【Objective and Design】 Antibody-mediated rejection (ABMR) is one of the major causes of kidney graft failure, but the efficacy and safety of treatment with rituximab remain unclear. We conducted an open-label, non-randomized, multicenter Phase III study to evaluate the efficacy and safety of rituximab for ABMR treatment.

【Methods】 Rituximab 375 mg/m² was administrated once or twice after steroid pulse therapy and optional plasma exchange in patients resulted in ABMR attributable to donor-specific antibodies (DSA) or anti-A/anti-B antibodies. Patients were aged 16 years or older and had a diagnosis of active or chronic active ABMR accompanied by worsening serum creatinine levels.

【Results】 Treatment was initiated immediately upon suspicion of ABMR, and 28 patients received rituximab. Efficacy was evaluated in 25 patients who were diagnosed with active (4 cases) or chronic active ABMR (21 cases) based on the Banff 2017 classification. The primary endpoint was the proportion of patients whose serum creatinine levels at 1 month after the rituximab administration (Day 1) showed improvement or remained stable, compared to the worst value during ABMR treatment to just before rituximab administration. In 19 out of 25 patients (76.0%, 95% confidence interval: 54.9; 90.6%), serum creatinine had improved or remained stable. There were no graft losses or patient deaths up to the final observation point, 6 months after the start of treatment. There were no serious adverse reactions related to rituximab.

【Conclusion】 Efficacy and tolerability were confirmed for rituximab after implementing steroid pulse therapy and optional plasma exchange for ABMR following kidney transplantation.

Liver transplantation is the standard therapy for end-stage liver disease, yet the persistent shortage of suitable donors remains a significant barrier. In response, various surgical innovations have been developed, including living donor liver transplantation (LDLT), particularly in Asia where social and cultural factors limit deceased donation. When a single living donor is unsuitable due to insufficient graft volume or hepatic steatosis, dual graft liver transplantation (DGLT) offers a viable alternative by utilizing two partial grafts from separate donors. Our institution initiated a dual graft living donor liver transplantation (DGLDLT) program in 2023. To date, we have performed three successful cases using two left-lobe grafts to prioritize donor safety. These experiences demonstrate that DGLT can be a feasible and effective approach, allowing the use of otherwise unsuitable donors while maintaining graft viability. Between 2013 and 2023, 144 patients were evaluated as suitable candidates for LDLT at our center, but 52 (36%) could not undergo transplantation due to donor limitations—mainly insufficient liver volume or fatty liver. This highlights the critical role of DGLT in expanding transplant eligibility in regions facing donor shortages. While DGLT requires meticulous planning and carries ethical considerations due to the involvement of two donors, our initial results support its utility and safety. Continued refinement and experience will be essential to further establish DGLT as a reliable option in living donor liver transplantation.

Since the Organ Transplantation Act was passed in October 1997, a total of 930 heart transplantations (HTx) have been performed in Japan as of December, 2024. After the Revised Transplant Act came into effect in July 2010, the number of brain-dead organ donation increased and 84 HTx were performed in 2019. In 2020 and 2021, the number of HTx decreased due to the COVID-19 pandemic. However, as the severity and mortality of COVID-19 decreased in 2022, the number of HTx increased, with over 110 HTx performed since 2023. After approval of the use of an implantable continuous-flow ventricular assist device (iVAD) for bridge-to-transplant (BTT) in 2011, BTT cases using iVAD increased. Currently, most patients are waiting for transplantation with VAD implantation.

Although the survival rate after HTx in Japan is favorable, the waiting period is extremely long. The relatively high rate of death while waiting for HTx is big problem, and the allocation system has been revised to allow more urgent patients to receive transplantation.

【Objective】 This paper presents the 21st official registry report on lung transplantation in Japan, conducted by the Japanese Society of Lung and Heart-Lung Transplantation since 2005.

【Design and Methods】 This report analyzes data from all lung transplant cases performed in Japan up to the end of 2024, including cadaveric lung transplantation, living-donor lung transplantation, and heart-lung transplantation. The data cover recipient numbers, underlying diseases, transplant procedures, postoperative survival rates, functional status, working status, and causes of death. Survival rates were calculated using the Kaplan-Meier method.

【Results】 In 2024, the number of newly registered candidates for lung transplantation surpassed 300 for the first time, reaching a record high of 304. Similarly, the number of lung transplants performed reached an all-time high of 148 cases. Among them, cadaveric lung transplants accounted for the majority, while the proportion of living-donor lung transplants continued to decline, representing only 12.2% (18 cases) in 2024. By the end of 2024, the cumulative number of lung transplants performed in Japan reached 1,315, comprising 505 single cadaveric lung transplants, 496 bilateral cadaveric lung transplants, 311 living-donor lung transplants, and 3 heart-lung transplants. As of that time, lung transplantation had been performed at 11 institutions nationwide. Regarding indications, idiopathic interstitial pneumonia (IIP) remained the most common indication for cadaveric single lung transplantation, while pulmonary hypertension continued to dominate in cadaveric bilateral cases. For living-donor lung transplantation, lung dysfunction after hematopoietic stem cell transplantation was the leading cause, and their proportion has been increasing year by year. The 5- and 10-year survival rates were 72.23% and 59.92%, respectively, for cadaveric lung transplantation, clearly exceeding international benchmarks for deceased donor lung transplantation reported by the International Thoracic Organ Transplant Registry (Europe: 57.3% and 38.8%; North America: 52.5% and 28.5%). The survival rates for living-donor lung transplantation were similarly favorable, with 5- and 10-year survival of 72.20% and 59.44%, respectively. All three recipients of heart-lung transplantation remain alive, with a 5-year survival rate of 100%. Assessment of postoperative functional status using the mMRC scale showed that 73.6% of cadaveric and 62.7% of living-donor lung transplant recipients achieved grade 0 or 1. Employment or active social participation was reported in 75.7% of cadaveric and 79.5% of living-donor recipients. Among 1,315 recipients, 272 deaths occurred in cadaveric lung transplant recipients and 119 in living-donor recipients. Infections were the most frequent cause of death in both groups (32.7% and 34.5%, respectively). Chronic lung allograft dysfunction (CLAD), malignancies, and post-transplant lymphoproliferative disorder (PTLD) have become increasingly prevalent causes of late mortality. In contrast, early deaths from primary graft dysfunction have decreased significantly, now accounting for only 5.5% (cadaveric) and 3.4% (living-donor) of all deaths.

【Conclusion】 The outcomes of lung transplantation in Japan remain favorable, with postoperative survival and functional outcomes continuing to exceed international benchmarks. Following a temporary decline in transplant numbers due to the COVID-19 pandemic in 2020, the program has steadily recovered and expanded, culminating in a record 148 transplants in 2024. The Japanese Society of Lung and Heart-Lung Transplantation will continue to compile and report annual registry data to ensure accurate monitoring and information sharing across institutions.

A total of 600 cases of pancreas transplantation from deceased and living-related donors were performed in 22 institutions in Japan between April 2000 and the end of 2024. The following donor- and recipient-related factors were analyzed in the 573 cases from deceased donors out of the total 600 cases: age and gender of donor and recipient, cause of death, history of diabetes and hemodialysis, waiting period, total cold ischemic time, operative procedure, immunosuppression and posttransplant survival rates of patient and graft. Based on the analyses, the current status of pancreas transplantation in Japan was described. The patient survival after the transplantation was 95.8%, 94.0% and 92.2% at 1, 3, and 5 years, respectively. The pancreas graft survival in cases with simultaneous pancreas and kidney transplantation (SPK) was 87.6%, 84.2%, and 81.7% at 1, 3, and 5 years, respectively. The pancreas graft survival in cases with pancreas after kidney transplantation (PAK) (82.7%, 68.1%, and 58.5% at 1, 3, and 5 years, respectively) and pancreas transplantation alone (PTA) (70.6%, 44.0%, and 29.3% at 1, 3, and 5 years) was significantly poorer than for SPK. The main cause of pancreas graft loss was graft thrombus in SPK cases, while it was chronic rejection in PAK and PTA cases. In conclusion, we summarized the current status of pancreas transplantation in Japan. While the posttransplant outcome was favorable, it is necessary to overcome graft thrombus in SPK cases and chronic rejection in PAK and PTA cases to improve the posttransplant outcomes.

In 2024, six islet transplants were performed in four patients. The majority of donors were in their 60s (three cases), followed by one each in their 30s, 40s, and 50s. All were male, brain-dead donors. Islet isolation and transplantations were performed at Fukuoka University Hospital (3 cases), the National Center for Global Health and Medicine (2 cases), and Fujita Health University Hospital (1 case). Warm ischemia time was 0 minutes in all cases, and the median cold ischemia time was 502 minutes. The median islet yield was 288,662.5 IEQ. All cases met the transplant criteria at each facility and were successfully transplanted.

Recipients included one patient in their 40s, one patient in their 60s, and two patients in their 70s. The patient at Fukuoka University Hospital was the first, second, and third islet transplant in 2024. All other cases were first-time transplants. No serious adverse events were observed, demonstrating the effectiveness of a minimally invasive and highly safe transplant procedure. Unfortunately, there have been no cases of insulin withdrawal, but the procedure is thought to contribute to blood sugar stability in type 1 diabetes patients.

Hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for a wide range of otherwise fatal hematologic disorders, and the number of HSCTs has continued to increase over the last 30 years; more than 5,500 allogeneic and autologous HSCTs have been performed annually in recent years. A constant increase of allogeneic HSCTs for older (aged over 50) patients, and an increase in the variety of donor/stem cell sources such as cord blood from unrelated donors, have led to this constant increase of HSCT in Japan. The transplant survival outcome also continues to improve and the assets for the improvement include better supportive care, innovative transplant approaches, and the considerable contribution of a well-established transplant outcome registry to a variety of clinical studies.