Intraventricular rituximab and systemic chemotherapy for treatment of central nervous system post‐transplant lymphoproliferative disorder after kidney transplantation

Abstract

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominantly monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard.

Central nervous system EBV lymphoproliferative disorder in a patient with rhabdomyosarcoma

“…Although rituximab is one of the most promising treatments for EBV‐LPD, it does not penetrate the BBB effectively. Recently, rituximab has been used as high‐dose or intrathecal therapy for the treatment of CNS‐LPD . The combination of the standard rituximab dose schedule and HD‐MTX, however, may be effective initially for treating isolated CNS‐LPD .…”

“…Recently, rituximab has been used as high‐dose or intrathecal therapy for the treatment of CNS‐LPD . The combination of the standard rituximab dose schedule and HD‐MTX, however, may be effective initially for treating isolated CNS‐LPD . We eventually used the combination of HD‐MTX and rituximab for EBV‐LPD, which enabled the successful treatment of both CNS and systemic disease.…”

Acute antibody‐mediated rejection in pediatric kidney transplants: A single center experience

“…Rituximab was initially approved for use as a treatment of lymphomas and is also used in the treatment for post‐transplant lymphoproliferative disease and recurrent focal segmental glomerulosclerosis. Case reports of rituximab use in the treatment of aAMR are coming out with varying degrees of success , .…”

“…Another case report showed that combination therapy with steroid pulses, IVIgG, PP, and rituximab is potentially effective in the treatment of aAMR in children . Unfortunately, rituximab use was not shown to have a significant effect on antibody intensity , and this is concerning as failure to significantly reduce or remove the antibodies can lead to chronic allograft injury.…”

Infections in Pediatric Kidney Transplant Recipients

“…While debate remains as to which method provides the optimal site of amplification, [33][34][35] the specificity and positive predictive value of any method of measuring EBV PCR in blood in predicting PTLD remains low, and case reports have shown that viral load monitoring alone in these children does not always help predict when a chronic high viral load patient will develop PTLD, since not all patients with EBV viremia develop PTLD. 36 There is no consensus on what viral load should prompt intervention, and because PCR techniques can differ between institutions, results cannot be generalized. Most clinicians agree that the first line of therapy for transplant recipients with an increasing EBV load is the reduction of immunosuppressive medications with the recommendation that patients with PTLD have more significant reduction or cessation of immunosuppressive medications.…”