Rituximab in Refractory Idiopathic Thrombocytopenic Purpura (ITP).

Background. Rituximab, a chimeric anti-CD20 monoclonal antibody effective in B-cell depletion, may be useful in autoimmune disorders by interfering with the production of auto-antibodies.

Aims. To investigate the efficacy of Rituximab in patients with resistant ITP.

Patients and Methods. Fourteen adult ITP patients (3 males, 11 females; median age 44.5 years [21.1–67.6]) were treated with Rituximab (375 mg/m²/weekly for four doses). The median time between diagnosis and start of Rituximab was 2 years (0.2–33.1 months). All patients had already received at least two lines of therapy (median 3; 2–6): prednisone, pulsed high-dose dexamethasone, azathioprine, immunoglobulins, interferon or splenectomy. At the start of Rituximab, the median platelet count was 10 x 10⁹/L (3–20 x 10⁹/L). Response definitions: complete response (CR), platelet count ≥150 x 10⁹/L; partial response (PR), >50 <150 x 10⁹/L; minimal response (MR), >20 ≤50 x 10⁹/L; no response (NR) ≤20 x 10⁹/L. After completing therapy, patients were evaluated for platelet count after 1 and 3 months, and thereafter every 3 months until relapse or start of a different treatment. Peripheral blood B lymphocytes were evaluated by flow-cytometry as CD19+ cells before treatment, 1 and 3 months after stopping therapy, and then every 3 months up to recovery.

Results. One month after Rituximab therapy, 7 responses (2 CR, 4 PR, 1 MR; 50%) and 7 NR (50%) were observed. Two relapses occurred 5 and 18 months after response. The median follow-up of all treated patients is 6 months (1.8–34.6), while the median follow-up of all responsive patients is 6.1 months (2–18.7).

Before starting therapy, 11/14 cases were evaluable for flow-cytometry studies. The median baseline value of peripheral blood CD19+ B cells was 137 x 10⁶/L (58–476). One month after completing therapy, 7/9 evaluable cases showed absence of CD19+ cells and 2/9 showed a count of 9 and 4.4 x 10⁶/L CD19+ cells, respectively. At the last available control (median follow-up of 6.8 months; 1.9–32.5), 11/14 evaluable patients had still not recovered the baseline CD19+ cell count (median value: 5.5 x 10⁶/L; 0–287).

The following side effects were observed: 1 case of papulosquamous dermatitis, 2 cases of fever.

Conclusions. Seven out of 14 (50%) ITP patients had an early response to Rituximab (2 CR, 4 PR, 1 MR), that persisted in 5 cases. No late responses were observed. The response was independent of the post-therapy CD19+ cell numbers. No serious infections were observed during the clinical follow-up. No patient had to stop therapy because of severe side effects.