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Alert Number 225

Treating Autoimmune Disease: ITP and AIHA in CLL

Date: April 1, 2007

CHOP and R-CHOP are important therapy combinations in non-Hodgkin’s lymphoma. It is important to know what R-CHOP is, what drugs are involved, and what to watch out for when using this combination. Variations on the R-CHOP theme are sometimes used to treat CLL.

R: Rituximab (“Rituxan”). Monoclonal antibody that targets CD20 marker on mature B-cells. If you have never heard of it, it is really important that you start reading!

C: Cyclophosphamide (“Cytoxan”). Alkylating agent (similar to chlorambucil, “leukeran” , one of the older CLL drugs. It is a component of the FCR combo pioneered by M. D. Anderson.

H: Doxorubicin (hydrochloro “Adriamycin”). Dox and its sister compound mitoxantrone are known to be heart unfriendly. People with poor cardiac function need to be monitored and evaluated carefully before using it.

O: Vincristine (“Oncovin”) Vincristine is one of the famous alkaloids obtained from the plant vinca. It is used frequently in breast cancer. You need to be aware that vincristine can cause peripheral neuropathy (tingling, nerve pain, loss of feeling). Sometimes the letter “V” is used instead of “O” for vincristine, as in CVP (cyclophosphamide, vincristine and prednisolone) instead of COP.

P: Prednisolone. Gluco-corticosterioid drug. We have discussed it many times on our website. It is very potent as an immune system suppressor, a necessary thing when fighting autoimmune disease. But for the same reason, it is also a risk factor for opportunistic infections.

The reason I am writing about R-CHOP is to bring to your attention an interesting abstract in last year’s ASH conference. RCD is a truncated version of R-CHOP, without the pesky heart problems associated with doxorubicin, and no vincristine either to cause worries about peripheral nerve damage. Prednisolone has been replaced by dexamethasone (“Decadron”), a steroid that you take as an oral pill. While the sample size was small, only 18 patients, it nevertheless is an interesting study. It shows that the RCD combination is effective in treating AIHA and ITP, and that it is possible to re-treat the patients once they relapse. In keeping with our understanding of the “slippery slope” analogy of CLL, second remissions are shorter, but still quite respectable.

I like this approach a lot better than the R-CHOP or R-COP combos for treating CLL patients with autoimmune disease. Considering its origins in Long Island Jewish Hospital with Dr. Rai as one of the authors, you should not have a problem bringing this option to the attention of your local oncologist. Vincristine is an iffy choice in CLL, and dox is not exactly something I would ask for in my Christmas stocking. Doing our best to weigh risks versus rewards once more, RCD is a good compromise between efficacy and reduced toxicity. I would be interested to know if any of your local guys have comments on this combination.

Be well,



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.

Session Type: Poster Session, Board #61-III

Matthew S. Kaufman, Yehuda Z. Lebowicz, Nancy Driscoll, Christina Johnson, Dale Janson, Angelica Caramanica, Rajasree Roy, Neetu Radhakrishnan, Dhaval Mehta, Mark Hoffman, Dilip Patel, Nina Kohn, Kanti R. Rai.

Hematology-Oncology, Long Island Jewish Medical Center, New Hyde Park, NY, USA; Biostatistic Unit, Feinstein Institute for Medical Research

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.

Hemoglobin response to RCD
Hemoglobin Measurements N Mean Hgb
Std. Dev. Min. Hgb g/dL

Max Hgb


Hgb at start of episode 1 17 8.1 2.1 4.0 12.1
Hgb at end of episode 1 17 13.2 1.4 10.0 15.4
Hgb delta episode 1 17 5.1 2.3 1.7 10.2
Hgb at start episode 2 9 8.4 2.3 5.3 12.2
Hgb at end episode 2 9 13.5 1.4 12.3 16.6
Hgb delta episode 2 9 5.1 2.1 1.4 7.7

Post-treatment Coombs status and response duration
Coombs Status 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 13 7.1 (range 3-12)

This abstract appears in Blood, Volume 108, issue 11, November 16, 2006


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