A malignancy caused by an over immunosuppressed immune system.
It is a rare complication after allogeneic hematopoietic cell transplant and is more likely to occur after solid organ transplantation.
Refers to a spectrum of abnormal lymphoid proliferations, typically of B cells, occurring in the setting of ineffective T-cell function due to immunosuppression after organ transplant.
PTLD represents a spectrum of clinical and morphologic lymphoproliferative states, ranging from benign reactive polyclonal hyperplasia to lymphoma.
Most cases are related to Epstein-Barr virus; it is associated with an EBV infection of donor origin and occurs with the first year after transplantation.
Most cases of PTLD after transplants are associated in the context of an impaired T cell mediated immunity, previously latent EBV infected cells can proliferate and contribute to the pathogenesis of the disease.
Nearly all patients have disease associated with EBV infection, and clinical severity can range from a mononucleosis type illness to fatal rapidly proliferating non-Hodgkin lymphoma.
Post-transplant lymphoproliferative disease is rare after hematopoietic cell transplant, with a total incidence of 1% after 10 years.
The majority of cases occur during the first year after transplant.
The median onset of post transplant lymphoproliferative disease is approximately six months and solid organ transplant and 70-90 days in hematopoietic poetic stem cell transplant.
In stem cell transplant PTLD can occur as early as one week after transplant, with mortality rates near 90%
Prolonged immunosuppression to prevent graft rejection makes patients vulnerable to EBV infections and uncontrolled B cell expansion.
EBV serosostatus are important factors in determining the patient’s risk for developing this process.
The post transplant lymphoproliferative disorder differs from other lymphomas in that it is donor-derived from the unregulated proliferation of the EBV infected B cells in the presence of suppressed T-cell immunity if the transplant.
In immunocompromised individuals, EBV infects and immortalizes B cells and without regulation by active T cells, an unchecked proliferation of EBV positive B cells occurs resulting in malignancy.
Heart-lung and intestinal transplants are associated with the highest risk of developing post-transplant lymphoproliferative disease and renal transplants have the lowest risk, while long, heart, liver, and pancreas transplants are in the middle as far as risk is concerned.
Hematopoietic stem cell transplant patients at high risk are those who receive severe immunosuppressive transplant regimens, with T cell depletion or T-cell depleted donor grafts.
Disease categories related to 4 groups: Early lesions or reactive hyperplasia, polyclonal disease, monoclonal B-cell or T-cell disease, or classic Hodgkin’s lymphoma type disease.
Patients often present with fever, lymphopathy and organ specific manifestations.
Risk factors include the use of ex vivo T cell depletion, the presence of anti-T cell antibodies, the use of umbilical cord blood as a graft source, and the presence of HLA mismatch.
Most common treatment includes reduction in the immunosuppressive therapy, use of rituximab and chemotherapy.
Elevated LDH, multiorgan involvement and organ dysfunction at the time of diagnosis predict for poor prognosis.
Rituximab associated with complete response rate of 35-70%.
Some studies indicate that following EBV levels and giving rituximab when there is a significant titer arise may be a preventative approach.
Chemotherapy is generally reserved for patients with monomorphic disease that is clinically aggressive.