A systematic review was designed to analyze all the early experiences of DLT in trasplantology and was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (16). The protocol of this systematic review was registered in PROSPERO (CRD42022316661). A systematic literature search of Medline, Web of Science, and Cochrane databases with the following search string: (“blockchain” or “distributed ledger technology”) AND (“transplant” OR “graft”) was carried out on 29th April of 2022, and additional manuscripts were retrieved from reference lists of included studies and relevant reviews. Moreover, a grey literature search was performed through Google to find other resources available.

Results have been imported in Mendeley 1.19.8 (Elsevier, Netherlands) to remove duplicates. Bibliographic citations of included studies have been manually searched to identify other studies that filled the review’s inclusion criteria.

Two reviewers (MM and MP) worked independently to screen the titles and abstracts of identified citations, and subsequently, the full texts of potentially eligible studies. Disagreements between reviewers were resolved by discussion and with the help of a senior adjudicator (AA).

Eligible studies were all English manuscripts regarding DLT application in organ and tissue transplant, even partially. Manuscripts regarding other specialties were excluded from the study.

The systematic search strategy identified a total of 13 publications that were included in the narrative review (Figure 4). None of the publications enlisted were registered as clinical trials. Therefore, due to the lack of a clinical outcome and paucity of data, a narrative review was designed to underline both already designed and putative future applications of DLT in transplant care.

Organ allocation systems encompass all the processes involved in organ distribution across a region to ensure fair and ethical distribution across patients on the waiting lists (18, 19). The importance of ethical organ allocation lies in the huge number of patients in the waiting list; it has been calculated that every 12 min a new name is added to the organ waiting lists and that an average of 21 patients die due to lack of organ availability every day (21). Due to the increasing demand for organs and the inadequacy of organ procurement, every country designs its own allocation rules trying to balance inequality among patients (utility model) and transplant benefit (net life-years gained) (19).

For instance, in Italy, deceased kidney donor allocation includes a regional level where several factors such as waiting time, age, human leukocyte antigen (HLA) match, % of panel reactive antibody (PRA), defined regional-based or national-based renal urgency, combined transplant, and pediatric priority are taken into consideration (18).

Another example of deceased organ allocation is the model for deceased liver distribution among countries in the Eurotransplant program. In the Eurotransplant model, liver donors are allocated first internationally to high urgency status patients or to those with an approved combined organ status, and then on a national basis, where allocation is recipient-driven or center-driven, depending on local rules (27). In the latter case, “match MELD,” AB0 blood group rules, predefined center, and donor profile criteria (age, weight, virology, split, etc.) for a particular recipient, and time from the listing are all taken into account prior to organ offering (27). “Match MELD” consists of the highest value between “lab MELD” or “exceptional MELD.” “Lab MELD” is calculated according to the Model for End-Stage Liver Disease (MELD) (28) with international normalized ratio (INR), bilirubin level, and serum creatinine. The latter, exceptional MELD, can be requested under certain circumstances when patient severity is not well described by lab MELD with the disease list repeatedly revised (27).

However, despite the wide application of complex allocation system, in some countries, the lack of a connecting platform could ease illegal practices or illegitimate methods in some hospitals (14). It has been calculated that 5%–10% of kidney transplants performed annually are currently through illegal practices, such as organ trade, and organ tourism (29). Moreover, illegal organ donation lacks all the preoperative assessment of recipient and donor to reduce possible side effects, oncological and infective risks (30, 31). Under these circumstances, fair organ allocation is an ethically compelling need in order to prevent harm to patients and on transplant program reliability worldwide.

Hence, DLT technology could provide a useful tool to resolve these issues, providing an efficient, secure, distributed, trackable, and immutable framework to promote organ allocation and donation (14, 21). Firstly, the DLT model through decentralization and without a centralized source could determine a sharing model to cope with such security threats and anonymity of data transactions (21, 22). A possible model for DLT in organ allocation and listing may be represented by a permissioned blockchain network where regulatory authority can easily control the access in the network. Permissioned blockchain rely on a governance structure (in this case regulatory authority) that controls access and enforces rules. In this specific blockchain network commonly are implemented alternative computationally intensive consensus mechanisms compared to PoW, because of the degree of trust among the different nodes. In a permissioned DLT, regulatory authority, as in centralized network, are in charge of responding to incident including cyber threats and as in a centralized network they can control access (13).

Due to the nature of the DLT, this model could determine other advantages in the organ procurement process in terms of auditability, which is immutable and can be easily reviewed by government auditors (22). However, while some authors may argue that the immutability of DLT could represent a limitation of this system in case of data entry errors, eventual data entry error may be correct by regulatory authority in private/permissioned blockchain (15). Moreover, Data entry error may be easily reduced by application of Internet of thing (IoT) technology, and machine-to-machine communication (M2M) (21). IoT is defined as a network of physical things linked to each other by means of the Internet (32), while M2M is a particular system where machines communicate without human involvement, avoiding human manipulation and securing organ allocation system (21). In fact, some of the above-mentioned organ allocation systems require biochemical variables such as PRA, INR, and bilirubin level, which can be updated directly from the laboratory in the distributor ledger, while clinical variables could be updated by medical wearable devices (21, 33), or radiological or radiomics variables could be directly uploaded from Picture archiving and communication system (PACS) (Figure 5). Finally, another potentiality of DLT decentralized nature is the lack of TTP institution for its legitimacy, leading to a real international DLT-based organ procurement network, not restricted to national borders (22). Table 3 describes the pros and cons of different systems to manage organ allocation in a centralized network, public DLT, and private/permissioned DLT (23).

Limitations of the current application are social perceptions about DLT in the medical fields, the possible conflict with European legislation, and the lack of standardization of EMR among different facilities (34). In fact, despite the promising application of DLT technology in the Estonian NHS, application of DLT in EMR is limited and scares, therefore further evidence are needed. Regarding the latter limitation, EMR standardization among different facilities could promote some benefits in terms of sharing information between different centers, and enhancing medical information migration between different providers besides transplantation (22). Finally, European privacy legislation may represent a limitation for the implementation of DLT technology in medical information technology. The General Data Protection Regulation (GDPR) is a European Union law applied from May 2018 to safeguard personal data, and privacy of European citizens (35). GDPR regulation, which was written when DLT were mostly used in cryptocurrencies and their further application were not applied in medical or other uses, introduces the “right to be forgotten” (13). In order to solve this dilemma several authors and companies are currently working to solve this paradox, with different solutions from a legal agreement between participants in a private/permissioned blockchain or improving anonymization of the data in the DLT (13).

Despite the application of expanded criteria, deceased donors or marginal kidneys in dual kidney procedures (36, 37), it has been calculated that fewer than 25% of the waitlisted patients are transplanted because of organ shortage (38). To overcome the chronic organ shortage, kidney donation is routinely performed in one-third of patients from living donors. Moreover, besides increasing the donor pool, kidney donation from living donor determines better recipient and graft survival (39).

Despite these benefits, up to 30% of patients with a possible willing living donor are not compatible with their donor, due to blood type incompatibility and previous sensitization against donor HLA (39). To overcome these limitations, different strategies have been developed as kidney paired donation (KPD). In KPD programs, an incompatible donor-recipient pair is matched with one or more pairs. In the simplest form, two incompatible pairs are matched to each other. More complex transplant chains involve a deceased transplant donor which can initiate a donation cluster. The organ is returned to the deceased donor waiting list patient at the end of the donation cluster (Figure 6). In this scenario, larger a database is needed to identify multiple pairs to increase potential transplant leading to a logistically challenging organization.

Under these circumstances, DLT could represent a great opportunity to create an international waitlist database to increase the chance of a KPD and to activate kidney donor chain (2). DLT decentralization could guarantee transparency, trustworthiness, and auditability by any node of the network (21).