Transplants are more likely to be rejected in CLL than in other conditions. The rejection rate in follicular lymphoma is between 3 and 6%. For CLL it may be as high as 20%. One study from Nebraska showed that the the graft failed to take completely in 35% of cases. This particularly a problem with T-depleted grafts - rejections of close to 20% compared with less than 10% with unmanipulated grafts. Factors that might play a part in this are the level of CLL infiltration in the marrow and a deficiency of host dendritic cells.
Another specific factor for CLL transplants is prior immunodeficiency. 60% of non-relapse deaths are due to infection. Patients who have had prior fludarabine or alemtuzumab are particularly susceptible.
For patients with mixed chimerism (both donor and graft cells are present in blood or marrow) and especially if there is evidence of persistent disease, donor lymphocyte infusions are indicated, though they are usually ineffective in progressive disease. Graft-versus-host disease is of course a risk of DLI and they have found greater favor with units using T-depleted grafts.
Another particular feature of CLL transplants is the occurrence of late relapses. One possible reason for this seems to be the existence of the CLL in sanctuary sites that do not communicate with blood or marrow - blood and marrow being the sites that are tested for minimal residual disease. Imaging studies for lymph node involvement are therefore necessary post transplant before declaring cure.
6 comments:
Doc,
What happens exactly when a graft is rejected? Does the patient just die? Can he have another graft? Can he still try another donor, as if he has two siblings that are both matches?
It varies. Some patients remain fairly disease free with not much marrow, some die, some get a second transplant successfully.
I've wondered about sanctuary sites. If the cll is confined to the marrow, the blood, or other specific sites generally and not throughout all the other parts of the body, why would it settle in a sanctuary site?
I mean, we have nodes all over the body, but cll is usually in only some of them (I understand), so why would a disease of the lymphatic system not be in all of it and yet be in some sanctuary site?
In the old days, they used to cure people sometimes by cutting out the infected nodes, didn't they?
CLL is usually in most of the nodes even if they are not enlarged, but as has recently been posted on ACOR, it can be in the prostate. Perhaps because of permeability or lack of effectore mechanisms, the CLL might be more dificult to kill than in teh blood and marrow. I don't think CLL has ever been cured by cutting out a lymph node.
Doctor Hamblin,
I am surprised and dismayed by the high level of rejection. I lost my graft even though I was MRD negative at the time. I think it was because I had no F before the HSCT until I had FRC for conditioning in the week before (Dr. Khouri's protocol), but I got no ATG.
As I am heading towards a second transplant for my CLL/ITP any advice is most welcomed
Be well
Brian Koffman MD
I was thinking of you, Brian, when I wrote it. We don't really know why the graft gets rejected. The recent Spanish series reported 9% using fludarabine + melphalan, and the British group which used the same conditioning plus Campath found 12%. Often using a bigger dose of the graft enables it to take. The problem may be insufficient dendritic cells, which may be a feature of CLL.
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