A Combination of Rituxan, Cyclophosphamide and Dexamethasone (RCD) Results in Long-Lasting Responses in Autoimmune Anemia and Thrombocytopenia in CLL Patients: A Single Institution Study.
Authors: Kaufman Matthew S. , Lebowicz Yehuda Z. , Driscoll Nancy , Johnson Christina , Janson Dale , Caramanica Angelica , Roy Rajasree , Radhakrishnan Neetu , Mehta Dhaval , Hoffman Mark , Patel Dilip , Kohn Nina , Rai Kanti R. 
Published: October 2019

Coombs positive hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) are well-known complications of chronic lymphocytic leukemia(CLL). Both are autoimmune phenomena thought to be byproducts of the immune system dysregulation manifested in patients with CLL. Rituxan, cyclophosphamide and dexamethasone(RCD) are known to effectively target lymphocytes and inhibit autoimmune processes. We present our data analyzing 18 CLL patients with one or both of these autoimmune processes treated with the RCD regimen between 1998 and 3/2006. These patients consisted of 15 with AIHA alone, 2 with both AIHA and ITP and one with ITP alone. The RCD cycle consisted of rituximab 375mg/m2 iv infusion given on day 1, cyclophosphamide 750–1000mg/m2 iv (depending on CLL tumor burden) on day 2, and dexamethasone 12 mg iv on days 1 and 2, and orally days 3 through 7. These cycles were repeated at intervals of 3–4 weeks, depending upon recovery of blood counts. All 18 patients responded to treatment in terms of hgb, platelets or both. For the first episodes of AIHA (n=17) mean starting hgb was 8.1g/dL (range 4.0–12.1) and mean post-treatment hgb was 13.2 g/dL(range 10.0–15.4)(Table 1). The three patients with ITP had a platelet increase from nadirs of 1,000, 1,000 and 14,000 to 408,000, 161,000 and 135,000, respectively. Mean duration of initial response was 22 months (range 6–41). Nine patients relapsed and were retreated with RCD. Again, all 9 responded, and had a mean increase in hgb of 5.1g/dL (range 1.4–7.7) with a mean duration of second response of 16 months(range 3–33). Overall, median survival from initiation of RCD was 70 months (95% CI; 46 to an upper limit not-yet determinable, with follow-up to 8/2006).

Of 8 patients with post-treatment Coombs data available for the first episode of AIHA, 4 (50%) converted to Coombs negativity (Table2) and had a mean duration of response of 23.0 months (range 12–41) vs 8.8 months for those who did not convert(range 6–11). In all AIHA episodes (including repeat episodes) with post-treatment Coombs data available (n=18), 6 of 18 (33%) converted to Coombs negativity. The mean duration of response was 19.8 months (range 6–41) for all episodes with conversion to Coombs negativity, vs 7.0 months for those without(range 3–12). This finding that Coombs conversion portends a longer duration of response suggests treatment goals for AIHA should be a conversion to Coombs negative, and not stopped with recovery of hgb.

Table 1. Hemoglobin response to RCD N Mean Std Deviation Min Hgb Max Hgb at start episode 1 17 8.1 g/dL 2.1 4.0 g/dL 12.1 g/dL Hgb at end episode 1 17 13.2 g/dL 1.4 10.0 g/dL 15.4 g/dL Hgb delta episode 1 17 5.1 g/dL 2.3 1.7 g/dL 10.2 g/dL Hgb at start episode 2 9 8.4 g/dL 2.3 5.3 g/dL 12.2 g/dL Hgb at end episode 2 9 13.5 g/dL 1.4 12.3 g/dL 16.6 g/dL Hgb delta episode 2 9 5.1 g/dL 2.1 1.4 g/dL 7.7 g/dL Table 2. Post-treatment Coombs status and response duration N Mean duration of response (in months) Post-treatment Coombs negativity in episode 1 4 22.2 (range 12-41) Post-treatment Coombs positivity in episode 1 4 8.8 (range 6-11) Post-treatment Coombs negativity in all episodes 6 19.8 (range 6-41) Post-treatment Coombs positivity in all episodes 12 7.1 (range 3-12)