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Fatal complications of autologous cell therapy

Does anyone can wonder what the complications could be if you injected yourself with your own cells? They would not cause an immune response and should have no “tumor-forming ability”. Nevertheless, as the field of clinical cell therapy matures and develops, we are starting to see some cases of cell therapy complications. I’d like to focus only on autologous cell therapy – the least expected kind, able to yield any complications. Ok, now some recent examples:

1. Cardiac cell therapy
Ventricular fibrillation following autologous intramyocardial cell therapy for inherited cardiomyopathy [1]

A 41-year-old male with cardiomyopathy from an inherited beta myosin heavy-chain mutation underwent treatment for heart failure with intramyocardial cell transplantation. He received direct injections into his heart of autologous precursor cells isolated from his blood.

The patient traveled overseas to undergo autologous peripheral blood cell harvest followed by direct myocardial injection of autologous precursor cells (APCs) as a means of augmenting heart function.

There were 12 injections in the anterior wall and 18 in the lateral and inferior walls. Approximately 60 min after intramyocardial injection, he developed ventricular fibrillation that required defibrillation.

He was rescued but developed renal failure and a number of arrhythmias. A few months later he developed more complications, including right hemothorax and hemorrhagic stroke, which was fatal.

But how common this complication in cell therapy of cardiomyophaty? In discussion authors cited one of trials [2]:

One study reported APC transplant in 39 cardiomyopathy subjects including 5 with nonischemic cardiomyopathy. Of note, 7 of 39 developed ventricular fibrillation during thoracotomy and open intramyocardial injection similar to the procedure used in this patient. Of the seven subjects with arrhythmias, two developed intractable, lethal ventricular tachyarrhythmias, although the findings do not distinguish between the type of underlying cardiomyopathy.

in conclusion:

Given the limited rationale for the use of bone-marrow-derived or circulating cell therapy in inherited cardiomyopathy, coupled with the potential danger associated with direct injection into a myopathic and arrhythmogenic ventricle, we encourage caution with cell-based therapy when viable alternatives including heart transplantation are present.

2. Adoptive T-cell therapy
Case report of a serious ddverse event following the administration of T cells transduced with a chimeric antigen receptor

More than 10 clinical trials evaluating second- or third-generation CARs (chimeric antigen receptors) are currently listed on ClinicalTrials.gov, and there is some encouraging preliminary evidence of clinical efficacy.

However, in this issue of Molecular Therapy [3], two recent serious adverse events (SAEs) are reported in subjects enrolled in these trials, raising concerns about these receptors. The first event, described by Morgan and colleagues at the National Institutes of Health (NIH),occurred in a patient with widely metastatic colon cancer who received more than 100 billions T cells modified with a CAR targeting HER2 containing two costimulatory moieties (CD28 and 4-1BB) after intensive lymphodepletion. The subject developed pulmonary toxicity within 15 minutes in association with very high cytokine levels, followed by cardiac arrest, and died 4 days later. After extensive investigation and analysis of autopsy specimens, the investigators concluded that the toxicity may have been due to targeting of low levels of HER2 on pulmonary endothelium by transgenic T cells.

About the second “CARs case” read here [4].

Right now we don’t know what kind of adverse effects and complications to expect from cell therapy procedures – autologous or allogeneic. There are hundreds of clinical trials going on and we are so eager to see the results of each phase. I feel like not all cases of cell therapy complications are reported in literature or in conferences. I think everything should be reported right away. Clinical case reports usually get published relatively quickly after submission. If we will get to know about all possible complications, as soon as they come up, we can avoid them in future and design new trials, based on this knowledge.

I have an idea about informational resource combining all reports of severe adverse events and complications of cell therapy. Creation and maintenance of such a database will be a great help for all professionals pursuing the impact of cell therapy in modern medicine. If you would like to make this project alive, please contact me.