Re: Fludarabine causes AIHA in husband ....Dr. Rai's RCD

[Guest guest]

When I was helping to run LRF CLL4 we were faced with this problem of fludarabine induced AIHA. Our advice was to put a patient on cyclosporin. The dose needed is rather less than is used for prevention of allograft rejection or GVHD protection and would aim to kep a blood level of about 100. The theory behind it is that the AIHA is a consequence of failure of the CD4+, CD25+ regulatory T cells, which are extremely sensitive to fludarabine. These cells control the autoimmune process and it seems that cyclosporin supplements this function. We found that while the patient remained on maintenance cyclosporin it was possible to introduce other treatments. If not even a simple alkylating agent like bendamustine or even chlorambucil will trigger another attack of hemolysis.

Anti-CD20 antibodies of any sort will kill normal B cells and this lower normal serum IgG, though normal B cells do recover over time when the anti-CD20 antibodies are withdrawn. This is one of teh potential hazards of maintenance rituximab.

Treatments that would be safer after AIHA include high dose steroids and revlimid, and possibly cyclophosphamide,

Terry

In a message dated 08/10/2010 23:42:40 GMT Daylight Time, heartsong11@... writes:

Dear Terry, in regard to your answer below, could you be more specificas to how cyclosporin gives "cover" to bendamustine? I am also SOcurious as to why you say that maybe any other treatment 'shusband has after he recovers may trigger another AIHA episode. Isthe immune system then just "turned on" and more wary? I feel this iswhat has happened to me even though I got AIHA 7 years into CLL beforeany treatment. It got quite a lot worse when we tried out PCR and hadto stop after one cycle when I had runaway hemolysis.I then saw Dr. Rai and did 5 months of his RCD which helped but stilldidn't completely stop hemolysis but it did seem like the best answerfor a pretty crazed immune system. I am now finishing up with theentire 6 months of Arzerra which unfortunately is giving me some nastyside effects like neuropathy. Hopefully that will abate when thedrug is discontinued in 4 months. It is keeping the hg up better, butas we moved from the weekly to the once a monthly Arzerra, the hg isdropping again. But Arzerra (or also the RCD?) has also lowered ALLmy gammaglobulins well beyond the low they were at before. Do Rituxanand Arzerra in killing the B-cells wipe out most of thegammaglobulins? I am thinking if the A doesn't keep the hg up, I willprobably have to try RCD again and wonder if it does some kind of"conditioning" to the immune system that helps it go back to normal,very unlike other combinations of chemos.My doc was also told by Dr. Rai that he had seen Bendamustine causeAIHA in some instances and so did not recommend it for me. And Dr.Rai told me that he had seen people whose AIHA got worse doing PCR orFCR, even in combination, like me. He is not in favor apparently ofusing purine analogs with people dealing with AIHA. Clive Zent ofMayo argues adamantly against using them with AIHA. Again, we are allso different.I hope you are hanging in there through all of what you are goingthrough. Best to you, all my prayers and thoughts to you, Carol4b. Re: Fludarabine causes AHA in husband ..Dr. Hamblin?Posted by: "TERJOHA@..." TERJOHA@... terryhamblinDate: Thu Oct 7, 2010 5:32 pm ((PDT))I was the one who first discovered that fludarabine caused hemolyticanemia. It is possible that when your husband recovers almost any treatment willretrigger another episode. In my opinion the best remedy is the Kanti Rairegimen that involves steroids, cyclophosphamide and rituximab. He mightalso find that cyclosporin is helpful. It is very unusual for FCR as opposedto fludarabine alone to cause AIHA; in the recent German trial it was lessthan 1% of cases.Bendamustine is almost certainly contraindicated unless it is given withcyclosporin cover. DR Byrd is an expert on fludarabin-induced AIHA and heshould be able to advise you.Terry Hamblin MD--