2009 Southern Regional Meeting Abstracts
Session: Hematology and Oncology I
Effect of rituximab therapy on NK and T regulatory cells in a patient with acquired Hemophilia A
Kruse-Jarres R, Ganapamo F, Leissinger C. Tulane, New Orleans, LA.
Purpose of Study: An 18 year old African-American woman who presented with peri- and post-operatively excessive bleeding following an appendectomy. She was diagnosed with a low titer acquired factor VIII inhibitor (antibody to factor VIII) and was treated with high doses (6000 units/hour) of factor VIII concentrate during the entire period of a complicated hospital course. On this regimen, she had good hemostatic control with normal range factor VIII levels, but this attempt of immune tolerance therapy (ITI) did not completely eliminate the inhibitor. Therefore, treatment with rituximab was initiated. Subsets of immune cells were studied.
Methods Used: During the course of the rituximab regimen, blood samples were collected immediately before the patient received each of four infusions of rituximab (on day 0, 26, 36 and 42). Peripheral blood mononuclear cells (PBMC) were isolated and multi-parameter flow cytometry analysis was performed. Fluorochrome-conjugated monoclonal antibodies specific for human cell markers were used.
Summary of Results: The factor VIII inhibitor disappeared after 4 doses of rituximab and factor VIII rose to a normal level. At day 0 the absolute count of CD19+ cells was 177 cells per milliliter (ml), on day 26 this value drop to 4.1 cells per ml, 87 cells per ml at day 36 and 1.8 cell per ml at day 42. Furthermore, at day zero the absolute number of NK cells (CD56+ CD16+) decrease from 488 cells per ml to 313 cells per ml at day 26, 234 cells per ml at day 36 and 149 cells per ml at day 42. Similarly, at day zero the proportion of T regulatory cells defined as lymphocytes from the CD4+CD25+ CD127+ low sub populations that are CD45RA- and Foxp3+ was 55.3%. This proportion decreases to 43.1 % at day 26, 40.2 % at day 26 and 39.7 % at day 42.
Conclusions: These results suggested that in this case, well beyond the expected B-cell depletion by rituximab, anti-CD20 therapy has a negative effect on NK cell absolute number and T regulatory cell proportion.
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