Post-transplant lymphoproliferative disorder after lung transplantation: A review of 35 cases

doi:10.1016/j.healun.2011.10.013

The Journal of Heart and Lung Transplantation

Volume 31, Issue 3, March 2012, Pages 296-304

https://doi.org/10.1016/j.healun.2011.10.013 Get rights and content

Background

Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation. The risk of developing PTLD varies depending on a number of factors, including the organ transplanted and the degree of immunosuppression used.

Methods

We report a retrospective analysis of 35 patients with PTLD treated at our center after lung transplantation. Of 705 patients who received allografts, 34 (4.8%) developed PTLD. One patient underwent transplantation elsewhere and was treated at our center.

Results

PTLD involved the allograft in 49% of our patients and the gastrointestinal (GI) tract lumen in 23%. Histologically, 39% of tumors were monomorphic and 48% polymorphic. The time to presentation defined the location and histology of disease. Of 17 patients diagnosed within 11 months of transplantation, PTLD involved the allograft in 12 (71%) and the GI tract in 1 (p = 0.01). This “early” PTLD was 85% polymorphic (p = 0.006). Conversely, of the 18 patients diagnosed more than 11 months after transplant, the lung was involved in 5 (28%) and the GI tract in 7 (39%; p = 0.01). “Late” PTLD was 71% monomorphic (p = 0.006). Median overall survival after diagnosis was 18.57 months. Overall survival did not differ between all lung transplant recipients and those who developed PTLD.

Conclusions

PTLD is an uncommon complication after lung transplantation, and its incidence declined remarkably in the era of modern immunosuppression. We report several factors that are important for predisposition toward, progression of, and treatment of PTLD after lung transplantation.

Section snippets

Materials and methods

The records of all lung transplant patients treated for PTLD at the HUP Abramson Cancer Center were reviewed. All patients received induction immunosuppression with anti-thymocyte globulin (ATG), daclizumab, or basiliximab. Maintenance immunosuppression regimens included a combination of prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus) and an anti-proliferative agent (azathioprine, mycophenolate mofetil [MMF], or sirolimus).

The presence of disease was confirmed in all patients

Patient characteristics

Between December 1991 and March 2011, 705 patients underwent lung transplantation at the HUP and PTLD developed in 34 (4.8%). One additional patient underwent transplantation at another institution but was treated for PTLD at HUP. Characteristics of our PTLD population are summarized in Table 1. The median age of patients at transplantation of 52 years (range, 21–65 years), and 17 (49%) were women. The most common indication for transplantation was chronic obstructive pulmonary disease,

Discussion

Solid organ transplantation is a well-known risk factor for malignancy.²⁴ It has been postulated that this is due to decreased immunologic surveillance as a consequence of post-transplant immunosuppression.3, 24, 25, 26, 27 One complication of transplantation is PTLD, which has been observed with varying frequency after every type of solid organ transplantation. Although PTLD is more commonly observed after lung transplantation than with other organs,⁶ it is still a rare disease, with very few

Disclosure statement

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

References (47)

A.W. Loren et al.
Post-transplant lymphoproliferative disorder
Clin Chest Med
(2005)
S. Paranjothi et al.
Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases
J Heart Lung Transplant
(2001)
B.D. Reams et al.
Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients
Chest
(2003)
R. Reshef et al.
Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder
Am J Transplant
(2011)
T.E. Starzl et al.
Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy
Lancet
(1984)
R.L. Elstrom et al.
Treatment of PTLD with rituximab or chemotherapy
Am J Transplant
(2006)
J.F. Buell et al.
Chemotherapy for posttransplant lymphoproliferative disorder: the Israel Penn International Transplant Tumor Registry experience
Transplant Proc
(2005)
L.J. Swinnen et al.
Aggressive treatment for postcardiac transplant lymphoproliferation
Blood
(1995)
D.A. Hale
Biological effects of induction immunosuppression
Curr Opin Immunol
(2004)
J.S. Hawksworth et al.
New directions for induction immunosuppression strategy in solid organ transplantation
Am J Surg
(2009)

R. Lischke et al.

Induction therapy in lung transplantation: initial single-center experience comparing daclizumab and antithymocyte globulin

Transplant Proc

(2007)

J.C. Mullen et al.

A randomized, controlled trial of daclizumab vs anti-thymocyte globulin induction for lung transplantation

J Heart Lung Transplant

(2007)

S. Caillard et al.

Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry

Am J Transplant

(2006)

A.D. Kirk et al.

Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab

Am J Transplant

(2007)

W. Bichari et al.

Significant risk factors for occurrence of cancer after renal transplantation: a single center cohort study of 1265 cases

Transplant Proc

(2009)

G. Opelz et al.

Lymphomas after solid organ transplantation: a collaborative transplant study report

Am J Transplant

(2004)

W.K. Kremers et al.

Post-transplant lymphoproliferative disorders following liver transplantation: incidence, risk factors and survival

Am J Transplant

(2006)

S. Wasson et al.

Post-transplantation lymphoproliferative disorder in heart and kidney transplant patients: a single-center experience

J Cardiovasc Pharmacol Ther

(2006)

S. Gottschalk et al.

Post-transplant lymphoproliferative disorders

Annu Rev Med

(2005)

D.A. Wigle et al.

Epstein-Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation

Transplantation

(2001)

F.K. Buadi et al.

Treatment and outcomes of post-transplant lymphoproliferative disease: a single institution study

Am J Hematol

(2007)

N.A. Bakker et al.

Early onset post-transplant lymphoproliferative disease is associated with allograft localization

Clin Transplant

(2005)

van Loenhout KC, Groves SC, Galazka M, et al. Early outcomes using alemtuzumab induction in lung transplantation....

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The post-transplant lymphoproliferative disorders (PTLDs) are a family of conditions that are heterogeneous in presentation, morphology, and prognosis, and are often associated with EBV. While these entities may involve any anatomic site, including but not limited to the graft itself, the GI tract represents one of the most common organs affected.84–89 PTLD typically occurs within the first year after hematopoietic stem cell transplant and within the first 4–5 years after solid organ transplant, but late cases have been reported a decade or more after transplant.85,90,91
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Original clinical sciencePost-transplant lymphoproliferative disorder after lung transplantation: A review of 35 cases

Background

Methods

Results

Conclusions

Section snippets

Materials and methods

Patient characteristics

Discussion

Disclosure statement

Clin Chest Med

J Heart Lung Transplant

Chest

Am J Transplant

Lancet

Am J Transplant

Transplant Proc

Blood

Curr Opin Immunol

Am J Surg

Transplant Proc

J Heart Lung Transplant

Am J Transplant

Am J Transplant

Transplant Proc

Am J Transplant

Am J Transplant

Post-transplantation lymphoproliferative disorder in heart and kidney transplant patients: a single-center experience

J Cardiovasc Pharmacol Ther

Post-transplant lymphoproliferative disorders

Annu Rev Med

Epstein-Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation

Transplantation

Treatment and outcomes of post-transplant lymphoproliferative disease: a single institution study

Am J Hematol

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Clin Transplant

Original clinical science
Post-transplant lymphoproliferative disorder after lung transplantation: A review of 35 cases