Clinicopathologic features of post‐transplant lymphoproliferative disorders arising after pediatric small bowel transplant

Nassif, Samer; Kaufman, Stuart S.; Vahdat, Sadaf; Yazigi, Nada; Kallakury, Bhaskar; Island, Eddie; Özdemirli, Metin

doi:10.1111/petr.12150

Cited by 28 publications

(18 citation statements)

References 19 publications

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“…Post-transplant lymphoproliferative disease developed in 18% of patients in our study, which is slightly higher than the reported incidence of about 10%-13% [12][13][14] and may be due to differing immunosuppressive regimens between institutions or the types of transplanted grafts utilized. Similar to others, PTLD in our study occurred more often in pediatric patients, was frequently associated with EBV infection, and most patients had evidence of ACR prior to development of PTLD.…”

Section: Discussioncontrasting

confidence: 73%

Allograft biopsy findings in patients with small bowel transplantation

Koo

Dawson

Dry

et al. 2016

Clinical Transplantation

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In this study, we sought to determine the incidence of post-transplant complications including acute cellular rejection (ACR), infection, and post-transplant lymphoproliferative disease (PTLD) in mucosal allograft biopsies in patients with small bowel transplant at our institution. We retrospectively reviewed pathology reports from 5675 small bowel allograft biopsies from 99 patients and analyzed the following: indications for biopsy, frequency and grade of ACR, the presence of infectious agents, results of workup for potential PTLD, results of C4d immunohistochemistry (IHC), features of chronic mucosal injury, and findings in concurrent native bowel biopsies. Findings from 42 allograft resection specimens were also correlated with prior biopsy findings. Indeterminate, mild, moderate, and severe ACR were seen in 276 (4.9%), 409 (7.2%), 100 (1.8%), and 207 (3.6%) of biopsies, respectively. Although ACR may show histologic overlap with mycophenolate mofetil toxicity, we found the analysis of concurrent native bowel biopsies to be helpful in this distinction. Adenovirus was the most common infectious agent seen (11%), and we routinely performed adenovirus IHC on biopsies. Eighteen patients (18%) developed PTLD, 83% of which were EBV associated, but only 28% of PTLD cases were diagnosed on mucosal allograft biopsies. C4d IHC did not correlate with the presence of donor-specific antibodies in limited cases.

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Section: Discussioncontrasting

confidence: 73%

Allograft biopsy findings in patients with small bowel transplantation

Koo

Dawson

Dry

et al. 2016

Clinical Transplantation

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“…However, each of these patients also received sirolimus with standard-exposure CNI, a combination which has been associated with an unacceptably high rate of PTLD in children undergoing kidney transplantation and, indeed, led to premature discontinuation of one study due to PLTD risk [79]. It seems likely that these children undergoing small bowel transplant were over-immunosuppressed, contributing to the high rate of PTLD [77].…”

Section: Retrospective Studiesmentioning

confidence: 96%

“…The limited available retrospective data from liver [78] and lung [76] patients also show no effect of rATG therapy on risk of PTLD. In small bowel transplantation, one series has reported an increased rate of PTLD in a series of children given rATG induction at a cumulative dose of 7.5 mg/kg [77]. rATG in this study was given to the 16 patients who had high titers of de novo donor-specific antibodies (DSA) (n = 11) or to treat rejection (n = 5).…”

Section: Retrospective Studiesmentioning

confidence: 97%

Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

Hertig

Zuckermann

2015

Transplant Immunology

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The most modifiable risk factor for post-transplant lymphoproliferative disease (PTLD) is the type and dose of induction and maintenance immunosuppressive therapy. It is challenging to identify the contribution of a single agent such as rabbit antithymocyte globulin (rATG) in the setting of multidrug therapy. Registry analyses can be helpful but are limited by methodological restrictions and inclusion of historical patient cohorts. These are typically from eras when rATG dosing was markedly higher than current dosing (e.g. total dose 14 mg/kg versus 6 mg/kg now), accompanied by higher exposure to maintenance therapies, and often an absence of antiviral prophylaxis. The largest registry analysis to assess rATG specifically found no risk of PTLD after kidney transplantation, but conflicting results have been reported, highlighting the difficulty of interpreting this type of analysis. The relative rarity of PTLD means that individually controlled trials are underpowered to assess its occurrence, but the available data do not suggest an effect of rATG. A pooled analysis of data from studies of rATG induction in kidney and heart transplantation found the incidence of PTLD to be comparable to published reports in the overall transplant population. Data on the effect of rATG dose are inconclusive, but in patients receiving antiviral prophylaxis it does not appear to be influential. Nevertheless, it would seem reasonable to employ the lowest dose of rATG compatible with effective induction, particularly in EBV-seronegative recipients and other high-risk groups such as heart-lung transplant recipients. Overall, the risk of PTLD following rATG induction therapy with modern dosing regimens and under current management conditions appears unlikely to make an important contribution to the risk:benefit balance.

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“…The single-center experience published by Nassif et al 6 suggests that the combination of ATG and sirolimus may be linked to more clinically and histologically advanced PTLD. This did not appear to be the case in our experience, possibly because MMF in addition to tacrolimus is our typical maintenance immunosuppression, with sirolimus used for rescue therapy when indicated.…”

Section: Itx Compared With What Has Been Previously Reported In Previousmentioning

confidence: 99%

Clinical characteristics and outcomes of PTLD following intestinal transplantation

Wozniak

Mauer

Venick

et al. 2018

Clinical Transplantation

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Post-transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single-center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy-proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow-up time of 6.4 (1.6-14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re-ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.

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Clinicopathologic features of post‐transplant lymphoproliferative disorders arising after pediatric small bowel transplant

Cited by 28 publications

References 19 publications

Allograft biopsy findings in patients with small bowel transplantation

Allograft biopsy findings in patients with small bowel transplantation

Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: An update

Clinical characteristics and outcomes of PTLD following intestinal transplantation

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