Antibcell Therapy

There are numerous reports that support the effectiveness of anti-B-cell therapy for the treatment of PTLD in both SOT and HSCT patients.38 39 Benkerrou et al.40 reported the outcome of 58 patients after SOT or HSCT with EBV-PTLD who were treated with anti-CD21 plus anti-CD24 antibodies: 61% of patients achieved a CR, with a 1-year overall survival of 46% (compared with 29% in historical controls). Several recent reports have demonstrated a benefit from the use of rituximab, a humanized monoclonal IgG1 kappa antibody against the CD20 antigen found on the surface of malignant and normal B cells, but not on other normal tissues. It has been found to mediate complement-dependent cell lysis and antibody-dependent cellular cytotoxicity.41 Milpied et al. reported the outcome of 32 transplant recipients with PTLD who were treated with rituximab: response (CR + PR) was seen in 65% of SOT and 83% of HSCT recipients, with 73% surviving at 1 year.42 Ganne et al. reported the outcome of eight cases of PTLD occurring after SOT. Complete remission was achieved in seven patients, and seven patients maintained functioning grafts.43 Rituximab is often used as first-line therapy in patients with PTLD occurring after HSCT and as second-line therapy after failure of reduction in immuno-suppression in SOT recipients.

Rituximab has also been used in the preemptive setting for the prevention of PTLD in high-risk patients. van Esser et al.44 evaluated EBV reactivation by PCR viral load testing in patients undergoing allogeneic HSCT. They found that patients undergoing a T-cell depleted allogeneic HSCT were at high risk for PTLD if the plasma EBV viral load exceeded 1000 genome equivalents/milliliter (gEq/mL). Although the negative predictive value of viral load testing was 100%, the positive predictive value was only 39%, indicating that many patients were still able to mount an effective immune response and clear the viral reactivation. They suggested that monitoring the reconstitution of EBV-specific T lymphocytes may add to the predictive value of the viral load by PCR; such assays are now available and include the enumeration of EBV-specific

Figure 62.9 Pulmonary nodule

T cells by tetramer binding or by the induction of intracellular interferon -gamma (IFN-y) in T cells after specific stimulation.44 In order to evaluate the prevention of EBV-PTLD by preemptive use of rituximab, van Esser et al.9 evaluated 49 recipients of a TCD allogeneic HSCT by performing EBV viral load by PCR. Preemptive therapy with a single infusion of rituximab was given to 15 patients with an EBV viral load of 1000 gEq/mL or more. A total of 14 patients demonstrated a complete response, as defined by prevention of EBV-PTLD and complete clearance of EBV-DNA from the plasma, which was achieved after a median of 8 days.

Figure 62.10 Neck adenopathy

They compared this outcome with their historical cohort with the same high-risk features and showed a reduction of PTLD incidence from 49 to 18% and reduction in PTLD mortality from 26 to 0%.9 However, not all B-cell PTLD express CD20. Kaleem et al. found that 16% of the PTLD cases they evaluated by flow cytometry showed almost complete lack of CD20 expression and several other cases showed partial and dim expression on CD20.45

Finally, analysis of patients with PTLD in remission after chemotherapy or withdrawal of immunosuppres-sion has confirmed a relationship between disease activity and EBV viral load by PCR. However, Yang et al. suggest that this correlation may not exist in patients treated with rituximab. They note that EBV-infected lymphocytes in the peripheral blood differ in their sensitivity to rituximab from tumor cells of PTLD; that is, EBV-infected cells in the peripheral blood rapidly decline with therapy, whereas the response of tumor cells is variable. They caution that monitoring viral load in peripheral blood may not predict clinical response in patients with PTLD treated with rituximab.46

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