Posttransplantation lymphoproliferative disorders in pediatric thoracic organ recipients

Boyle, Gerard J.; Michaels, Marian G.; Webber, Steven A.; Knisely, A. S.; Kurland, Geoffrey; Cipriani, Lynne; Griffith, Bartley P.; Fricker, Frederick J.

doi:10.1016/s0022-3476(97)70173-2

Cited by 137 publications

(107 citation statements)

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“…Case 17 was particularly instructive in the observation of EB virus sero-conversion 2 weeks after transplanta- tion, and 7 months before development of an EBVpositive form of PTLD. This is highly reminiscent of the pathogenetic sequence described in children who developed PTLD after post transplant primary EB virus infection [17]. Unfortunately, because donor and recipient EB virus testing was not a mandatory part of the work-up for all organ-transplant programs, it was not possible to asses the impact of donor-recipient EB virus status mismatching on the risk of PTLD in this study.…”

Section: Discussionmentioning

confidence: 95%

Treatment and outcomes of post‐transplant lymphoproliferative disease: A single institution study

et al. 2006

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Post-transplant lymphoproliferative disorders (PTLD) complicate up to 10% of solid organ transplants. This retrospective study was conducted to review the PTLD experience among 2,300 recipients of solid organ or allogeneic bone marrow transplants from a single institution. Twenty-seven cases of PTLD were identified, leading to an overall incidence of 1.2%. Polymorphic B cell hyperplasia/lymphoma was the most common type. The median time to development of PTLD was 8.4 months. Ten patients had localized (stage I or II) disease, and 12 patients presented with B symptoms. Nine patients each were treated with systemic chemotherapy or surgical resection as part of the initial therapy. After a median follow-up duration of 2.6 years, the median survival has not been reached. There were no late relapses of PTLD, and 17 patients remain alive. Age, sex, organ source, LDH, stage, presence of extranodal disease, or presentation with B symptoms did not influence overall survival when examined by Cox proportional hazard model. Thirteen patients retained their graft function throughout PTLD treatment. This study confirms the ability to treat a significant proportion of PTLD patients with chemotherapy or surgical resection (depending on presentation), without sacrificing graft function in those receiving chemotherapy. Am. J. Hematol. 82:208-214, 2007. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Treatment and outcomes of post‐transplant lymphoproliferative disease: A single institution study

et al. 2006

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“…The incidence of EBV reactivation/PTLD in the pediatric patients (5.7%) was similar with other reports ranging from 5 to 12%. 19,20 Searching for associations between EBV-DNA loads and the clinical manifestation, PTLD patients had a higher median EBV-DNA level of 250 Geq/ml (range 100-100 000) when compared to patients with EBV reactivation who had a median level of 177 Geq/ml (range 100-10 400). It was interesting to note that one patient with EBV reactivation whose EBV-DNA level was410 000 Geq/ml did not develop PTLD, whereas another patient with PTLD showed only 100 Geq/ml EBV-DNA in the serum but developed colon perforation due to intestinal lymphoma infiltration.…”

Section: Discussionmentioning

confidence: 99%

EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT

Ocheni

Kroeger

Zabelina

et al. 2008

Bone Marrow Transplant

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Fatal problems encountered in allogeneic stem cell transplantation include EBV reactivation and post transplant lymphoproliferative disorders (PTLDs) with high mortality rates. We performed a retrospective analysis in all consecutive adult and pediatric EBV reactivations and PTLD during a period of 8.5 years. There were 26 patients with EBV reactivation/PTLD out of a total of 854 transplantations giving an overall incidence of 3.0%. Specifically, the incidence of EBV-PTLD was 1.3%, whereas that of EBV reactivation was 1.8%. Median age was 46.0 and 11.0 years in the adult and pediatric patients, respectively. There were high rates (54%) of concomitant bacterial, viral, fungal and parasitic infections at the time of EBV manifestation. Variable treatment regimens were applied including in most cases an anti-CD20 regimen often in combination with virustatic compounds, polychemotherapy or donor lymphocytes. The mortality rates were 9 of 11 (82%) in patients with EBV-PTLD and 10 of 15 (67%) in patients with reactivation. Only 7 of 26 patients (27%) are alive after a median follow-up of 758 days (range 24-2751). The high mortality rates of EBV reactivation and of EBV-PTLD irrespective of multimodal treatment approaches emphasize standardization and optimization of post transplant surveillance and treatment strategies to improve control of these often fatal complications.

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“…1 However, PTLD is more common in children, because many children are EBV-naive at the time of transplant. [2][3][4][5] Manifestations of PTLD are protean and include signs and symptoms of both focal disease, such as graft dysfunction, as well as systemic disease, eg, viral illness.…”

Section: P Osttransplant Lymphoproliferative Disorder (Ptld) Is Relatmentioning

confidence: 99%

“…[2][3][4][5] However, detailed autopsy reports of series of PTLD patients have not been reported. We present the pathology found at autopsy of 7 children who died with PTLD.…”

Section: P Osttransplant Lymphoproliferative Disorder (Ptld) Is Relatmentioning

confidence: 99%

Autopsy Pathology of Pediatric Posttransplant Lymphoproliferative Disorder

Collins

Montone

Leahey³

et al. 2001

Pediatrics

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ABSTRACT. Objectives. Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death.Methods. Postmortem examinations were performed on 7 patients after bone marrow (n ‫؍‬ 3) or liver (n ‫؍‬ 4) transplant. PTLD was classified histologically as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used to categorize infections as negative, primary, or reactive.Results. PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before death, and 1.5 to 4 (mean: 3) months after transplant; PTLD was diagnosed in 2 cases at autopsy 2.5 and 4 months after transplant. Postmortem PTLD histology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperplasia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not have EBV serology that indicated active infection. Complete autopsy of 4 patients who died with biopsy-proven PTLD revealed widely disseminated disease, and lymph node, brain, gastrointestinal tract, and kidney were involved in all 4 patients. Cases diagnosed at autopsy were 1 widely disseminated PTLD that had been suspected but not proven antemortem, and 1 PTLD confined to abdominal lymph nodes that was not suspected antemortem. Severe organ dysfunction (renal failure, gastrointestinal hemorrhage) was caused by massive PTLD infiltration in 2 patients. The conditions other than PTLD that contributed to morbidity and death were organ infection (5 cases), infarcts (4 cases), and diffuse alveolar damage (3 cases).Conclusions. PTLD may occur within weeks after transplant in children. The distribution of PTLD comprises a spectrum from localized and subclinical to widely disseminated and symptomatic. PTLD may cause demise quickly after the onset of signs and symptoms, through massive organ infiltration or associated conditions, such as diffuse alveolar damage. EBV serology may not accurately reflect the presence or extent of PTLD. Autopsy studies of transplant patients are necessary to identify the true incidence, natural history, and response to treatment of PTLD. Pediatrics 2001;107(6). URL: http:// www.pediatrics.org/cgi/content/full/107/6/e89; posttransplant lymphoproliferative disorder, autopsy, pediatric pathology, Epstein-Barr virus, lymphoma, mortality.ABBREVIATIONS. PTLD, posttransplant lymphoproliferative disorder; EBV, Epstein-Barr virus; CHOP, Children's Hospital of Philadelphia; LMP, latent membrane protein; Ig, immunoglobulin; VCA, viral capsid antigen; GI, gastrointestinal; PCR, polymerase chain reaction. P osttransplant lymphoproliferative disorder (PTLD) is related to Epstein-Barr virus (EBV)infecti...

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Posttransplantation lymphoproliferative disorders in pediatric thoracic organ recipients

Cited by 137 publications

References 5 publications

Treatment and outcomes of post‐transplant lymphoproliferative disease: A single institution study

Treatment and outcomes of post‐transplant lymphoproliferative disease: A single institution study

EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT

Autopsy Pathology of Pediatric Posttransplant Lymphoproliferative Disorder

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