The future of organ transplantation

Since the mid-seventies, hematopoietic stem cells from bone marrow or peripheral blood have be transplanted for the treatment of various diseases.  Indications for haematopoietic stem cell transplantation include acute myeloblastic leukaemia, malignant lymphoma and myeloma².

Today, over 50,000 haematopoietic stem cell transplants are carried out every year around the world¹. But, despite how many transplants are carried out, challenges still remain due to its high mortality rate, needed improvements in diagnostic testing and limited therapeutic options.

Various treatments currently exist and are in trials for organ rejection in haematopoietic stem cell transplantation. There are also various new technologies being developed that can help diagnose and treat transplant organ rejection.

Haematopoietic Stem Cell Transplantation

Tepadina from Adrienne SRI and in the US Amneal, BioScience was approved in the EU and US in 2013 to reduce the risk of graft rejection when used with older drugs Busulfan + cyclophosamide as a regimen for allogeneic haematopoietic stem cell transplantation in paediatric patients with class 3 Beta thalassemia. There is a generic version on the market.

Approved in the EU in 2019, Trecondi (treosulfan) from Medac GMbH is intended as a “conditioning” treatment prior to allogeneic haematopoietic stem cell transplantation to improve the rate of survival after two years. Medac has received guidance from the FDA that as a 505(b)(1) NDA, no additional clinical study will be requested for US Marketing Authorization. Approval in the US expected in 2021.

Uvadex (methosalen) + Therakos Cellex Photopheresis system from Mallinckrodt to treat steroid resistant and steroid intolerant GVHD in adults following allogeneic hematopoietic stem cell transplant was approved in Australia in September 2016 as well as for treatment of cutaneous T Cell Lymphoma.

NiCord (omidubicel) from Gamida Cell is in Phase III trial to report in H1 2020 to treat Bone Marrow Transplant Patients via stem cells. Despite the curative potential of bone marrow transplant, treatment is not always effective in the US and more than 40% of patients do not receive a transplant. Omidubecel offers a therapeutic dose of stem cells to meet this challenge. The median time to neutrophil engraftment was significantly shorter for patients on omidubecel. If trials succeed the company plans to submit the biologics license application to the FDA in the second half of 2020.

Future treatment

One vital need is to develop improved diagnostic tests that can pick up signs of rejection at an earlier stage, such as cell-free DNA technology. Another important route is to find procedures that can induce immune tolerance which would help eliminate the need for immunosuppression.

Meanwhile, a number of novel approaches are under investigation to tackle side effects of current immunotherapies: for example, combination therapy with drugs can be used to treat the neuropsychiatric side-effects, and blood purification therapy have shown itself to be effective against neurotoxicity in some cases.

Another of the emerging areas of new treatment is the reformulation of current therapies using nanotechnology which offers the potential to increase the opportunities for localized drug delivery, raise drug solubility and minimise toxicities. This can also offer new opportunities for pre-treatment of organs prior to transplantation, to allow the use of allografts, or to protect from ischemia-reperfusion injury³.