Reduction Of Immunosuppression Surgery Radiation Therapy

Decreasing immunosuppressive therapy is often the first step taken in the management of PTLD in the SOT setting and has proven to be efficacious in small case series reports, with response rates ranging from 23 to 89%. Tsai et al. reported one of the largest series on the outcome of 42 adult organ transplant recipients who developed PTLD and were treated with reduction in immunosuppression with or without surgical resection of all known disease: 73.8% achieved a complete remission. Of those patients who were treated with reduction in immunosuppression alone, 63% responded, with a median time to documented response of 3.6 weeks. They noted that an elevated LDH ratio, organ dysfunction, and multiorgan involvement by PTLD predicted for lack of response to reduction in immunosuppression. In patients with none of these risk factors, 89% responded to reduction in immunosuppression, while 60% with 1 risk factor responded and 0 % with 2-3 risk factors responded. However, such a maneuver is associated with the risk

Table 62.5 Management of PTLD

Monitor EBV-DNA viral load by PCR in cell-free plasma once every 1-2 weeks in high-risk transplant patients.

When EBV reactivation occurs, screen patients for signs and symptoms of early PTLD.

Obtain histologic confirmation of PTLD and perform staging studies to document extent of disease. This includes serum LDH, CT/PET scans, and bilateral bone marrow aspirate and biopsy.

Reduce immunosuppressive therapy as tolerated by SOT or HSCT recipient.

Consider surgery or radiation therapy for localized disease.

Patients who fail to respond to reduction in immunosuppression should be considered for therapy with rituximab if CD20 expression documented.

Patients who fail to respond to rituximab or who are not candidates for such therapy should be considered for cytotoxic chemotherapy. Patients with stage IV disease and those with an elevated LDH may be considered for initial combination therapy with both chemotherapy and rituximab.

If available, HSCT patients can be considered for adoptive immunotherapy with donor T-cells.

SOT: Solid eagar transplant; EBV: Epstein-Barr virus; PTLD: past-transplant lymphoproliferative disorder; LDH: Grent lactate dehydrogenase; HSCT: Remotopoietic stem cell transplant.

of allograft rejection, which can be fatal in setting of heart, liver, or lung transplantation. In this study, almost all cases of acute rejection could be treated by increasing immunosuppression without compromising the initial effect of immunosuppresion on reduction of the PTLD. Tsai et al. noted that the high response rate and low rejection rate in this study suggests that one can often find a level of immunosuppression sufficient for PTLD resolution while simultaneously protecting the allograft in many patients.37 Liver, pancreas, and kidney transplant patients are often treated with complete cessation of all immuno-suppression, except for a maintenance dose of steroids to prevent an adrenal crisis, as acute rejection can be quickly identified noninvasively by following liver enzymes and serum creatinine. Severe rejection can then be aborted with reinstitution of immunosuppre-

Table 62.6 Poor prognostic features Monomorphic subtype with high state High LDH

Multivisceral disease (4 or more sites) CNS involvement HSCT vs SOT

LDH: lactate dehydrogenase; HSCT: Renatopoictic stem cell transplant; SOT: solid organ transplant.

sion and rescue of the graft. In contrast, for heart and lung transplant recipients, immunosuppression is reduced but not stopped completely. For example, drugs such as azathioprine and mycophenolate mofetil are discontinued, while drugs such as steroids, cyclosporine, or tacrolimus are maintained at a reduced dose. Patients not responding with a CR (Complete Remission) or PR (Partial Remission) by 4 weeks should be evaluated for additional therapies. Radiation therapy applied to localized PTLD may also be curative.

Unfortunately, HSCT recipients rarely benefit from a decrease in immunosuppressive therapy as endogenous immune recovery posttransplant may take several weeks to months.

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