Agrylin

Clinical Pharmacology

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Clinical Pharmacology

Agrylin

CML

Persistent granulocyte count ≥ 50,000/µL without evidence of infection
Absolute basophil count ≥ 100/µL
Evidence for hyperplasia of the granulocytic line in the bone marrow
Philadelphia chromosome is present
Leukocyte alkaline phosphatase ≤ lower limit of the laboratory normal range

PV^†

A1 Increased red cell mass
A2 Normal arterial oxygen saturation
A3 Splenomegaly
B1 Platelet count ≥ 400,000/µL, in absence of iron deficiency or bleeding
B2 Leukocytosis ( ≥ 12,000/µL, in the absence of infection)
B3 Elevated leukocyte alkaline phosphatase
B4 Elevated serum B12

^†Diagnosis positive if A1, A2, and A3 present; or, if no splenomegaly, diagnosis is positive if A1 and A2 are present with any two of B1, B2, or B3.

MMM

Myelofibrotic (hypocellular, fibrotic) bone marrow
Prominent megakaryocytic metaplasia in bone marrow
Splenomegaly
Moderate to severe normo-chromic normocytic anemia
White cell count may be variable; (80,000-100,000/µL)
Increased platelet count
Variable red cell mass; teardrop poikilocytes
Normal to high leukocyte alkaline phosphatase
Absence of Philadelphia chromosome

Patients were enrolled in clinical trials if their platelet count was ≥ 900,000/µL on two occasions or ≥ 650,000/µL on two occasions with documentation of symptoms associated with thrombocythemia. The mean duration of anagrelide therapy for ET, PV, CML, and OMPD patients was 65, 67, 40, and 44 weeks, respectively; 23% of patients received treatment for 2 years. Patients were treated with anagrelide starting at doses of 0.5-2.0 mg every 6 hours. The dose was increased if the platelet count was still high, but to no more than 12 mg each day. Efficacy was defined as reduction of platelet count to or near physiologic levels (150,000-400,000/µL). The criteria for defining subjects as "responders" were reduction in platelets for at least 4 weeks to ≤ 600,000/µL, or by at least 50% from baseline value. Subjects treated for less than 4 weeks were not considered evaluable. The results are depicted graphically below:

Patients with Thrombocytosis Secondary to Myeloproliferative Disorders: Mean Platelet Count During Anagrelide Therapy

	Time onTreatment
		Weeks				Years
	Baseline	4	12	24	48	2	3	4
Mean*	1131	683	575	526	484	460	437	457
N	923^†	868	814	662	530	407	207	55
*x 10³/µL ^† Nine hundred and forty-two subjects with myeloproliferative disorders were enrolled in three research studies. Of these, 923 had platelet counts over the duration of the studies.