Discussion:
Plasmacytoid PTLD is a rare entity in pediatric solid organ transplant patients.2 The first case was described in a teenager with a kidney transplant who presented with EBV-associated post-transplant multiple myeloma.13 The largest case series reported by Perry et al . included five cases in patients after liver and small bowel combined transplant, and these patients responded very well to high dose dexamethasone.7Several subsequent cases were treated successfully with bortezomib, dexamethasone, with or without lenalidomide and autologous stem cell transplant. Most patients remain in remission.8–10,12
Our patient initially responded well to bortezomib and dexamethasone but relapsed with a different presentation of EBV-negative MZL. EBV-negative MZL was recently reported by Galera et al as an unusual form of PTLD.16 Here, the authors presented this as an indolent disease process that could be managed conservatively. Our patient was treated with bendamustine and rituximab as a targeted CD20 therapy, according to the BRISMA/IELSG36 study.18
He relapsed on therapy with plasma cell leukemia with a new t (14;16) (q32;q23) anomaly. This translocation leads to the IgH/MAF fusion gene, a high-risk cytogenetic abnormality occurring in 5% of myeloma patients.19 Plasma cell leukemia is the most aggressive form of plasma cell dyscrasias with very poor prognosis. Treatment is based on myeloma-type regimens. Recently, novel agents have advanced the treatment efficacy of multiple myeloma in adult patients.17,20 The LYRA study showed a 44% partial response rate after 4 cycles with 87% one year progression-free survival.17 Although the peripheral leukemic cells responded to this regimen, he passed away from gastrointestinal hemorrhage secondary to progressive intraabdominal disease. We hypothesize that his intraabdominal pathology may be distinct from his plasma cell leukemia, as he rapidly progressed on a plasma cell targeted regimen.
Our case highlights the heterogenicity of EBV-negative PTLD in pediatric transplant patients, and the evolution of plasma cell neoplasms. The rapid progress of three different forms of PTLD within less than one year is a distinct feature. The literature of pediatric plasmacytoid PTLD is isolated to a few case reports, thus, there is no standard of care. Our case shows that patients with aggressive plasma cell PTLD may respond to a combination of targeted and standard chemotherapy. Further research is needed to understand the pathophysiology of these distinct disease entities.