A2 Donor Lungs for O Recipient Transplant

Overseen by Shaf Keshavjee, MD MSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University Health Network, Toronto

Disqualifiers: Re-transplant, Multiorgan transplant, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 antibody titers and with the use of peri-operative antibody-depleting therapies. Since blood group O lung transplant candidates tend to have longer wait times and a higher waitlist mortality compared to other blood groups, we propose to conduct a prospective study of lung transplantation from blood group A2 donors to eligible blood group O recipients in an effort to increase the available donor pool. 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 on reducing transplant wait times among blood group O lung transplant candidates. This would represent the first prospective study of ABO-incompatible lung transplants worldwide.

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 data supports the idea that A2 Donor Lungs for O Recipient Transplant is an effective treatment?

The available research shows that using A2 donor lungs for O recipient transplants can be effective. One study describes a successful case where a patient with a different blood type received a lung transplant and was doing well nine months later. This suggests that even when blood types don't match perfectly, the treatment can still work. However, the research also highlights challenges for blood group O patients in getting transplants due to fewer available donors, which makes this treatment option important for them. ^{1 2 3 4 5}

What safety data exists for A2 donor lungs to O recipient transplants?

The available research does not directly address the safety of A2 donor lungs to O recipient transplants. However, related studies on ABO-incompatible transplants, such as A2-to-O liver transplants, suggest that these procedures can be successful with careful management of antibody-mediated rejection. A case of ABO-incompatible lung transplantation in a pediatric patient was successful, indicating potential for safety in similar lung transplant scenarios. ^{1 3 6 7 8}

Is the treatment of using A2 donor lungs for O recipient transplants promising?

Yes, using A2 donor lungs for O recipient transplants is promising because it can increase the number of available lungs for transplant, especially for blood group O patients who often have fewer options. Successful cases of ABO-incompatible lung transplants show that it can be a viable option, helping more patients receive the transplants they need. ^{1 3 8 9 10}

Research Team

Shaf Keshavjee, MD MSc

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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.

Low pre-operative anti-A antibody titers

Exclusion Criteria

I have received multiple organ transplants.

I am undergoing a second transplant.

Positive virtual crossmatch at time of transplant

Trial Timeline

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

Treatment Details

Interventions

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

Participant Groups

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+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Implications of blood group on lung transplantation rates: A propensity-matched registry analysis. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Intentional ABO-incompatible lung transplantation. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Lung transplant waitlist outcomes among ABO blood groups vary based on disease severity. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Successful management of an ABO-mismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Single-lung transplantation with ABO-compatible donors results in excellent outcomes. [2014]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of blood group A2-to-O liver transplantation: an analysis of the United Network of Organ Sharing database. [2012]

7. Denmark pubmed.ncbi.nlm.nih.gov

Plasmapheresis treatment of antibody-mediated rejection in an A2 donor to O pediatric liver transplant recipient. [2011]

8. United States pubmed.ncbi.nlm.nih.gov

ABO-incompatible living-donor lobar lung transplantation. [2011]

9. United States pubmed.ncbi.nlm.nih.gov

Relationship between anti-ABO antibody production and hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation. [2005]

10. Japan pubmed.ncbi.nlm.nih.gov

Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation. [2021]