weaning off anti-rejection drugs?

[merryBe]

Hi, I found these new studies interesting and have a question.

we know the reason studies are going on is because the average TP lasts only 5-10 years....much of that due to the SOC rejection drugs.

what I find fascinating is why they think now folks can be weaned off!!

Is it because of cell division being affected by bone marrow stem cells?
In other words, when a liver cell does normal cell division, doesn't it just replicate the donor cell..but as more of the patients stem cells filter to the liver, over time does the liver turn over, or revert to more tissue of the recipients type?

I don't know the answer here, whether the immune system itself becomes more settled with donor tissue, or whether the tissue is changing.

that's why I'm asking. Does anyone know anything about this?  It would be really good news if this was part of it...especially for younger TP people.
mb

[merryBe]

foo....too tired to be posting

http://www.clinicaltrials.gov/ct2/show/NCT00135694?term=hcv&state1=NA%3AUS%3AWA&rank=16

this study also has a european arm, in Spain, but it seems the antirejection drugs increase the rate of destruction HCV causes in the new liver, so this is one study we may all wish to keep an eye on.

[mikesimon]

You said: "we know the reason studies are going on is because the average TP lasts only 5-10 years....much of that due to the SOC rejection drugs."

Before I take time to read the rest of your post where did you get this number - 5 - 10 years? And are you referring to organs in general, the liver, kidney, pancreas, small intestine, heart or what?

Mike

[IAmTheWalrus]

Thanks for the post. The study looks interesting. My AR drugs are toxic to the kidneys.

I have the same question as Mike has though. I was hoping, with regular oil changes, to get a few more miles out of mine?  :)

Brent

[mikesimon]

Operational Tolerance after Liver Transplantation

Last updated: 07 April 2008
Category: No Domain > No Category Assigned
authors Dr George Mazariegos
Synopsis
-

Sporadic clinical transplant tolerance has been achieved following solid organ transplantation, most commonly after liver transplantation. Operational tolerance, defined as long term (>12 month) freedom from all immunosuppression in patients with normal graft function was first seen in both non-compliant patients and patients withdrawn for emergent infectious or malignant indications ( 1, 2). Individual centers have also reported the ability to slowly wean patients from immunosuppression over time or emergently for specific indications after liver ( 3-5)   and kidney   ( 6,7) transplant.

For reasons that are unclear, patients transplanted as children have been more likely to achieve this operational tolerance than those transplanted as adults ( 3). Estimates of ability to wean immunosuppression successfully following liver transplant vary from 3-5% of cases ( 1).  In very carefully selected patient populations, up to 20% of patients may be potentially weaned ( 4). In live donor transplant populations, up to 15% of all patients may be successfully withdrawn from immunosuppressive medications ( 8, 9).   Long term follow-up of patients successfully withdrawn, however, is limited to individual center reports. The true incidence and ability to withdraw drugs after liver or other organ transplants is unknown as is the natural history of these patients after drug withdrawal.   A registry of these patients would allow better characterization of the natural history of drug withdrawal and help develop predictive clinical factors that favor drug withdrawal. Furthermore, this would facilitate entry of these patients into ongoing or developing trials of assay development. The development of predictive, reproducible assays ( 10) that can identify patients who may safely be withdrawn from immunosuppression or conversely identify those who require maintenance immunosuppression will be critical to minimizing long term morbidity and mortality in organ transplantation ( 11). Assays performed in this unique patient population, such as cytokine gene polymorphisms and dendritic cell subsets, have yielded encouraging but preliminary results ( 10, 12-14). Other centers have reported the importance of T regulatory cells as a potential mechanism in their tolerant patients and are identifying gene profiles associated with tolerance ( 8, 15).   The two largest single center experiences in drug withdrawal after solid organ transplantation are from Pittsburgh ( 4) and Kyoto ( 8, 9). The Pittsburgh experience has primarily focused on deceased donor transplantation. We currently follow 47 patients who have been withdrawn from immunosuppression after liver transplant by planned physician intervention (protocol), emergently due to infectious disease indications (mostly EBV or PTLD indications), as well as those who self-weaned medication but are still under medical supervision with laboratory assessments. As noted in Table 1 ( 4 ), most of these patients were children at the time of transplantation. Return to immunosuppression has been rare (1/48), no graft loss has occurred, and no chronic rejection has been documented. Mean time off immunosuppression is over 10 years in the prospectively weaned cohort.  

TABLE 1 Operationally tolerant liver transplant recipients University of Pittsburgh- long term follow-up (1992-2006)

Method of drug withdrawal
                                                    Protocol Emergent Non-Adherance
# Patients                                               28      13                6
Median Age at Tx (years)                       3.8      1.6                      11.4
Years from Tx to Wean                               5.7      3.13                     7.3
Years from Wean to drug cessation         2.2         N/A                 N/A
Mean Years off drugs currently                    10.8    11.7           17.1



The Kyoto group has documented 87 of 659 children (15%) who underwent live donor liver transplant between 1990 and May 2005 and have achieved complete withdrawal of immunosuppression ( 8).Taken in aggregate, predictive factors for successful drug withdrawal have included pediatric age at transplant, lack of autoimmune disease, and live donor transplant. A smaller cohort of 18 patients who underwent drug withdrawal at King’s College London England also demonstrated the positive predictive effect of non-auto-immune disease, as well as fewer donor-recipient HLA mismatches and low incidence of pre-weaning rejection history ( 16).

http://topics.scirus.com/Operational_Tolerance_after_Liver_Transplantation.html#

Mike

[mikesimon]

Sorry about the chart - I really wasn't trying to test your eye-mind coordination. I think you can handle it. Mike

[mikesimon]

Women Given Liver Transplants Outlive Male Recipients By Around 4 Years

ScienceDaily (Sep. 29, 2006) — Female liver transplant recipients outlive men given the same procedure by an average of 4.5 years, suggests research published ahead of print in Gut.


And while younger people tend to live longest of all, they also stand to lose more years of their life compared with those who have not had liver transplants, the research shows.

The research team assessed the life expectancy and years of life lost of 2702 people who had received a liver transplant