A2 Donor Lungs for O Recipient Transplant

Overseen By Sharaniyaa Balachandran

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Re-transplant, Multiorgan transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist blood group O patients needing lung transplants. It examines using lungs from blood group A2 donors to reduce wait times and improve outcomes for blood group O patients. Known as blood group A2 donor to blood group O recipient lung transplant surgery, this approach has proven safe in kidney and liver transplants and is now being tested for lungs. Blood group O individuals needing their first lung transplant and having low levels of certain antibodies might be suitable for this study. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance transplant options for future patients.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that this lung transplant method is safe for recipients?

Research has shown that transplants between different blood types, such as from blood group A2 to blood group O, have succeeded in organs like the kidney and liver. With certain precautions, it can be safe to transplant organs from a donor with a different blood type.

For lung transplants, this method could save very sick patients who might otherwise wait too long for a suitable donor. However, lungs are more prone to rejection, so careful monitoring and treatment are necessary to address any issues.

Although detailed safety information specifically for A2 to O lung transplants is limited, the success in other organs provides some confidence in its potential safety. If the trial is in its early stages, initial results may be promising, but more research is needed to fully understand and confirm the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using A2 donor lungs for O recipient transplants because this approach could significantly expand the donor pool for patients with blood group O, who often face longer wait times for suitable organs. Traditionally, lung transplants require a perfect blood type match to avoid rejection. However, A2 blood group lungs have fewer A antigens, which might not trigger strong immune responses in O recipients, potentially reducing the risk of rejection. This method could lead to more timely transplants and improve survival rates for those with blood group O.

What evidence suggests that this A2 to O lung transplant is effective for reducing wait times?

Research has shown that using lungs from blood group A2 donors for patients with blood group O, as studied in this trial, could increase the number of available lungs for transplants. Studies on other organs, such as kidneys and livers, have found that A2 to O transplants are safe and successful, especially when combined with treatments that lower antibodies (proteins in the blood that attack foreign substances). Successful lung transplants between mismatched blood types have also occurred in both infants and adults, indicating this method can work in certain situations. This approach might help reduce wait times for blood group O patients, who usually wait longer for lung transplants. Overall, early evidence suggests this could be a promising way to help more people receive the transplants they need. ^{1 3 4 6 7}

Who Is on the Research Team?

Shaf Keshavjee, MD MSc

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for individuals who need their first lung transplant, have blood group O, and low levels of anti-A antibodies before surgery. They must consent to participate in the study. People needing a re-transplant or multiple organ transplants, or those with positive virtual crossmatch at the time of transplant cannot join.

Inclusion Criteria

I have had one lung transplant.

My blood type is O.

I agree to participate in the study.

Exclusion Criteria

I have received multiple organ transplants.

I am undergoing a second transplant.

Positive virtual crossmatch at time of transplant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo lung transplantation from blood group A2 donors to blood group O recipients

1 week

Peri-operative care

Participants receive peri-operative antibody-depleting therapies to ensure transplant compatibility

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after transplantation

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Blood group A2 donor to blood group O recipient lung transplant surgery

Trial Overview The study is testing if lung transplants from donors with blood group A2 to recipients with blood group O are safe and can help reduce waiting times for these patients. It's the first worldwide prospective study on this type of ABO-incompatible lung transplant.

How Is the Trial Designed?

Group I: A2 donor transplant to O recipient Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

A successful lung transplant was performed on a blood group O cystic fibrosis patient using a blood group AB donor lung, despite the incompatibility, by employing a comprehensive antibody depletion protocol.

Nine months post-transplant, the patient is doing well at home, demonstrating the potential for successful outcomes in high-risk transplant scenarios with careful management of blood group incompatibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intentional ABO-incompatible lung transplantation. Strüber, M., Warnecke, G., Hafer, C., et al.[2023]

A study of 43,335 O blood type recipients showed that A2-to-O liver transplantation is a safe option, with no significant differences in overall survival (77% for A2 vs. 74% for O) or graft survival (66% for both groups) at 5 years.

Despite A2 recipients being more likely to be hospitalized and having higher liver disease scores at transplantation, there were no significant differences in rejection rates or causes of graft failure, indicating that A2 grafts can effectively meet the needs of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of blood group A2-to-O liver transplantation: an analysis of the United Network of Organ Sharing database. Kluger, MD., Guarrera, JV., Olsen, SK., et al.[2012]

Kidneys from A2 blood group donors can be safely transplanted into O blood group recipients with low levels of anti-A antibodies, indicating a potential for broader donor-recipient compatibility in kidney transplants.

In a rare case, a pediatric O blood group recipient of an A2 donor liver experienced combined cell and antibody-mediated rejection, which was successfully treated using plasmapheresis (PP) and intravenous immunoglobulin (IVIG), highlighting the need for careful monitoring in liver transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasmapheresis treatment of antibody-mediated rejection in an A2 donor to O pediatric liver transplant recipient. Martin, T., Schwartz, J., Demetris, A., et al.[2011]

In a study of 32,772 lung transplant waitlist candidates, blood group O showed a 20% lower transplantation rate and a higher risk of waitlist death/removal in the lowest lung allocation score (LAS) quartile compared to blood group A.

Conversely, blood group AB had a 52% higher transplantation rate in the lowest LAS quartile, while groups B and AB experienced reduced transplantation rates and increased waitlist death/removal in the highest LAS quartile, indicating that waitlist outcomes vary significantly by blood type and disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung transplant waitlist outcomes among ABO blood groups vary based on disease severity. Greissman, S., Anderson, M., Dimango, A., et al.[2023]

In a study of 28 patients who underwent living donor lobar lung transplantation (LDLLT), 46.4% received lungs from minor ABO-mismatched donors, and all patients survived with a mean follow-up of 28 months, indicating the safety and viability of this approach.

Although anti-ABO antibodies were detected in 38.5% of patients with mismatched transplants, only one patient experienced severe hemolytic anemia, suggesting that LDLLT across ABO mismatches can be performed with careful monitoring and is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between anti-ABO antibody production and hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation. Sano, Y., Date, H., Nagahiro, I., et al.[2005]

Type O candidates for lung transplantation have lower rates of receiving transplants (73.1%) compared to non-O candidates (77.0%), indicating a potential bias in the allocation process.

Additionally, type O candidates face higher waiting list mortality rates (12.5%) compared to non-O candidates (10.1%), suggesting that changes in organ allocation policies may be needed to improve equity in access to lung transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of blood group on lung transplantation rates: A propensity-matched registry analysis. Barac, YD., Mulvihill, MS., Cox, ML., et al.[2020]

A 67-year-old patient with blood type B successfully received a lung transplant from a blood type A donor, demonstrating that ABO-mismatched lung allografts can be managed effectively.

The use of immunosuppressive therapies, including cyclophosphamide and antigen-specific immunoadsorption, successfully reduced harmful anti-A antibody levels, preserved graft function, and resulted in a favorable clinical outcome three years post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful management of an ABO-mismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy. Pierson, RN., Loyd, JE., Goodwin, A., et al.[2021]

A study of 3,572 single-lung transplants found that using ABO-compatible donors resulted in similar survival rates compared to ABO-identical donors, indicating that ABO compatibility does not negatively impact transplant outcomes.

Carefully selected ABO-compatible donors led to excellent post-transplant results, with no significant differences in mortality or lung function between the two donor types, suggesting that ABO compatibility can be a viable option in lung transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-lung transplantation with ABO-compatible donors results in excellent outcomes. Taghavi, S., Jayarajan, SN., Furuya, Y., et al.[2014]

In a study of 23 patients who underwent living-donor lobar lung transplantation (LDLLT), none developed clinical signs of hemolytic anemia, indicating that the procedure is safe even with minor ABO mismatches.

Among the 11 patients with minor ABO mismatches, only 2 showed a transient increase in anti-B antibodies, which did not lead to significant complications, suggesting that LDLLT can be effectively performed with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation. Ohsumi, A., Chen, F., Yurugi, K., et al.[2021]

This case marks the first successful living-donor lobar lung transplantation from ABO-incompatible donors, demonstrating a new possibility for lung transplants in patients with blood type changes after treatments like bone marrow transplantation.

The 10-year-old boy, who had previously undergone bone marrow transplantation for acute myeloid leukemia, received lungs from type B and AB donors without any anti-A/B antibodies, indicating a safe and effective approach to transplantation despite blood type incompatibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABO-incompatible living-donor lobar lung transplantation. Shoji, T., Bando, T., Fujinaga, T., et al.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10323570/

ABO blood type incompatible lung transplantation - PMC ABO-incompatible lung transplantation might be a viable method to save critically ill patients with end-stage respiratory diseases.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05581745/a2-to-o-lung-transplants

A2 to O Lung Transplants | Clinical Research Trial Listing Blood group A2 to blood group O kidney and liver transplants have been shown to be safe and successful, especially in recipients with low pre-operative anti-A ...

3. jhltonline.org jhltonline.org/article/S1053-2498(24)01561-4/fulltext

ABO-incompatible heart transplantation—evolution of a ... Eight of 10 children survived 1 year after ABOi transplant with survival and freedom from rejection comparable to 10 ABO-compatible (ABOc) ...

4. researchgate.net researchgate.net/publication/372016342_ABO_blood_type_incompatible_lung_transplantation

(PDF) ABO blood type incompatible lung transplantation One infant and one adult had successful intentional major ABO-incompatible lung transplantation with both induction therapy and aggressive ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1053249824015614

ABO-incompatible heart transplantation—evolution of a ... Eight of 10 children survived 1 year after ABOi transplant with survival and freedom from rejection comparable to 10 ABO-compatible (ABOc) recipients up to 4.6 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05581745

Study Details | NCT05581745 | A2 to O Lung Transplants The aim of this study is to determine both the feasibility and safety of this specific type of ABO-incompatible lung transplant, and the impact of this practice ...

7. jtd.amegroups.org jtd.amegroups.org/article/view/10.21037/jtd-23-48/prf

ABO blood type incompatible lung transplantation ... data), and in particular comment on the increased wait list mortality for blood type O lung transplant candidates, in whom ABOi transplants may benefit the most ...