoms related to tumor, functional deficit, or decrease in size of tumor by visual inspection, even if not a complete response. RadR was defined as any measurable decrease in tumor size on radiographic imaging. If tumor measurements were available, the RECIST criteria for partial response could be used30. HemR in patients with KMP was defined as a platelet count > 100,000/μl x 2 consecutive lab measurements without transfusion. Durability of response was determined as time from first response to recurrent disease. Time from diagnosis and treatment initiation to persistent disease or progressive disease were also measured. Progressive disease was defined as any clinically significant increase in volume of tumor by history, exam, or radiologic imaging, worsening or persistence of KMP, or clinically significant worsening of pain or functional status as determined by treatment team. Investigators reported their criteria in determining recurrent, persistent, or progressive disease when applicable.