Diagnosis & treatment of PTLD

1. Diagnosis & treatment
of PTLD
Dr MOHAMMED YASSINE KENIZ

2. Introduction
• A monoclonal or polyclonal lymphoid proliferation that occurs following solid organ
transplantation SOT.
• Uncontrolled hyperplasia of lymphoid tissues
• A post-transplant EBV lymphomas.
• Association reactivation EBV and the post-transplant lymphoproliferative disorder PTLD:
incidence 120 cases/10,000p/y.
Deficiency of cytotoxic T lymphocytes.
Lack of adapted T response.
Proliferation of B lymphocytes(donor origin)
Mortality 50% and Second to skin cancer in
adults

3. Risk factors
• Several risk factors are in favour of PTLD; such as mainly infection in most case by
Epstein-Barr virus EBV, degree and duration of immunosuppression, age, race of
recipient, type of allograft and genetic factors.
• Early PTLD:
Primary EBV infection
Young recipient age
CMV mismatch or CMV disease
OKT3 and polyclonal antilymphocyte
antibodies
• Late PTLD:
 Duration of Immunosuppression
 Type of organ transplanted
 Older recipient age

4. Physiopathology
• The degree of immunosuppression used in lung, heart, intestinal and
multi-organ transplants justifies the higher rate (8–25%) of PTLD
incidence while the incidence rate is 1 to 5% in kidney transplants and
liver with lower doses and duration of immunosuppression.
• B-cell proliferation induced by infection with Epstein-Barr virus (EBV)
in the setting of chronic immunosuppression.
• An EBV-associated protein (LMP-1) interacts with host proteins from
the TNF receptor family that leads to cell growth and transformation.
• Yes! These tumours are of host origin but…donor related PTLD is
known to occur in a solid organ transplant. (how is it different?)

5. • B cell proliferation induced
by EBV infection
• Cytotoxic T cells keep EBV-
infected B cells in check.
• Anti T cell Rx or T cell
depletion is therefore a risk
factor for PTLD
• EBV-driven polyclonal
proliferations leading to
EBV(+) or EBV(-) lymphomas
of predominantly, B-cell or
less often T-cell type
Pathogenesis- PTLD

6. Clinical Presentation
• Unexplained fever
• Mononucleosis-like syndrome ( fever, malaise, pharyngitis, tonsillitis)
• Gastrointestinal bleeding, obstruction, or perforation
• Abdominal –mass lesions
• Infiltrative disease of the allograft
• Hepatocellular or pancreatic dysfunction
• Central nervous system disease

7. Diagnosis
• EBV viral load ( high sensitivity, variable specificity)
• Imaging
• Tissue biopsy (excisional node biopsy)
Confirm EBV positivity by immunostaining
oLMP1- latent membrane protein 1
oEBER-EBV encoded RNA
Histological grave
Immunophenotyping (CD20)
Cytogenetics

8. Management
• Therapeutic approaches to PTLD should be based on histology, sites
of disease, and biologic activity.
• Reduction of Immunosuppression
• Antiviral agents (Ganciclovir, Acyclovir, Maribavir) 3) Surgery and
Radiotherapy (localized)
• Rituximab
• Rituximab + Chemotherapy
• EBV Directed cytotoxic T lymphocytes (CTL) – in clinical trials

10. Reduction of Immunosuppression
• Limited disease: a 25% reduction in immunosuppression;
• Extensive disease and critically ill: stop all agents except
• prednisone 7.5–10 mg/d;
• Extensive disease not critically ill: decrease
• ciclosporin/tacrolimus by 50%, discontinue
• azathioprine/mycophenolic- late and maintain prednisone
• 7.5–10 mg/d.
• European guidelines: recommending steroid maintenance
• alone or reducing calcineurin inhibitors e.g, ciclosporin by
• 50% and stopping all other agents e.g. mycophenolate or
• azathioprine.

12. PTLD-EBV
Monitoring
• AT LEAST WEEKLY FOR 3
MONTHS
• FOR ALLO-SCT
• AFTER HIGH RISK SCT
• LONGER MONITORING FOR
- GVHD
- PREVIOUS EBV REACTIVATION
Styczynski et al, BMT 43; 757 (2009)

13. Prevention
• The preventive treatment of LPT consists of avoiding reactivations and
primary infections with EBV. The first is the systematic use of antivirals.
• IV ganciclovir to high-risk pts for a min of 100 days
• Oral acyclovir in low risk patients
• Lower target tacrolimus levels (2-5 ng/mL )

14. Treatment
Reduced immunosuppression – Antivirals – Chemotherapy - Immunotherapy
• The main goal of treatment is healing, also the preservation of the
allografted organ. the heterogeneity of PTLD makes it impossible to
achieve a unified therapeutic approach. However, and since the first
PTLD report, the mainstay of treatment has been RI even with lasting
remissions not at all common.
• Other options like rituximab given in combination or in sequence with
combination chemotherapy, also adoptive immunotherapy, cytokine
therapy and anti-EBV therapy.

15. Conclusion
PTLD represent a significant complication of transplants, the incidence
and presentation of which are constantly evolving, with changes in
immunosuppression protocols.
They are increasingly late and less and less often associated with EBV.
Their care has improved significantly and, thanks to the first
prospective studies, a therapeutic regimen can be proposed,
successively associating BI, rituximab, then rituximab or R-CHOP
according to the answer. PTLD certainly still have a lot of the future ...