Rituximab is effective in the treatment of refractory immune thrombocytopenic purpura associated with chronic lymphocytic leukemia.

To the Editor: Two percent of chronic lymphocytic leukemia (CLL) patients present with immune thrombocytopenic purpura (ITP). Corticosteroids, immune globulins (IVIG) and splenectomy remain the mainstay of treatment for ITP. Rituximab is a monoclonal antibody against CD20 antigen expressed on B-lymphocytes. Because of its B-cell depleting capability, it has been employed in the treatment of autoimmune diseases. Many case reports and series have reported its efficacy in the treatment of refractory ITP. (1) However, its efficacy in CLL-associated ITP is not well known. Here, a patient with refractory CLL-associated ITP, successfully treated with rituximab, is described.

A 67-year-old female presented with rectal bleeding and ecchymoses on the extremities. Physical examination was unremarkable except for the ecchymoses. Colonoscopy revealed hemorrhoids. A complete blood count revealed a hemoglobin of 5.8 g/dL, white cell count of 29 X [10.sup.9]/L, platelet count of 13 X [10.sup.9]/L, lymphocytes of 52% and neutrophils of 45%. She was treated at another hospital with blood transfusion, prednisone 1.5 mg/kg/d and IVIG 0.4 g/kg/d for 5 days for presumed ITP without success. At our hospital, her blood smear showed anisopoikilocytosis, tear-drop forms, small lymphocytes, smudge cells and large platelets. Bone marrow biopsy revealed infiltration with [kappa]-restricted lymphocytes positive for CD5, CD19, CD20 (dim) and CD23 antigens. Megakaryocytes were abundant. A diagnosis of CLL-associated ITP was established.

She was started on high-dose methyl prednisone on hospital days 1 to 5 which was later switched to prednisone 1 mg/kg/d with no response. From days 10 to 18, she received two courses of IVIG, resulting in brief partial responses. Because of this, splenectomy was performed on day 22 which was later complicated by wound hematoma and dehiscence. Prednisone was discontinued. On day 27, her platelet count fell to 4 X [10.sup.9]/L and 4 courses of IVIG were given over the next 2 weeks achieving transient partial responses. On day 43, danazol (200 mg twice a day) and prednisonc (5 mg daily) were started, achieving a complete remission (CR) on day 52. However, on day 58, her platelet count fell to 47 X [10.sup.9]/L. She was started on rituximab 375 mg/[m.sup.2] for 4 weeks. Within 2 weeks she achieved a CR. Two months later, she remained in CR and switched her care to another hospital.

The current literature shows few cases of the effectiveness of rituximab in this setting. Patient 1 achieved CR in 1 week and the response duration was 6 months. (2) Three CLL patients with refractory fludarabine-associated ITP also responded. Patients 2 and 3 achieved CR and patient 4 achieved a partial response within 4 weeks. The duration of responses ranged from 6 to 17 months. (3) Patient 5 continues to remain in CR at 6 months. (4) A retrospective study reported its efficacy in 92 patients with refractory ITP, of which 14.1% have CLL. Although its efficacy in CLL-associated ITP was not reported specifically, the overall response rate for all patients was 55%. (5) These results suggest rituximab as an alternative agent, and therefore its role in ITP associated with B-cell malignancies should be explored (Table) further.

Thein H. Oo, MD

Caritas St. Elizabeth's Medical Center

Division of Hematology & Oncology

Boston, MA

References

1. Kazkaz H, Isenberg D. Anti B cell therapy (rituximab) in the treatment of autoimmune diseases. Curr Opin Pharmacol 2004;4:398-402.

2. Zaja F, Vianelli N, Sperotto A, et al. Anti-CD20 therapy for chronic lymphocytic leukemia-associated autoimmune diseases. Leukemia & Lymphoma 2003;44:1951-1955.

3. Hegde UP, Wilson WH, White T, et al. Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia. Blood 2002;100:2260-2262.

4. Jacoub J, Mchlayeh W, Tabbara I, et al. The use of anti-CD20 chimeric monoclonal antibody, rituximab, in adult patients with treatment refractory immune thrombocytopenia. [Abstract #3050] Blood 2004;104:74b.

5. Cabrera JR, Penalver FJ, Milan I, et al. Mabthera (Rituximab) in the treatment of 92 patients with refractory immune thrombocytopenic purpura. [Abstract #2074] Blood 2004;104:571a.

Published as an abstract in Blood 2004; 11: 74b, Abstract #3952.

Table. Summary of cases of refractory CLL-associated ITP successfully
treated with rituximab (a)

Patients     CR/PR              Onset of CR/PR  Duration of CR/PR

1            1st CR             1 week           6 months
             2nd CR (rituximab  unknown          3 months +
               retreatment)
2            CR                 4 weeks         17 months +
3            CR                 2 weeks          6 months +
4            PR                 4 weeks          6 months
5            CR                 unknown          6 months +
6 this case  CR                 2 weeks          2 months +

(a) CLL, chronic lymphocytic leukemia; ITP, immune thrombocytopenic
purpura; CR, complete remission, PR, partial response.