How should proliferative glomerulonephritis with crescent formation be treated in young women with SLE? Will low-dose pulse cyclophosphamide (Cytoxan) and/or mycophenolate mofetil (CellCept) do the job while preserving fertility?

Decision-making in such young women can be difficult and among the most agonizing - for both patient and physician. It usually requires a very prolonged conversation with the patient and her immediate family, whether parents or significant other. While such women clearly need treatment - and preservation of fertility is obviously desired - it is very difficult to know the best option.

We use one of three options in these circumstances:

1. administer full-dose cyclophosphamide (with prednisone) and hope for the best;
2. administer prednisone and mycophenolate, although there is a little controversy as to whether this is as effective as cyclophosphamide; or
3. pretreat the patient with leuprolide acetate (Lupron) and administer prednisone and cyclophosphamide, although it makes young women pretty miserable and it must be continued for the full duration of treatment.

None of these options is ideal. The usual solution is number 2.

Low-dose cyclophosphamide would not be helpful. The Europeans (English and French, in separate investigations) have published on "low-dose" cyclophosphamide in uncontrolled trials, but their definition of low-dose is 0.5 g per meter squared every two weeks, rather than the NIH protocol of 1.0 g per meter squared every month - so I don't get the point of it all. It seems to me the total cyclophosphamide dose is more or less the same, and they have provided no additional data regarding fertility or other critical information.