Risk Of Post-transplant Lymphoproliferative Disease Research Articles

Post-transplantation Lymphoproliferative Disease

Elevation in Epstein-Barr virus (EBV) circulating DNA has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but few published data exist in the study of lung-transplant recipients. To determine if elevated EBV DNA levels, in combination with other risk factors, were predictive of PTLD. We conducted a retrospective, single-center study examining all lung transplant recipients (n = 296) and EBV DNA levels (n = 612) using real-time TaqMan polymerase chain reaction. There were 13 cases of PTLD overall, of which 5 occurred in the era of EBV DNA monitoring. EBV DNA levels were distributed differently among seropositive and seronegative patients, with the latter having higher values (P < 0.0001). Among the cohort of pretransplantation seropositive patients, there was one diagnosed with PTLD. The EBV DNA level in this patient was elevated at the time of PTLD diagnosis (sensitivity = 100%, specificity = 100% for PTLD). Among the cohort of pretransplantation seronegative patients, there were four with a diagnosis of PTLD. In all four patients, the EBV DNA level was detectable (sensitivity = 100%, specificity = 24%), but in only two was it elevated (sensitivity = 50%, specificity = 22%). HLA-A3 expression in the recipient and/or donor conferred additional risk for PTLD among the seronegative patients (P = 0.026 to 0.003). No other PTLD risk factor was found. EBV DNA levels are a useful but imperfect predictor of PTLD in patients with lung transplants. Pretransplant EBV status affected the results of the assay and should be considered when interpreting test results. HLA-A3 was strongly linked to PTLD and may be a novel marker of PTLD risk.

End‐stage Liver Disease and Liver Transplant: Current Situation and Key Issues

The aim of this article is to identify the current challenges in pediatric OLT. It is directed to all physicians who care for pediatric patients from the early prospect of liver transplant to posttransplant life. Besides assessing current information on transplant results, the coauthors of this article have identified a number of issues that they consider as the most important that need to be addressed in 2008. Some are only an update of old questions, and others are newly identified problems. The recommendations from the group are summarized at the end of each specific issue and in the consensus guidelines.

Persistent detection of Epstein-Barr virus DNA after pediatric liver transplantation: Unclear risks and uncertain responses

Persistent detection of Epstein-Barr virus DNA after pediatric liver transplantation: Unclear risks and uncertain responses

Syndromes lymphoprolifératifs après transplantation rénale : incidence et particularités cliniques et évolutives

The aim of this study was to determine the epidemiological and the clinical characteristics of post-transplant lymphoproliferative disease (PTLD) and to evaluate its impact on patients' and grafts' survival. Three hundred and sixteen adult kidney recipients, transplanted between June 1986 and May 2006, were included. The incidence rates were calculated by dividing the number of different events (PTLD, death and graft-loss) by the total duration of follow-up. The survival rates and the cumulated frequency of PTLD were calculated according to the actuarial method. Seven recipients developed PTLD during a cumulated follow-up of 2202 years. The annual incidence was of 0.32% (95% CI : 0.30-0.34). It was of 0.81% (0.70-0.92) in recipients of kidneys from deceased donors, and of 0.25% (0.23-0.27) in patients transplanted from living donors (NS). The delay after transplantation for the diagnosis of PTLD ranged from 7.4 months to 7.7 years. PTLD was a B cell lymphoma in six cases and affected extra nodal sites in most of the cases. The treatment, comprising the cessation of immunosuppressive therapy in all cases, resulted in complete remission in four patients. Three patients died, representing an annual death rate of 6.1%, versus 2.8% in patients without PTLD (NS). The annual incidence of graft loss was 6.1% versus 3.2% among patients without PTLD (NS). PTLD was observed in 2.2% of our patients, with an annual incidence of 0.32%. It resulted in a decrease of both patients' and grafts' survivals. Preventive measures, including the improvement of the monitoring of immunosuppressive drugs and the prevention of viral infections, should be considered to reduce the risk of PTLD.

Quantification of Epstein-Barr Virus–DNA Load in Lung Transplant Recipients: A Comparison of Plasma versus Whole Blood

Monitoring of the Epstein-Barr virus-DNA load is frequently used to identify patients at risk for post-transplant lymphoproliferative disease (PTLD). Epstein-Barr virus DNA can be measured in the plasma and whole blood serum compartments. We compared levels of Epstein-Barr virus DNA in whole blood and plasma using a real-time TaqMan polymerase chain reaction assay in 100 consecutive paired whole blood and plasma samples from 25 lung and heart-lung transplant recipients with detectable whole blood Epstein-Barr virus-DNA load (>2,000 copies/ml). A correlation (r2) of 0.58 (p < 0.001) was observed between both measurements, whereas of the positive whole blood samples (>2,000 copies/ml), only 17 samples (18%) were also positive in plasma. These results indicate that by virtue of its sensitivity, whole blood rather than plasma may be the preferable specimen for the detection of Epstein-Barr virus DNA in lung transplant recipients.

Dissociation of Depletional Induction and Posttransplant Lymphoproliferative Disease in Kidney Recipients Treated With Alemtuzumab

Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.

Tonsil enlargement after liver transplantation in adults—reason enough for tonsillectomy? Two cases of tonsillar posttransplantation lymphoproliferative disease

Posttransplantation lymphoproliferative disease (PTLD) is a well-known complication of solid organ and bone marrow transplantation. It is agreed that the main causes of PTLD are chronic infection with Epstein-Barr virus (EBV); the intensity, rather then the type, of immunosuppression used; and underlying recipient disease. Hepatitis C virus (HCV) and cytomegalovirus, as cofactors of EBV infection, have been suggested to increase the risk of PTLD. Use of calcineurin inhibitors, anti-CD3 monoclonal antibody (OKT3), and antithymocyte globulin may increase the risk of PTLD. On the other hand, mycophenolate mofetil, sirolimus, and the anti-interleukin-2 receptor monoclonal antibodies Daclizumab and basiliximab have not been demonstrated to increase the risk of PTLD. The incidence of PTLD after liver transplantation (LT) is estimated to be 1.5-3%, but a tonsillar location is extremely rare in adults. Thus, little is known about the best diagnostic tools for and treatment by LT recipients with tonsillar PTLD. Here, we report 2 cases of adult LT recipients with tonsillar PTLD. Tonsillectomy was used as a diagnostic tool and treatment option and resulted in complete remission for >2 years. Considering the high mortality and diagnostic difficulties of PTLD, together with the relatively low risks of tonsillectomy, we recommend tonsillectomy for treating tonsil enlargement of unknown cause and suspected PTLD in LT recipients. A larger series of patients and prospective studies comparing different treatment options will be needed to substantiate our recommendation.

Aciclovir and ganciclovir prophylaxis is effective in reducing the risk of post-transplant lymphoproliferative disease (PTLD)

Aciclovir and ganciclovir prophylaxis is effective in reducing the risk of post-transplant lymphoproliferative disease (PTLD)

Post-Transplant Lymphoproliferative Disease

In the last 2 decades, several polyclonal and monoclonal antibodies have been developed for induction therapy in the early post solid-organ transplantation period. The use of these antibodies has been associated, for the most part, with a decrease in early acute rejection rates. However, there has been a simultaneous rise in infectious complications, particularly in the incidence of post-transplant lymphoproliferative disease (PTLD). Determinations of adjusted odds ratios or relative risk have yielded conflicting information regarding whether these antibody agents increase the risk for PTLD. In order to interpret the results of the different studies, the reader requires a detailed knowledge of the types of analyses performed and the characteristics of the populations studied. This article analyses the available data on PTLD risk after the use of induction antibody agents. While some studies suggest an increased risk of PTLD after induction antibody use, other studies do not; the available data are not conclusive either way at this time.

Induction of pre‐transplant Epstein–Barr virus (EBV) infection by donor blood transfusion in EBV–seronegative recipients may reduce risk of post‐transplant lymphoproliferative disease in adolescent renal transplant patients: report of two cases

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication following organ transplantation. The greatest risk is seen in Epstein-Barr virus (EBV)-seronegative patients receiving allografts from EBV-seropositive donors. We demonstrate a new approach of pre-transplant prophylaxis of EBV-related PTLD, suggesting that, prior to living-related renal transplantation, blood transfusion from an EBV-seropositive donor to an EBV-seronegative recipient could induce primary EBV infection in the recipient, developing EBV immunity and decreasing risk of PTLD. Recipients underwent weekly donor-specific blood transfusion (3 x 100 mL) before transplantation. EBV-mRNA expression, viral load, serological tests, and clinical signs of EBV infection were assessed following blood transfusion. We explored a new approach in 2 young EBV-seronegative renal allograft recipients. Both patients developed primary EBV infection following blood transfusion before transplantation and showed symptom-free seroconversion post-transplantation without persistent EBV activation. There were no signs of PTLD during 5-year follow-up. A new effective and inexpensive approach is suggested for development of EBV immunity and probably for prophylaxis of EBV-associated PTLD.

Antibody Induction Therapy in Renal Transplant Patients Receiving Calcineurin-Inhibitor Immunosuppressive Regimens

Acute rejection during the first year post-transplant is a key predictor of graft survival after renal transplantation. Use of induction therapy with a lymphocyte-depleting agent or an interleukin-2 receptor (IL-2R) antagonist can provide effective protection against rejection in the first critical weeks and months post-transplant. Polyclonal lymphocyte-depleting antibodies are associated with a low incidence of rejection but evidence of their benefit in terms of graft survival is lacking. Thymoglobulin appears to offer superior graft outcomes compared with generic antithymocyte globulin (ATG). The most frequent adverse events are symptoms of cytokine release syndrome, leukopenia, thrombocytopenia, and tachycardia; data on whether polyclonal antibody use increases the risk of lymphoma are conflicting. Muromonab CD3 (OKT3), a monoclonal lymphocyte-depleting antibody, is efficacious but a high incidence of cytokine release syndrome and increased risk of post-transplant lymphoproliferative disease have limited its use. Following their recent introduction, the IL-2R antagonists basiliximab and daclizumab are now used widely, after randomized trials demonstrated that addition to calcineurin inhibitor-based therapy significantly reduced acute rejection by approximately 30-40%. Meta-analyses and registry analysis suggest that addition of an IL-2R antagonist may improve graft survival. The safety profile of IL-2R antagonists is indistinguishable from placebo, with no apparent difference in incidence of infection or post-transplant lymphoproliferative disease. IL-2R antagonists and polyclonal lymphocyte-depleting antibodies (with delayed cyclosporine) offer equivalent efficacy in standard-risk populations; in a trial of high-risk patients, acute rejection rate and graft outcomes were improved with Thymoglobulin. Tolerability is superior with IL-2R antagonists: cytokine release syndrome and hematologic disturbances (notably leukopenia) are significantly more frequent with polyclonal antibodies. Cytomegalovirus infection may also be more common with lymphocyte-depleting antibodies. Thus, in patients at high risk of graft loss, Thymoglobulin may be the preferred choice for induction therapy, while for all other patients, IL-2R antagonists should be considered first-line choice for induction therapy.

Surface Immunoglobulin-Deficient Epstein-Barr Virus-Infected B Cells in the Peripheral Blood of Pediatric Solid-Organ Transplant Recipients

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, normally causes an asymptomatic latent infection with very low levels of circulating virus in the peripheral blood of infected individuals. However, EBV does have pathogenic potential and has been linked to several diseases, including posttransplant lymphoproliferative disease (PTLD), which involves very high circulating viral loads. As a consequence of immunosuppression associated with transplantation, children in particular are at risk for PTLD. Even in the absence of symptoms of PTLD, very high viral loads are often observed in these patients. EBV-infected B cells in the circulations of 16 asymptomatic pediatric solid-organ transplant recipients from Children's Hospital of Pittsburgh were simultaneously characterized for their surface immunoglobulin (sIg) isotypes and EBV genome copy numbers. Patients were characterized as having high and low viral loads on the basis of their stable levels of circulating virus. Patients with high viral loads had both high- and low-copy-number cells. Cells with a high numbers of viral episomes (>20/cell) were predominantly Ig null, and cells with low numbers of episomes were predominantly sIgM positive. Patients with low viral loads carried the vast majority of their viral load in low-copy-number cells, which were predominantly IgM positive. The very rare high-copy-number cells detected in carriers with low viral loads were also predominantly Ig-null cells. This suggests that two distinct types of B-lineage cells contribute to the viral load in transplant recipients, with cells bearing high genome copy numbers having an aberrant Ig-null cellular phenotype.

Long-term follow-up of Epstein-Barr virus viremia in pediatric recipients of renal transplants

The common observation of Epstein-Barr virus (EBV) viremia in pediatric recipients of renal transplants and the occurrence of an EBV-related pulmonary leiomyoma prompted us to intensify the follow-up of EBV infections from 1995 to October 2000. Follow-up included serology and detection of viral DNA in blood using a semi-quantitative nested polymerase chain reaction (PCR) and later a real-time PCR with higher sensitivity. The aim of this study was the early detection of primary infections or reactivations. We obtained 250 samples from 32 patients. EBV DNA detection was consistently negative in 14 patients. There were 5 patients that were considered at risk for post-transplant lymphoproliferative disease, as they were EBV seronegative and were given a kidney from a positive donor. Of these, 4 had at least one episode of high-level EBV viremia. During these episodes, an absence of noticeable symptoms that could be related to EBV was noted for all but 1 patient. This child presented with severe neutropenia 1 month after grafting and, 28 months later, several nodules of pulmonary leiomyoma, which were found to be EBV related. Four episodes of high-level viremia were observed before the discovery of the leiomyoma. Viral DNA detection is important for the follow-up of such patients that are especially at risk of serious complications of EBV infections.

Epstein-Barr virus primary mismatching and HLA matching: key risk factors for post lung transplant lymphoproliferative disease.

Posttransplant lymphoproliferative disease (PTLD) in lung transplant recipients (LTRs) is potentially lethal with considerable morbidity. The role of donor (D)/recipient (R) HLA matching is unknown. We reviewed our LTRs from January 1994, when routine D/R Epstein-Barr virus (EBV) serologic screening was begun, through to January 2000. We examined whether D/R HLA match status influenced the risk of PTLD in EBV D+/R- mismatched LTRs. There were 16 D+/R- EBV-mismatched LTRs, 5 (31%) of whom developed PTLD (from a total of 237 LTRs; 218 survived >30 days). There were only two other cases of PTLD among the non-EBV primary mismatched patients. All patients received baseline immunosuppression of cyclosporine, azathioprine, and prednisolone without cytolytics and ganciclovir prophylaxis if "at risk" from cytomegalovirus. The five PTLD cases were diagnosed 81 to 734 (median 116) days from transplantation; three involved the lung allograft and two others involved lymph nodes. All PTLD patients seroconverted for EBV, whereas 7 of the 11 remaining EBV-mismatched patients who did not develop PTLD did not seroconvert. In the 16 EBV primary mismatched patients, there were 4 of 66 HLA allele matches in the 11 PTLD-free patients versus 15 of 30 matches in the 5 PTLD patients (P<0.001). This resulted in 2 or more HLA (A/B/DR) matches in 4 of 5 patients with PTLD versus 0 of 11 in the PTLD-free group (P=0.003). All PTLD patients were treated with reduced immunosuppression and antiviral therapy. Only two of the five LTRs who developed PTLD died, one with progressive disease despite chemotherapy and the other from chronic allograft rejection. A high degree of HLA matching in D/R EBV-mismatched LTRs significantly increases the risk of PTLD.

The value of prospective monitoring of Epstein-Barr virus DNA in blood samples of pediatric liver transplant recipients.

Post-transplant lymphoproliferative disease (PTLD) is one of the major causes of morbidity and mortality in transplantation patients. A primary Epstein-Barr virus (EBV) infection is a major risk factor for developing PTLD. The aim of this study was to determine circulating EBV DNA after liver transplantation in pediatric patients in relation to primary EBV infection and development of PTLD. EBV serology was performed before transplantation. Every 4 weeks after transplantation a competitive quantitative polymerase chain reaction (PCR) assay for EBV nuclear antigen-1 was performed in 13 patients. Patients were followed for development of a PTLD. Before transplantation four patients were EBV seropositive and nine patients were EBV seronegative. In one of the four patients who were EBV seropositive before transplantation, EBV DNA became detectable after transplantation, with a peak load of 3600 copies/mL. None of these four patients developed a PTLD. Eight of the nine patients who were EBV seronegative before transplantation developed positive EBV DNA samples. EBV DNA was first detected at a mean of 64 days after transplantation (range 38-89). The mean peak EBV DNA load was 79,700 copies/mL (3600-446,000). Two of these patients developed PTLD, but they could not be identified based on prior or concomitant EBV PCR results. In pediatric liver transplantation EBV DNA load is higher in patients with a primary infection than in patients who were EBV seropositive before transplantation. The EBV PCR cannot be used to identify individual patients who develop PTLD. However, elevated EBV DNA load can be used to detect a group of patients at increased risk for PTLD.

Epstein‐Barr Virus (EBV) Early‐Antigen Serologic Testing in Conjunction with Peripheral Blood EBV DNA Load as a Marker for Risk of Posttransplantation Lymphoproliferative Disease

Epstein-Barr virus (EBV) early-antigen (EA) serologic profile was examined in conjunction with peripheral blood EBV DNA load, to assess its value in evaluating the risk of developing posttransplantation lymphoproliferative disease (PTLD). The cohort included 26 pediatric recipients of solid-organ transplants, 6 of whom developed PTLD. All 6 patients had high peripheral blood EBV DNA loads. Of the remaining 20 patients who did not develop PTLD, 14 had high EBV DNA loads, and 6 had low EBV DNA loads. None of the patients who developed PTLD had significant EA immunoglobulin G (IgG) titers. However, all 14 patients with high EBV DNA loads and without PTLD had high EA IgG titers, either at the time of initial high EBV DNA load or during the ensuing weeks. Here, we report that EBV DNA load analysis, combined with EA serologic analysis, is a potentially useful prognostic marker for evaluating the risk of developing PTLD.

Ratio between Epstein-Barr viral load and anti-Epstein-Barr virus specific T-cell response as a predictive marker of posttransplant lymphoproliferative disease.

Posttransplant lymphoproliferative disease (PTLD) is closely linked to primary Epstein-Barr virus (EBV) infection and a defect of EBV specific cellular immunity is supposed to be the basis of PTLD. However, EBV load is so far the only marker proposed to evaluate PTLD risk, and no study has investigated the role of specific anti-EBV T lymphocytes (EBV-TL). We therefore prospectively measured the EBV-TL by enzyme-linked immunospot (elispot) assay, in correlation to EBV load by real-time quantitative PCR and lymphoproliferation occurrence in 45 liver transplanted children. EBV load at the time of primary infection was high in all patients irrespective to subsequent emergence of PTLD. Seven patients developed PTLD, all of them following primary EBV infection. All seven had low EBV-TL (<2/mm3) associated with high viral load (>25,000 copies/microg DNA). Both parameters can be combined in a 100% positive predictive index. Healing from lymphoma was characterized by rapid EBV-TL increase concomitant to decreasing viral load. EBV-TL follow-up helped to adapt immunomodulation. No patient had PTLD whenever EBV-TL were above 2/mm3. We conclude that high viral load is systematic in patients who underwent primary EBV infection and is indicative of the PTLD risk only if there is low concomitant cellular immune response. Healing from PTLD requires modulation of immunosuppression, and appearance of EBV-TL.

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.

Patients at risk for post-transplant lymphoproliferative disease can be identified in the first months after lung transplantation by quantitative-competitive-EBV-PCR

Introduction: Epstein-Barr virus (EBV) is associated with Post Transplant Lymphoproliferative Disease (PTLD). To investigate if patients at risk for PTLD can be identified early we measured the EBV viral load during the first 8 months after lung transplantation (Ltx). In addition we studied immunosuppression as a risk factor for PTLD.

Pediatric lung transplantation and CMV pneumonitis: a ten year experience

Cytomegalovirus (CMV) infection remains an important source of morbidity after solid organ transplantation. To understand the impact of CMV pneumonitis in pediatric lung transplant recipients, we conducted a prospective study of 194 pediatric patients receiving 218 lung transplants. Medical records of pediatric patients undergoing transplantation at Saint Louis Children’s Hospital between 1990 and September 2000 were reviewed after Institutional Review Board approval. Data was analyzed using survival analysis. 194 patients underwent primary transplants and 24 were re-transplants. 86 male & 108 female patients were tracked for an average of 2.7 years (range: 1 day − 9.7 years). 46.6% had cystic fibrosis, 26.9% had pulmonary hypertension and 26.4% had other pulmonary diseases. All CMV-seropositive recipients (R+) and all CMV-seronegative recipients who received CMV-seropositive organs (R-/D+) were treated with gancyclovir prophylaxis for a total of six weeks post transplant. Histologic evidence of CMV pneumonitis was observed in 32 patients (16.5%). Survival analysis identified that the only risk factors for CMV pneumonitis were CMV donor and recipient seropositive status. R-/D+ were at 6.1 times (95% confidence interval (CI): 2.0-18.1) increased risk of developing subsequent CMV. The increase in risk was 3.2 (95% CI: 0.9-11.0) for D+/R+. No increased risk was found among R+/D-: (relative risk=2.3; 95% CI: 0.6-9.2). Sex, age , primary diagnosis and a second transplant were not risk factors for development of CMV pneumonitis. Of all patients with CMV pneumonitis, 7 subsequently developed post-transplant lymphoproliferative disease (PTLD) and 11 developed bronchiolitis obliterans (BO).CMV pneumonitis did not increase the risk of PTLD (relative risk=1.9;95%CI:0.7-5),BO (relative risk=1.0;CI:0.5-2.0), or overall mortality (relative risk 1.0;95%CI:0.6-1.7). In our pediatric population the highest risk for CMV pneumonitis is associated with a CMV+ donor but CMV pneumonitis does not appear to be a risk factor for mayor complications or mortality. Thus, these data do not support matching CMV status between donor and recipient.