Posttransplant Lymphoproliferative Disorder

Posttransplant lymphoproliferative disorders (PTLD) are among the most serious complications after organ and cell transplantation, recognized over 30 years ago; questions raised at that time remain incompletely answered.

Common Symptoms

Pulmonary infection; abnormal liver function; poor GI function

Causes and Pathogenesis

(A) Etiology: It is now basically clear that the main causes of PTL are immunosuppression and EBV infection. Although the specific role of individual immunosuppressants is unclear, overall immunosuppression degree is the main determinant; EBV-specific T-cell-mediated immune injury plays a key role. Normally, EBV-infected B cells are controlled by cytotoxic T cells, with B-cell growth/death balanced. Once T-cell function is impaired, balance breaks and PTL develops. In an EBV-infected marrow donor, about 1/1,000,000 B cells are virus-carrying transformed B cells; these are balanced in the healthy donor. However, when T-cell-depleted transplantation is performed to reduce GVHD, residual transformed B cells in the graft escape cytotoxic-T-cell surveillance and proliferate rapidly. Data show simultaneous removal of mature T and B cells from the graft (e.g. soybean-lectin method) markedly reduces EBV-related PTLD after allogeneic BMT. On the other hand, pre-transplant immune destruction in BMT recipients also gives transformed B cells a proliferative opportunity; early post-BMT is the high-risk period. PTLD is more common in children also because this population has a higher pre-transplant EBV-seronegative rate. (B) Pathogenesis: Most posttransplant NHL arises when long-term immunosuppression allows EBV to induce B-cell proliferation. The internal mechanism is now basically clear: an EBV-related protein LMP-1 triggers some members of the host-cell TNF family, causing cell transformation and growth. PTLD has multiple histopathologic patterns: 1. Early lesions: Reactive plasmacytosis and infectious-mononucleosis-like lesions share preservation of some normal architecture (nodal sinuses, tonsillar crypts, residual reactive follicles); the former is characterized by abundant plasma cells with very few immunoblasts, while the latter has typical IM morphology with expanded paracortex and many immunoblasts on a T-cell/plasma-cell background. 2. Polymorphic PTL: normal architecture is completely destroyed, replaced by infiltration of B cells at various differentiation stages. 3. Monomorphic PTL: nodal architecture replaced by sheets of transformed neoplastic cells; cells large with prominent nucleoli and basophilic cytoplasm. Most monomorphic B-cell PTL is DLBCL, mostly immunoblastic variant. Monomorphic T-cell PTL is rare (4%-14%). 4. HL and HL-like PTL: HL-like PTL is always EBV-positive. Classic HL expresses CD15/CD30; HL-like PTL usually expresses B-cell antigens and is almost all EBV-positive.

Treatment

Drug therapy, rehabilitation

Preventive Measures

Since PTL is closely related to immunosuppression degree, prevention mainly reduces excessive immunosuppressants. EBV-specific cytotoxic T cells are used prophylactically in high-risk allogeneic-BMT recipients. Donor-B-cell depletion may also prevent post-BMT EBV-related lymphoma.

Department to Visit

It is recommended to visit the Hematology department; an appointment can be booked on this platform before the visit.

Warm reminder: The above information is for health science reference only and cannot replace professional medical diagnosis. If you have related symptoms, please seek medical attention at a regular hospital promptly.