Alemtuzumab Causes Significant, Transient, Post-Infusion Thrombocytopenia and Other Non-Autoimmune Cytopenias Following Initial and Subsequent Courses
Objectives: Report PI, transient cytopenias (thrombocytopenia [TP] and monocytopenia) associated with ALE.
Methods: Hemograms (CBC) from ALE-treated MS patients from phase I trial of ALE in MS. 1 to 7 courses of CBC data were reviewed. An immediate PI CBC, at end of last infusion in each course, was collected. TP was classified graded as gr I (75K-150K/µL), gr II (50-75K/µL), gr III (25-50K/µL), and gr IV (<25K/µL). Follow up CBC were performed at 4 weeks.
Results: PI thrombocyte counts decline mean 84-88K/µL with courses 1-2 with about 15% of courses having PI thrombocytes less than 100K/µL. Gr I-II TP occurred in 34% (18/53) of first infusion courses and recovered by 4 weeks in 89% (16/18) of cases. Two subjects with mild baseline gr I TP experienced PI gr II transient TP (58 and 63K/µL) and recovered to baseline gr I TP (~140K) at 4 weeks. The second course had 20% (11/56) prevalence of gr I PI TP, with 2/11 still gr I TP at follow up. With courses 3-4, decline means were 61-66K/µL. Decreases in thrombocytes were slightly greater in those developing TP. Third and fourth courses showed 15% (9/59) gr I PI TP afterwards, and no TP occurred with the 5th, 6th or 7thinfusion courses (0/22). Symptomatic (purpura, bruising, bleeding) or Gr III/IV TP did not occur with any infusion in any course, up to 7 courses. Immediate PI monocytopenia occurred uniformly declining from mean 0.5/µL baseline to 0.1/µL immediate PI and recovered by 4 weeks with each course. Neutropenia did not occur PI; instead, neutrophilia was often present. Profound gr 4 lymphopenia was virtually always present.
Conclusions: Clinically silent TP occurs post ALE, usually mild gr I, short-lived, and presumably not due to a direct anti-CD52 action, as thrombocytes lack CD52 antigen but do have Fc receptors. TP at first course indicates it cannot be a delayed autoimmune TP. Decrease of thrombocytes and monocytes occur immediately PI, without evidence for clinical adverse events. PI TP may be an immune complex phenomenon (similar to that seen in rheumatic disease), and likely recover as ALE is eliminated and bone marrow responds. Transient gr I-II PI TP occurs in up to one-third of courses, slightly greater at the initial course, and the greatest degree of PI TP occurs in those with mild preexisting TP. In a small fraction of cases, the decrease in platelets could elevate risk of hemorrhage, especially if qualitative platelet defects happen to be present. Monocytopenia most likely reflects this same phenomenon and may also be in part a direct anti-CD52 cytotoxicity.
Disclosure: Funded in part by grant support from Genzyme-Sanofi