Part 17 of IVD Hall of Fame
Heart transplants have become rather commonplace – particularly here in the US – ever since Dr. Barnard performed the first one back in 1967. Yet while the procedure may be somewhat "routine", the path to recovery for a transplant patient is not without its difficulties.
Allograft rejection is always a possibility for any patient that has received a heart transplant. As a result, patients that undergo heart transplant will likely remain on anti-rejection medications for their entire lives. However, most physicians will reduce the levels of transplant medications like Prednisone or Cyclosporine if they consider the risk of rejection to be low. The reason is simple – many of these transplant medications have nasty side effects such as kidney failure, elevated risk from infections, and osteoporosis, to name a few.
Unfortunately, the best way to determine acute cellular rejection (ACR) until rather recently was through biopsy. This procedure, though relatively safe, is invasive and not very pleasant. It involves a catheter, a bioptome, a neck vein, and…well you get the point. The first 6 - 12 months post-transplant are critical, and since the most patients are asymptomatic in early rejection, biopsies during this period can be rather frequent.
But the real issue with heart biopsies is that the resulting pathology reads can be vague, or sometimes even wrong, and depend greatly upon the pathologist. Grade 3A or higher (major rejection) is usually pretty accurate. But from there, whether a patient is showing the signs of mild to moderate rejection, or no rejection, depends on the skill and training of the pathologist, and the quality of the biopsy slides they are reading.
Echocardiographs can help clarify the picture, by identifying dysfunction associated with ACR, but irregularities in an ECG don’t always mean ACR. The same is true for heart catheterization, which measures the chamber and vascular pressure in the heart.
Entering into this murky clinical setting was the AlloMap test, introduced by XDx as a laboratory developed test in 2005. The RT-PCR based blood test measures expression of 20 genes: 11 for ACR and 9 “housekeeping” genes. In 2008 the test was cleared by the FDA as a 510(k) de novo, being one of the few LDTs cleared using the IVD MIA guidance issued by the agency in 2007.
The test has a very high negative predictive value (>98%), which simply means that a low risk score on an Allomap test equates to a low risk of rejection. This is good news for patients, as it can also translate to fewer biopsies and – more importantly – lower dosages of anti-rejections medications, thereby greatly improving their long-term prognosis.
The Allomap test is an example the next generation of IVDs, tests that don’t just diagnose diseases, but provide useful clinical information on the risk of recurrence or drug efficacy. And while these tests might not all be commercial blockbusters or household names, their value to the patients that they serve is reason enough to place them in our hall of fame.