Post-transplant lymphoproliferative disorder associated Epstein-Barr virus DNAemia after liver transplantation in children: Experience from single center.

The most prevalent malignancy that complicates both adult and pediatric solid organ transplantation is post-transplant lymphoproliferative disorder (PTLD). This study aimed to analyze the clinical and pathological characteristics, treatments, and outcomes of Epstein-Barr virus (EBV) DNAemia and PTLD in pediatric liver transplant recipients. A retrospective chart review was performed on 112 patients less than 18 years of age who underwent isolated orthotopic liver transplantation (OLT) between 2010 and 2022 at Ege University Children's Hospital. Data gathered for 1-year post-OLT included age at OLT, EBV, immunoglobulin (Ig)M/IgG status of the donor and recipient, indication for OLT, induction regimen, all immunosuppression levels, date and result of EBV polymerase chain reaction testing, rejection episodes documented by liver biopsy, and the development of PTLD. Forty-nine patients (43.75%) developed EBV DNAemia (median interval from surgery: 2 months, min-max: 2-36), of which 43 (87.8%) grafts came from living donors, and 6 (12.2%) came from deceased donors. Nine (18.4%) patients died during follow-up, and eight (16.3%) developed PTLD. Of these 8 patients; five patients developed EBV-related disease, one child developed hemophagocytic lymphohistiocytosis, one developed aplastic anemia, and one child developed B cell lymphoma. When PTLD patients and without-PTLD patients were compared, pediatric intensive care unit hospitalization, abnormal bone marrow biopsy findings, lymphadenopathy, age at diagnosis of EBV DNAemia, EBV viral load, tacrolimus (FK 506) pre-infection, were higher and tacrolimus 1-month levels were lower in patients with PTLD (p < 0.05). In logistic regression analysis, we showed that the age at diagnosis of EBV DNAemia was significantly higher in children with PTLD (p = 0.045; OR: 1.389; 95% CI: 1.007-1.914). PTLD is a rare but severe complication associated with EBV after OLT. This study demonstrated that PTLD is associated with older age, higher tacrolimus blood levels before EBV DNAemia, and higher peak EBV viral load at 1 month of EBV DNAemia.

T-Cell Posttransplant Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Systemic Review.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

Management of paediatric monomorphic post-transplant lymphoproliferative disorders with low-intensity treatment: A multicentre international experience.

BACKGROUND: Monomorphic post-transplant lymphoproliferative disorder (mPTLD) is a major cause of morbidity/mortality following solid organ transplant (SOT), with infection, mPTLD progression and organ rejection presenting equal risks. Balancing these risks is challenging, and the intensity of therapy required by individual patients is not defined. Although an increasing body of evidence supports the use of a stepwise escalation of therapy through reduction in immunosuppression (RIS) to rituximab monotherapy and low-dose chemo-immunotherapy, many centres still use B-cell non-Hodgkin lymphoma (B-NHL) protocols, especially when managing Burkitt/Burkitt-like (BL) PTLD. This study sought to define outcomes for children managed in the UK or Spanish centres using low-intensity first-line treatments. PROCEDURE: Retrospective data were anonymously collected on patients younger than 18 years of age, with post-SOT mPTLD diagnosed between 2000 and 2020. Only patients given low-intensity treatment at initial diagnosis were included. RESULTS: Fifty-six patients were identified. Age range was 0.9-18 years (median 10.7). Most (62.5%) had early-onset PTLD. Haematopathological analysis showed 75% were diffuse large B-cell like, 14.3% were BL and nine of 33 (27%) harboured a MYC-rearrangement. Stage III-IV disease was present in 78.6%. All but one had RIS, 26 received rituximab monotherapy and 24 low-dose chemo-immunotherapy, mostly R-COP. Intensified B-NHL chemotherapy was required in 10/56 (17.9%). There were a total of 13 deaths in this cohort, three related to PTLD progression. The 1-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 92.8%, 78.6% and 80.2%, respectively. CONCLUSIONS: R-COP provides an effective low-dose chemotherapy option. Escalation to more intensive therapies in the minority of inadequately controlled patients is an effective strategy.

[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

Epstein-Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada.

Epstein-Barr virus-related post-transplantation lymphoproliferative disorder (EBV-PTLD) is a serious complication following hematopoietic stem cell transplantation (HSCT). A pre-emptive strategy using rituximab, which aims to manage patients early at the time of EBV reactivation to avoid PTLD, has been recommended by the most recent ECIL-6 guidelines in 2016. However, there is still a great heterogeneity of viral-load monitoring protocols, targeted patient populations, and pre-emptive treatment characteristics between centers, making precise EBV monitoring recommendations difficult. We conducted a literature review from the most recent publications between 1 January 2015 and 1 August 2023, to summarize the emerging data on EBV-PTLD prevention strategies in HSCT recipients, including the EBV-DNA threshold and use of rituximab. We also present the results of a survey of current practices carried out in 12 of the main HSCT centers across Canada. We confirm that pre-emptive rituximab remains an efficient strategy for EBV-PTLD prevention. However, there is an urgent need to perform prospective, randomized, multicentric trials with larger numbers of patients reflecting current practices to determine the best clinical conduct with regards to rituximab dosing, timing of treatment, and criteria to initiate treatments. Longer follow-ups will also be necessary to assess patients' long-term outcomes.

Comparative analysis of tabelecleucel and current treatment in patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease following hematopoietic cell transplant or solid organ transplant.

AIMS: With recent European Union marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy approved for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). In the absence of a control arm, real-world evidence can provide a comparative benchmark for single-arm studies in ultra-rare populations. This study assessed the treatment effect of tabelecleucel in the single-arm phase 3 ALLELE study (NCT03394365) versus a treatment group from a multinational, multicenter retrospective chart review study (RS002) of patients with EBV+ PTLD. METHODS: In ALLELE, patients had disease relapsed/refractory to rituximab ± chemotherapy and received tabelecleucel 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Patients in RS002 had disease relapsed/refractory to rituximab ± chemotherapy and received next line of systemic therapy between January 2000 and December 2018. Propensity score-based standardized mortality/morbidity ratio weighting was used to achieve balance between treatment and comparator arms. Kaplan-Meier estimators and Cox regression models were used to compare overall survival (OS) in the re-weighted sample. RESULTS: 30 patients (n = 14 hematopoietic cell transplant [HCT], n = 16 solid organ transplant [SOT]) from ALLELE (data cutoff: November 2021) and 84 patients (n = 36 HCT, n = 48 SOT) from RS002 (data lock: January 2021) were included. Median time from diagnosis to first tabelecleucel dose (ALLELE) or start date of next line of systemic therapy (RS002) was 3.6 months. Tabelecleucel was associated with a substantial OS benefit compared with current treatment, with an unadjusted HR of 0.47 (95% confidence interval [CI] 0.25-0.88) and adjusted HR of 0.37 (95% CI 0.20-0.71) when using the start date of the next line of therapy as the index date. Sensitivity analyses yielded consistent results. CONCLUSIONS: In this study of real-world data, tabelecleucel was associated with an OS benefit among patients with R/R EBV+ PTLD for whom there is high unmet need.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

Pediatric Kidney Transplantation: Cancer and Cancer Risk.

Children with end-stage kidney disease (ESKD) face a lifetime of complex medical care, alternating between maintenance chronic dialysis and kidney transplantation. Kidney transplantation has emerged as the optimal treatment of ESKD for children and provides important quality of life and survival advantages. Although transplantation is the preferred therapy, lifetime exposure to immunosuppression among children with ESKD is associated with increased morbidity, including an increased risk of cancer. Following pediatric kidney transplantation, cancer events occurring during childhood or young adulthood can be divided into two broad categories: post-transplant lymphoproliferative disorders and non-lymphoproliferative solid tumors. This review provides an overview of cancer incidence, types, outcomes, and preventive strategies in this population.

Tabelecleucel for EBV+ PTLD after allogeneic HCT or SOT in a multicenter expanded access protocol.

ABSTRACT: Patients with Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disease (EBV+ PTLD) in whom initial treatment fails have few options and historically low median overall survival (OS) of 0.7 months after allogeneic hematopoietic cell transplant (HCT) and 4.1 months after solid organ transplant (SOT). Tabelecleucel is an off-the-shelf, allogeneic EBV-specific cytotoxic T-lymphocyte immunotherapy for EBV+ PTLD. Previous single-center experience showed responses in patients with EBV+ PTLD after HCT or SOT. We now report outcomes from a multicenter expanded access protocol in HCT (n = 14) and SOT (n = 12) recipients treated with tabelecleucel for EBV+ PTLD that was relapsed/refractory (R/R) to rituximab with/without chemotherapy. The investigator-assessed objective response rate was 65.4% overall (including 38.5% with a complete and 26.9% with a partial response), 50.0% in HCT, and 83.3% in SOT. The estimated 1- and 2-year OS rates were both 70.0% (95% confidence interval [CI], 46.5-84.7) overall, both 61.5% (95% CI, 30.8-81.8) in HCT, and both 81.5% (95% CI, 43.5-95.1) in SOT (median follow-up: 8.2, 2.8, and 22.5 months, respectively). Patients responding to tabelecleucel had higher 1- and 2-year OS rates (94.1%) than nonresponders (0%). Treatment was well tolerated, with no reports of tumor flare, cytokine release syndrome, or rejection of marrow and SOT. Results demonstrate clinically meaningful outcomes across a broad population treated with tabelecleucel, indicating a potentially transformative and accessible treatment advance for R/R EBV+ PTLD after HCT or SOT. This trial was registered at www.ClinicalTrials.gov as #NCT02822495.

Effect of pre-emptive rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients: A case series from the pediatric nephrology research consortium.

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States.

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

Epidemiology of Cancer in Kidney Transplant Recipients.

Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.

Post-Transplant Lymphoproliferative Disorders.

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogenous set of unregulated lymphoid cell proliferations after organ or tissue transplant. A majority of cases are associated with the Epstein-Barr virus and higher intensity of pharmacologic immunosuppression. The clinical presentations are numerous. The diagnosis is ideally by histology, except in cases where the tumor is inaccessible to biopsy. While some pre-emptive therapies and treatment strategies are available have reasonable success are available, they do not eliminate the high morbidity and significant mortality after PTLD.

Risk Factors Associated with PTLD Related Mortality in Adult Multivisceral Transplant Recipients - A Single Centre Cohort Study.

Background: PTLD is a heterogeneous group of lymphoproliferative diseases which can add significant mortality following multivisceral transplantation (MVTx). Our study aimed to identify potential risk factors of mortality in adult MVTx recipients who developed PTLD. Methods: All adult recipients of intestinal-containing grafts transplanted in our institution between 2013 and 2022, and who developed PTLD, were included in the study. Results: PTLD-associated mortality was 28.6% (6/21). Increased relative risk of mortality was associated with Stage 3 ECOG performance score (p=0.005; HR 34.77; 95%CI 2.94-410.91), if the recipients had a splenectomy (p=0.036; HR 14.36; 95%CI 1.19-172.89), or required retransplantation (p=0.039; HR 11.23; 95% CI 1.13-112.12). There was a significant trend for increased risk of PTLD mortality with higher peak EBV load (p=0.008), longer time from MVTx to PTLD diagnosis (p=0.008), and higher donor age (p 0.001). Peak LDH before treatment commencement was significantly higher in the mortality group vs the survival group (520.3 +- 422.8 IU/L vs 321.8 +- 154.4 IU/L; HR 1.00, 95%CI 1.00 to 1.01, p=0.019). Peak viral load prior to treatment initiation (Cycle Threshold (CT) cutoff = 32) correlated with the relative risk of death in MVTx patients who developed PTLD [29.4 (3.5) CTs in survivors compared to 23.0 (4.0) CTs in the mortality group]. Conclusions: This is the first study to identify risk factors for PTLD-associated mortality in an adult MVTx recipient cohort. Validation in larger multicentre studies and subsequent risk stratification according to these risk factors may contribute to better survival in this group of patients.

Epstein-Barr virus associated colitis in kidney transplant patients: a case series.

BACKGROUND: Gastrointestinal complications are common in kidney transplant (KT) patients and can be a consequence of the chronic use of immunosuppression. The differential diagnosis of colitis in KT patients includes intolerance to immunosuppressive agents, namely mycophenolate mofetil, de novo inflammatory bowel disease (IBD) and opportunistic infections. Epstein-Barr virus (EBV) infection may cause post-transplant colitis or trigger de novo IBD, although is seldom thought as the causative pathogen. OBJECTIVES: To describe clinical characteristics, endoscopic and histological findings, treatment and outcome of three patients that developed EBV associated colitis following kidney transplantation. METHODS: We retrospectively analyzed three patients with EBV associated colitis; clinical data including transplantation, gastrointestinal symptoms, endoscopy findings, and follow-up data was obtained. RESULTS: We present a case series of three patients with EBV colitis following KT, with an average age at clinical presentation of 59 years and elapsed time since the KT ranging from five to 22 years. Clinical manifestations included bloody diarrhoea, abdominal pain, weight loss and/or fever. Cytomegalovirus colitis, mycophenolate mofetil-related colitis, lymphoproliferative disease and graft versus host disease were excluded. One patient had a prior diagnosis of IBD. Two of the three patients had an unfavourable outcome with death despite reduction and/or switching of immunosuppressants, optimal medical treatment (including antiviral and intravenous immunoglobulin therapies) and salvage surgical therapy. CONCLUSION: A multidisciplinary approach is necessary to allow an expeditious diagnosis of a rare entity such as EBV associated colitis in KT. Long-term surveillance of these patients and the development of effective and safe therapies is essential.

Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation. A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes. Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.

Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.