Patient Information
This retrospective multicenter study includes nine patients in Japan who underwent single living-donor lobar lung transplantation (LDLLT) between November 2006 and December 2024. All patients had previously undergone hematopoietic stem cell transplantation (HSCT) from the same donor who subsequently provided lobar lung grafts for LDLLT. Patient demographics such as specific ages and genders are not reported in aggregate; however, all underwent transplantation at five Japanese centers. The main indication for lung transplantation was progressive pulmonary dysfunction or failure post-HSCT.
Diagnosis
Recipients typically presented with end-stage pulmonary disease necessitating lung transplantation after prior HSCT from the same donor. Diagnosis of respiratory failure was clinical, supplemented by imaging and pulmonary function assessments. The unique clinical scenario involved donor-cell chimerism from HSCT, which altered immunologic compatibility for the subsequent lung graft from the same donor.
Differential Diagnosis
In this immunologically complex scenario, clinicians would consider causes of lung failure including chronic graft-versus-host disease (GVHD)-related lung injury, infection, drug toxicity, and recurrence of primary disease. The differential also includes rejection types after transplantation, infection, and non-immune complications. These were evaluated and ruled out by standard clinical, radiologic, and laboratory criteria before transplantation.
Treatment and Management
All nine patients received single LDLLT grafts from the same donor as their prior HSCT. Post-transplant, all patients were initially treated with immunosuppressive therapy for at least three months. The immunosuppression regimens were individualized, emphasizing dose reduction tailored to the special immunologic context of donor-cell chimerism. Three patients were able to discontinue immunosuppression successfully during follow-up. The remaining six maintained reduced-dose immunosuppressive therapy adapted to their clinical status. Supportive care included nutritional support and monitoring for transplant-related complications.
Outcome and Prognosis
At a median follow-up of 154 months (~12.8 years), eight of nine patients were alive and maintained acceptable graft function, indicating excellent long-term transplant outcomes. One patient died 39 months post-LDLLT, with respiratory dysfunction presumed secondary to severe malnutrition rather than rejection or infection. This suggests good graft survival and manageable immunosuppression in this highly selected population.
Discussion
This case series addresses a rare but clinically important scenario: single LDLLT from the same donor as prior HSCT, leveraging donor-cell chimerism to potentially attenuate transplant rejection risk. The findings support that reduced or even discontinued immunosuppression is feasible in some recipients without compromising graft survival or function long-term. These observations align with the hypothesis that prior donor hematopoietic cell engraftment induces immune tolerance.
The study underscores the importance of individualized immunosuppression regimens in this unique setting, balancing rejection risk against immunosuppression complications. The long median follow-up and high survival rate advocate for the safety and efficacy of this approach under meticulous multidisciplinary management. Nutritional care emerged as a critical factor, given the mortality associated with malnutrition in this cohort.
These results enhance the understanding of immunologic mechanisms affecting lung transplantation outcomes in post-HSCT patients and may guide clinical decisions on immunosuppression minimization. This could reduce adverse effects and improve quality of life while maintaining graft function. Larger studies are needed to validate these findings and refine protocols.
References
1. Watanabe T et al. Immunosuppression and Long-term Survival After Single Living-donor Lobar Lung Transplantation From the Same Donor as Prior Hematopoietic Stem Cell Transplantation: An All-Japan Study. Transplantation. 2026 Oct 14. PMID: 42870335. Available from: https://pubmed.ncbi.nlm.nih.gov/42870335/
2. Chambers DC, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-seventh adult lung and heart-lung transplantation report—2020; Focus on deceased donor characteristics. J Heart Lung Transplant. 2020;39(10):1003-1016.
3. Kawai T, et al. Hematopoietic cell transplantation for tolerance induction: basic science to clinical application. Current Opinion in Organ Transplantation. 2014;19(4):434-440.
4. Palmer SM, et al. Lung transplantation for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation: case report and review of the literature. Transplantation. 1999;67(5):661-667.
5. Scully BM, et al. Managing immunosuppression after lung transplantation: a review of current practice and strategies. J Thorac Dis. 2019;11(Suppl 14):S1747-S1754.
| Summary of Patient Outcomes | Number of Patients (n=9) |
|---|---|
| Immunosuppression discontinued | 3 |
| Maintained reduced-dose immunosuppression | 6 |
| Alive at median 154 months follow-up | 8 |
| Deaths (cause: respiratory dysfunction linked to malnutrition) | 1 |
This case series offers valuable insights for transplant specialists, pulmonologists, and hematologists managing lung transplant recipients with prior HSCT. Understanding the immunologic interplay and potential for immunosuppression minimization may improve patient outcomes and long-term graft survival in this specialized group.
