Hodgkin's lymphoma after post-transplant lymphoproliferative disease in a renal transplant recipient

Lymphoid malignancies such as post-transplant lymphoproliferative disease (PTLD) are a major complication of solid organ transplantation. Hodgkin's lymphoma (HL) is not part of the typical spectrum of PTLD, but has rarely been reported as a separate complication. We report a case of HL occurring after previous PTLD in a renal transplant recipient. A 9-yr-old girl with end-stage autosomal recessive polycystic kidney disease received a cadaveric renal transplant at 1 yr of age. She developed polymorphic PTLD localized to the bone marrow at 6 yr post-transplant. She was treated with reduction of immunosuppression and alpha-interferon. No chemotherapy or anti-B cell antibody was administered. The PTLD resolved and kidney graft function remained stable. At 9 yr post-transplant, she presented again with fever of 2 wk duration, associated with enlarged lymph nodes at multiple sites. A lymph node biopsy revealed the presence of classic Reed Sternberg cells positive for CD15, CD30 and EB RNA. She was treated with standard combination chemotherapy for HL with COPP/ABV. All immunosuppressive agents were discontinued except for low dose prednisone. The patient had an excellent response, with resolution of her lymphadenopathy and maintenance of stable graft function. RS like cells have been reported in the setting of PTLD, but these cells possess an activated B cell phenotype, are EBV negative and CD15 negative. True HL following PTLD has been reported in only three previous cases, with good response to standard chemotherapy in each.     

Asymptomatic small bowel intussusception associated with post-transplant lymphoproliferative disease

Abstract:  A 2-yr-old boy who had undergone orthotopic liver transplantation for biliary atresia 6 months prior presented with generalized lymphadenopathy. Physical exam revealed lymphadenopathy only; the patient had no gastrointestinal signs or symptoms. CT was used to evaluate the patient's lymphadenopathy. The findings were consistent with PTLD, and an incidental intussusception causing small bowel obstruction was found. The intussusception was successfully managed expectantly, and the patient's PTLD responded to administration of rituximab. The etiology, diagnosis and management of intussusception is discussed.     

Epstein-Barr virus and post-transplant lymphoproliferative disease

There is convincing evidence that Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD). Primary EBV infection following transplantation occurs in as many as 90% of cases of PTLD in children and pretransplant EBV seronegativity is a recognized risk factor for developing PTLD. Other risk factors include young age at the time of transplant, the type of transplant that the recipient receives and the type and intensity of immunosuppression. The clinical presentation is often nonspecific and tissue biopsy is necessary to establish the diagnosis. There appears to be a correlation between PTLD and EBV viral load measured by polymerase chain reaction (PCR) of the peripheral blood and quantitative PCR may be a useful guide in the management of PTLD. Antiviral drugs and cytomegalovirus-immunoglobulin G may have a role in preventing PTLD. Because PTLD results from functional over-immunosuppression, the initial treatment is reduction of immunosuppression. Antiviral agents, interferon, immuno-based monoclonal therapy, cell-based therapy and chemotherapy also have a potential role in treating this disorder. At the present time there is no standardized approach to the evaluation and treatment of PTLD.     

Rapid response to rituximab in a pediatric liver transplant recipient with post-transplant lymphoproliferative disease and maintenance with sirolimus monotherapy

A 12-yr-old girl with end-stage renal disease secondary to primary hyperoxaluria type I received a living related (left lateral segment) liver transplant from her brother as the first step of a staged liver and kidney transplant. Renal transplantation was planned for a later date from the same donor. Nine weeks after transplantation she developed polymorphic PTLD of the tonsils and adenoids. Initial treatment with surgical resection and withdrawal of immunosuppression was insufficient as she developed recurrence of the PTLD lesion 1 wk after surgical resection and reduction of immunsuppression. Treatment with the chimeric monoclonal anti CD20 antibody, rituximab (Mabthera, Hoffman-La Roche AG, Grenzach-Whylen, Germany), resulted in quick response and complete recovery from PTLD within 2 wk, with no recurrence up to 8 months after treatment. Rejection prophylaxis was successfully achieved with Sirolimus (Rapamune, Wyeth Pharmaceuticals Inc., Philadelphia, PA, USA) monotherapy, with no episodes of acute rejection.     

Complete immunosuppressive withdrawal as a uniform approach to post-transplant lymphoproliferative disease in pediatric liver transplantation

Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients is associated with a high mortality (up to 60%) and the younger age groups, who are predominantly EBV‐naïve, are at highest risk for development of this disease. The aim of this study is to assess, in this high‐risk group, patient outcome and graft loss to rejection when complete withdrawal of immunosuppressive agents (IMS) is instituted as the mainstay of treatment in addition to the use of standard therapy. A retrospective analysis of 335 pediatric patients whose liver transplants were performed by our team between September 1988 and September 2002, was carried out through review of computer records, database and patient charts. Fifty patients developed either EBV or PTLD; 80% were ≤2 yr of age. Of these 50 patients, 19 had a positive tissue diagnosis for PTLD and 31 were diagnosed with EBV infection, 14 of whom had positive tissue for EBV. Fifty‐eight percent of patients who developed PTLD and 51.6% of patients with EBV received antibody for induction or treatment of rejection prior to onset of disease. Forty‐six patients (92%) received post‐transplant antiviral prophylaxis with ganciclovir or acyclovir. Antiviral treatment included ganciclovir in 76%, acyclovir in 20% and Cytogam (in addition to one of the former agents) in 44%. In those with PTLD, treatment included chemotherapy (n = 1), Rituximab (n = 2), and ocular radiation (n = 1). IMS was stopped in all patients with PTLD and in 19 with EBV infection and was held as long as there was no allograft rejection. Eight patients have remained off IMS for a mean of 1535.5 ± 623 days. Of the 21 patients who were restarted on IMS for acute rejection, 18 responded to steroids and/or reinstitution of low‐dose calcineurin inhibitors. The mean time to rejection while off IMS in this group was 107.43 ± 140 days (range: 7–476). Two patients were re‐transplanted for chronic rejection; one had chronic rejection that existed prior to discontinuing IMS. The mortality rate in our series was 31.6% in those with PTLD and 6% in those with EBV disease. The cause of death was related to PTLD or sepsis in all cases; no deaths were due to graft loss from acute or chronic rejection. PTLD is associated with high mortality in the pediatric population. Based on this report, we advocate aggressive management of PTLD that is composed of early cessation of IMS, the use of antiviral therapy, and chemotherapy when indicated. Episodes of rejection that occur after stopping IMS can be successfully treated with standard therapy without graft loss to acute rejection.     

Primary tacrolimus (FK506) therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients

While the overall incidence of post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients has been reported to be 4-11%, the long-term risk of PTLD associated with primary tacrolimus therapy is unknown. Therefore, in order to determine the incidence and long-term risk of PTLD, the present study examined 131 pediatric recipients who underwent liver transplantation (LTx) between October 1989 and December 1991 and received primary tacrolimus therapy. This cohort of children was evaluated over an extended time-period (until December 31 1996) with a mean follow-up of 6.3 yr. Actuarial Kaplan-Meier analysis was utilized to determine the risk of PTLD over time. The overall incidence of PTLD was 13% (17/131) with an average age of 4.3 +/- 0.75 yr at diagnosis. Pretransplant Epstein-Barr virus (EBV) serologies were negative in 82%, positive in 12%, and not available in 6% of the patients. The median time to diagnosis of PTLD post-Tx was 11.9 months (mean 16.4 +/- 3.9, range 1.7-63.0 months). Mean tacrolimus dose and plasma trough level (as evaluated by enzyme-linked immunosorbent assay [ELISA]) at the time of diagnosis was 0.32 +/- 0.06 mg/kg/day and 1.3 +/- 0.3 ng/mL, respectively. The cumulative long-term risk of PTLD was found to increase over time: 3% at 6 months, 8% at 1 yr, 12% at 2 yr, 14% at 3 yr, and 15% at 4 and 5 yr. Mortality from PTLD was 12% (two of 17 patients). Primary tacrolimus use in pediatric LTx has a long-term risk of PTLD approaching 15%, with the majority of episodes (78%) occurring in the first 2 yr, suggesting that intense EBV surveillance should occur early post-transplantation.     

Risk factors for post-transplant lymphoproliferative disorder in pediatric patients: a case-control study

Post-transplant Lymphoproliferative Disorder (PTLD) because of the Epstein-Barr Virus (EBV) is a major concern after pediatric transplantation. The group at greatest risk is EBV-seronegative recipients who receive EBV-seropositive organs. Additional risk factors remain to be determined, including those among EBV-seropositive recipients. In this case-control study, PTLD cases were biopsy-proven over a period of 4 yr (1997-2000, inclusive). Each case was matched with 2 controls, based on the type of organ transplanted and the period of transplantation (+/-1 yr). Variables compared between cases and controls included those relating to the clinical and virologic profiles and immunosuppressive therapy. Twenty-two cases of PTLD were diagnosed during the study period. PTLD cases occurred at a median of 22.8 months post-transplantation (range 1-131). The median age of cases was 26.2 months (range 6.1-194) compared with 47.4 months (range 0.8-202.2) for controls (p = 0.93). Cases had a higher mean baseline EBV load compared with controls (3.1 log(10) (s.d. +/- 1.0) vs. 1.6 log(10)/10(6) PBMCs (s.d. +/- 1.4), with every 1 log increase in viral load resulting in a three times increase in the likelihood of PTLD (p < 0.007). Close to one in four cases of PTLD were EBV-seropositive pretransplantation. These seropositive recipients tended to be older patients with a trend to a worse outcome compared with their seronegative counterparts. The occurrence of PTLD was not associated with the use of any specific immunosuppressants. A significant proportion of PTLD cases occurred among EBV-seropositive transplant recipients, with a tendency towards an unfavorable outcome. Besides EBV-seronegative recipients who receive seropositive organs, some EBV-seropositive pediatric patients are at risk of PTLD. Additional studies are warranted to further define the factors associated with PTLD in EBV-seropositive transplant recipients.     

Native kidney post-transplant lymphoproliferative disorder in a non-renal transplant patient

Abstract:  PTLD is an important post-transplant complication. Although PTLD affects kidney allografts after renal transplantation, it has not been reported in native kidneys of other solid organ recipients. Herein, we report a child who underwent an orthotropic liver transplant for cryptogenic cholestatic hepatitis and developed fever, generalized lymphadenopathy, chronic EBV viremia, and lymphatic PTLD. Subsequently, she also developed gross hematuria and nephrotic range proteinuria. Kidney histology revealed EBV-positive mononuclear infiltrates within the renal parenchyma consistent with PTLD. Electron microscopy examination demonstrated subepithelial electron-dense deposits consistent with a membranous glomerulopathy pattern. The PTLD was successfully treated with reduced immunosuppression and cyclic cyclophosphamide, rituximab, and prednisone, but the renal disease progressed to end-stage renal failure within two yr. Repeat kidney histology showed chronic nephropathy and membranous glomerulopathy without PTLD infiltrates or detectable EBV staining, although chronic viremia persisted. To our knowledge, this is the first such child to be reported and highlights the importance of remaining vigilant for renal PTLD even in non-kidney organ recipients.     

Severe cold agglutinin disease caused by recurrent monomorphic Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD), clonally related to an EBV-negative plasmacytic hyperplasia in a pediatric multivisceral organ transplant recipient

PTLD represent major post-transplant complications. The major etiologic factor is EBV. Association with cold agglutinin disease has not been described so far. We report a three-yr-old girl who developed oligoclonal EBV-negative plasmacytic hyperplasia as well as Coombs test-positive anemia one yr after multivisceral organ transplantation, performed after subtotal bowel resection for colointestinal aganglionosis and liver cirrhosis resulting from long-term parenteral nutrition. The patient was treated for plasmacytic hyperplasia with cyclophosphamide and prednisolone and achieved clinical remission. One yr later PTLD progressed possibly driven by EBV to DLBCL. The migration patterns of the amplified Ig heavy chain genes demonstrated a probable clonal relationship of the DLBCL to a clone almost present in the plasmacytic hyperplasia. This progression was accompanied by a rapid rise of cold agglutinin titers with symptoms of severe cold agglutinin disease, leading to right femoral and extern iliac vein thromboses requiring partial leg amputation. After four cycles of rituximab, cyclophosphamide, and prednisolone, the patient achieved complete PTLD remission and the cold agglutinins disappeared. Summarizing, PTLD may be accompanied by cold agglutinin disease, and both may be successfully treated by immuno-chemotherapy. The appearance of cold agglutinins in transplant patients may indicate PTLD development.     

Post-transplant lymphoproliferative disease in children

Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.     

Epstein–Barr virus-related post-transplant lymphoproliferative disease in solid organ transplant recipients, 1988–97: A Canadian multi-centre experience

The aim of this work was to obtain information on the magnitude of the problem, disease characteristics, and clinical practices relating to post-transplant lymphoproliferative disease (PTLD) in Canadian institutions. Adult and pediatric Canadian solid organ transplant groups were sent a questionnaire between July and October 1998. Analyzable data were obtained from 33 transplant groups. For the period 1988-97, 90 cases of PTLD were seen among 4283 solid organ transplant recipients. The incidence of PTLD varied from 0 to 14.6%, with the highest rates in children. Lymph nodes were the sites most frequently affected. Among the classifiable lesions, the majority were monoclonal. The lesions were of B-cell origin in 42.2% and of T-cell in 15.6%. The lesions were classified as monomorphic in 31.1%, polymorphic 18.9%, and hyperplastic in 1.1%. Tumors were reported as low grade in 26.7% and high grade in 10%. The majority of patients (71.1%) received reduced immunosuppression. Anti-viral agents were used in 52.2%. Chemotherapy was used in 27.8%, while immune globulin was used in 22.2%. Surgical resection was used in 20.0%, radiotherapy in 14.4%, and interferon-alpha therapy in 12.2%. The results showed that 48.9% of the patients had died, while 25.6% and 8.9% were regarded as having complete remission and partial remission, respectively. In conclusion, the incidence of PTLD varies widely across Canadian centres. Children are disproportionately affected and the mortality rate is high. Management practices vary significantly, and the need for information sharing was identified as one way of optimizing management.     

Sinusoidal CD30+ diffuse large B‐cell lymphoma can masquerade as anaplastic large cell lymphoma in pediatric posttransplant lymphoproliferative disorders

Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. Diffuse large B‐cell lymphoma (DLBCL) is frequently seen in this setting. However, CD30+ DLBCL with sinusoidal pattern of involvement has not been reported in pediatric PTLD. We are reporting a 9‐year‐old female child presented with diffuse lymphadenopathy postheart transplantation. The pattern of involvement was suggestive of anaplastic large cell lymphoma, but the malignant cells were positive for B‐cell markers and negative for anaplastic lymphoma kinase. The patient was treated aggressively with multiagent chemotherapy and rituximab. Accurate diagnosis in PTLD is paramount in making management decisions.     

EBV-negative lymphoproliferative disease with hyper-IgA, in a child with combined liver and small bowel transplantation

A 4-year-old boy presented 14 months after liver and small bowel transplantation with fever, diarrhea, elevated liver enzymes, thrombocytopenia and autoantibodies. Total gammaglobulins level was normal but the level of plasma IgA1 was very high. The blood PCR for Epstein-Barr virus (EBV) was negative. The ileal biopsy disclosed a lymphoplasmacytic infiltration. The EBER probe was negative on the small bowel biopsies. The child was considered as suffering from a non-EBV-induced posttransplant lymphoproliferative disorder (PTLD). The high IgA level was presumed to be secreted by proliferating plasma cells in the transplanted bowel. Immunosuppression was reduced; but the efficacy was incomplete and an anti-CD20 antibody was added. There was complete resolution of symptoms and normalization of the IgA level. As IgA1 is mostly of intestinal origin, this unusual presentation of PTLD should lead to a high suspicion of a small bowel proliferating process.     

Recombinant growth hormone use pretransplant and risk for post-transplant lymphoproliferative disease--a report of the NAPRTCS

Abstract:  rhGH, widely used to optimize linear growth in children with ESRD, also modulates B-cell precursor development and may be associated with malignancy development. To determine if rhGH use in children was associated with higher risk of PTLD, we analyzed retrospectively collected data on children with CRI, on dialysis or with renal transplants in a large multi-center registry of children with ESRD. Of the 194 LPD patients currently listed in the registry, 41 were previously enrolled in the CRI registry and 18/41 (43.9%) used rhGH during their period with CRI. Among CRI patients who later received a transplant, rates of PTLD post-transplant were significantly higher among rhGH users (18/407 or 4.4%) compared to patients who never used rhGH during their CRI follow-up and received a transplant (23/1240 or 1.9%, p = 0.009). After adjusting for the confounders of recipient age (at CRI and at transplant) and transplant era, the use of rhGH pretransplant was associated with a borderline higher risk for PTLD (odds ratio 1.88, 95% CI = 1.00–3.55, p = 0.05). In contrast, use of rhGH during dialysis or post-transplant only was not associated with a higher risk for PTLD. Continued monitoring is recommended.     

Report on the X-linked lymphoproliferative disease in an Australian family

X-linked lymphoproliferative disease is characterized by immune deficiency, particularly to the Epstein-Barr virus and by a tendency to develop fatal infectious mononucleosis, acquired hypogammaglobulinaemia or malignant lymphoma. This disorder has been diagnosed in three boys, two brothers and a maternally related cousin, residing in Australia. The proband presented at 6 years of age with fulminating infectious mononucleosis. His 9 year old male cousin had developed an ileal Burkitt lymphoma one year earlier. Immunological and molecular genetic evidence is presented to support our view that his younger sibling is also affected with this condition. DNA linkage studies using probes to DXS10 and DXS37 provide confirmatory evidence for the diagnosis in the proband's brother and information on carrier status in female family members.     

Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease

In contrast to solid organ transplantation (Tx), the incidence of post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell Tx (HSCT) is generally low. This risk, however, is significantly elevated in patients receiving human leukocyte antigen (HLA) mis-matched or T-cell-depleted grafts, or after treatment for severe graft-versus-host disease (GvHD). An 18-yr-old patient with positive Epstein-Barr virus (EBV) serology received a fully matched, unmanipulated bone marrow graft from an unrelated EBV-positive donor for treatment of acute myeloid leukemia (AML) in second complete remission. GvHD prophylaxis was performed with cyclosporin A (CsA) and a short course of methotrexate. Four months after Tx, the patient developed ulcerative tonsillitis that was unresponsive to antibiotic treatment. Diarrhea appearing simultaneously was interpreted as gastrointestinal GvHD and steroids were added to CsA. A few days later the patient was admitted to hospital because of generalized seizure and pneumonia. Despite reduction of immunosuppression, intensification of anti-viral treatment, and subsequent mechanical ventilation, the patient died of acute respiratory distress 6 days later. Autopsy demonstrated disseminated EBV-induced, multi-nodular lymphoma infiltration of the entire colon but no signs of GvHD. Moreover, both lungs, paratracheal lymph nodes, kidneys, thyroid gland, and liver were infiltrated with large B-cell non-Hodgkin's lymphomas. This case underlines the rapid and aggressive course of EBV-induced disseminated PTLD after HSCT, initially mimicking intestinal GvHD because of massive colonic lymphoma infiltration. Tissue biopsies should be performed early for establishing correct diagnosis, thus enabling specific therapy, e.g. infusion of donor leukocytes with cytotoxic T-lymphocytes.     

Chronic high Epstein-Barr viral load carriage in pediatric liver transplant recipients

Abstract:  Development of EBV disease and PTLD is usually accompanied by the detection of a high EBV load in peripheral blood. However, many children undergoing primary EBV infection following LTx will maintain chronically elevated EBV loads in the absence of clinical symptoms. To better understand this phenomenon, we retrospectively reviewed the records of children undergoing LTx at our center from 1997 to 2007 to identify chronic high EBV load carriers in this population. A CHL state was defined by the presence of a high load for >50% of samples for greater than or equal to six months following either asymptomatic or complete clinical resolution of EBV disease/PTLD. A total of 35 CHL carriers were identified. Pretransplant serologies were available for 29 of the 35; 22/29 (76%) were EBV negative prior to LTx; eight of these 22 developed their CHL state at the time of their primary EBV infection. Fourteen of the 35 had EBV disease (n = 7) or PTLD (n = 7) prior to development of the CHL state. Only one of 35 CHL carriers developed PTLD or lymphoma while they were a high load carrier. In all, 23/35 resolved their CHL state without apparent sequelae while 11 children continue to be asymptomatic high load carriers. These data provide important information about the outcome of chronic EBV high load carriage in pediatric liver transplant recipients.     

Post-transplant lymphoproliferative disease in pediatric lung transplant recipients: Recent advances in monitoring

Abstract: To investigate the clinical validity of newer diagnostic tests such as monitoring of EBVqPCR and lymphocyte function assay ImmuKnow in helping to diagnose PTLD in pediatric lung transplant recipients. Single‐center, retrospective case–control study. CsA trough levels, EBVqPCR and ImmuKnow (Cyclex Inc., Columbia, MD, USA) levels were measured serially as part of routine care. Re‐transplant patients and patients who did not reach 12 months post‐transplant at the time of analysis were excluded. Twenty‐seven patients met the inclusion criteria. The study group consisted of seven patients who developed PTLD, five of which were EBV? recipients who received EBV+ lungs. The rest of the eligible patients served as controls. Median time to develop PTLD was 273 days (range: 166–343). One, two, three, six, and nine months after transplant, mean (±s.d.) CsA trough whole blood levels (ng/mL) were not different between the two groups: 378 ± 38, 390 ± 52, 402 ± 89, 359 ± 42, and 342 ± 115, vs. 416 ± 105, 347 ± 64, 337 ± 78, 333 ± 86, and 281 ± 54 [PTLD vs. no‐PTLD, respectively (p > 0.05 for all time points)]. Mean (±s.d.) EBVqPCR levels (copies/mL) measured at three, six, and nine months post‐transplant were significantly elevated in PTLD group compared to no‐PTLD group: 84 ± 99, 3384 ± 7428 and 839 ± 1444 vs. 9 ± 26, 8 ± 36 and 32 ± 136, respectively (p < 0.05 for all time points). Mean (±s.d.) ImmuKnow levels (ATP ng/mL) at three, six, and nine months post‐transplant were significantly lower in the PTLD group when compared with no‐PTLD group: 144 ± 67, 137 ± 110, and 120 ± 153 vs. 290 ± 161, 300 ± 162, and 293 ± 190, respectively (p < 0.05 for all time points). Close monitoring of EBV viral load by qPCR and the degree of immunosuppression via ImmuKnow may guide physicians to reach the diagnosis of PTLD early.     

Sirolimus for pediatric liver transplant recipients with post-transplant lymphoproliferative disease and hepatoblastoma

Sirolimus is a promising immune suppressive agent, with the potential to reduce calcineurin inhibitor associated nephrotoxicity, halt progression of chronic rejection and prevent tumor proliferation. The aim of this study was to review the experience using sirolimus in pediatric liver transplant recipients at a single center. Database and medical charts of all pediatric liver transplant recipients receiving sirolimus at the Hospital for Sick Children in Toronto were reviewed. Eight patients received sirolimus between October, 2000 and September, 2002. Indications for using sirolimus were post-transplant lymphoproliferative disease (PTLD) (n = 6) and hepatoblastoma (n = 2). Two patients with PTLD concurrently had renal impairment and chronic rejection. Sirolimus dosages ranged between 1.5 and 5 mg once daily. Median duration of follow-up was 17 months. Persistently elevated liver transaminase levels in the two children with chronic rejection decreased during sirolimus therapy. Recurrence of PTLD occurred in one patient. Two patients were diagnosed with acute cellular rejection after transition to maintenance sirolimus monotherapy. Resolution of adverse effects including mouth sores (n = 3), leg swelling (n = 2) and hyperlipidemia (n = 3) occurred either spontaneously or with dose reduction. Sirolimus was discontinued in four patients because of persisting bone marrow suppression, interstitial pneumonitis, life-threatening sepsis and refractory diarrhea. Children with PTLD or hepatoblastoma may benefit from immune suppression with sirolimus after liver transplantation. Further multi-center, prospective, randomized controlled trials will be instrumental to further the knowledge of long-term efficacy, safety and tolerability of sirolimus for selected children following liver transplantation.