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Alert Number 288

At last! Some one did the Rituxan experiment that needed to be done

Date: July 25, 2008

Once in a while I come across an article that makes my day. Here it is, for your reading pleasure as well.

There is little doubt that Rituxan is one of the most important CLL drugs to come on the scene in the recent past. Many of us have tried it as a single agent, and when that stopped working, reluctantly moved on to combinations of Rituxan with more dangerous chemotherapy drugs such as fludarabine, cyclophosphamide, high dose steroids (FR, FCR, R+HDMP).

But it has long been known that the body’s complement system is an integral part of what makes Rituxan work. Poor complement levels or deficiencies in key components of the complement system can cause failure of Rituxan therapy. So, it is not a big stretch of the imagination to suggest that Rituxan therapy can possibly be made to work better if we goose it along with an extra dose of complement.  Where do we get human complement? Very simple, from fresh frozen plasma – obtained readily from blood donations. Fresh frozen plasma is no harder to get and no more expensive than commonly used blood products such as red blood cells, platelets etc.

In this admittedly small and exploratory experiment, five patients with severe treatment resistant CLL, were treated with two units of fresh frozen plasma (read: hefty dose of complement) along with the standard dose of Rituxan.  Bear in mind, these were all patients who had failed Rituxan earlier on, and all of them had already been treated with fludarabine. Chances of any of them responding to single agent Rituxan were next to zero. So, how did these guys fare when the Rituxan was given along with a good dose of complement in the fresh frozen plasma?

All of them responded, vigorously so. Lymphocyte counts in the blood dropped markedly, lymph nodes and spleen shrank, anemia and thrombocytopenia (low red blood cells and platelets) improved.  And the researchers saw no reason why this could not be repeated with additional cycles over time, as necessary.

Wow.  Who would have thunk it, some one actually doing the rational experiment to see if addition of complement boosts Rituxan’s killing power. We have been advocating this for several years now on CLL Topics website.  Rejoice, all ye Rituxan fans. Now all you have to do is try and convince your local onc to give you some fresh frozen plasma prior to your single agent Rituxan infusion.  Kidding aside, I hope this very small trial will be followed up by larger and more controlled trials to verify the encouraging results seen here.

Be well,




QJM. 2008 Jul 23.

Adding fresh frozen plasma to rituximab for the treatment of patients with refractory advanced CLL.

Klepfish A, Rachmilewitz EA, Kotsianidis I, Patchenko P, Schattner A.


From the Blood Bank and Haematology Department, E. Wolfson Medical Centre, Holon, The Haematology Department, Democritus University of Thrace School of Medicine, Alexandroupolis, Greece and The Hebrew University Hadassah Medical School, Jerusalem, Israel.

BACKGROUND: Many patients with chronic lymphocytic leukaemia (CLL) develop progressive, treatment-resistant disease. Rituximab (RTX), a monoclonal antibody targeting CD20 on B lymphocytes and widely used in other indolent B cell neoplasms is less efficacious in CLL, possibly due to associated complement deficiencies. Objective: To examine in open trial whether providing complement by concurrent administration of fresh frozen plasma (FFP) will enhance the effect of RTX in CLL. Setting: Outpatient haematology clinics in Israel and Greece. Patients: Five patients with severe treatment-resistant CLL. All had been previously treated with fludarabine and three also failed treatment with RTX. Intervention: Two units of FFP followed with RTX 375 mg/m(2) as a single agent, repeated every 1-2 weeks, as needed. RESULTS: A rapid and dramatic clinical and laboratory response was achieved in all patients. Lymphocyte counts dropped markedly followed by shrinkage of lymph nodes and spleen and improvement of the anaemia and thrombocytopenia. This could be maintained over 8 months (median) with additional cycles if necessary. Treatment was well tolerated in all cases. CONCLUSION: Adding FFP to RTX may provide a useful therapeutic option in patients with advanced CLL resistant to treatment.

PMID: 18650226 [PubMed - as supplied by publisher]


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