ITP or Not-ITP - a Rare Case of PTLD Recurrence Presenting As Autoimmune Thrombocytopenia

Introduction:

Post-transplant lymphoprolifeative disorder (PTLD) is a heterogeneous group of lymphoproliferative disorders of lymphoid and/or plasmacytic differentiation that range from hyperplasias to aggressive non-hodgkin's lymphoma. It occurs in the setting of iatrogenic immunosuppression and usually EBV infection after solid organ or hematopoietic stem cell transplantation. PTLD can assume an astonishing number of guises and can often presents with fatigue, fever, weight loss to common hematologic disorders such as anemia and thrombocytopenia. PTLDs have been known to give rise to autoimmune hematologic disorders such as AIHA but it is extremely rare to see autoimmune thrombocytopenia as the presenting clinical sign.

Case:

A 46 year old male who underwent OLT for history of primary sclerosing cholangitis in 2007 and received graft rejection prevention with Tacrolimus. In 2008, he developed EBV positive PTLD while on immunosuppression, which was successfully treated with reducing to half dose and administration of three doses of Rituximab. Since resolution of PTLD, he was maintained on Tacrolimus up until current presentation.

Patient presented to the hospital in July 2016 with mild gingival bleeding and platelet count of 4,000 cells/ml. Presuming a diagnosis of idiopathic thrombocytopenic purpura (ITP), he was started on prednisone 1mg/kg/day, was given two doses each of IVIG and RhoGam, as well as platelet transfusions with a goal of >10K. His thrombocytopenia remained non-responsive to aforementioned therapies, prompting further evaluation for a lymphoproliferative disorder. The bone marrow biopsy showed no evidence of clonal proliferation or dysplastic cells but increased megakaryocytes. However, a CT scan showed right axillary, subpectoral, and periaortic lymphadenopathy as well as a splenic mass. An excisional biopsy of the right axillary node revealed B-cell neoplasm, EBV negative, weakly CD20+ with focal plasmacytoma-like features, consistent with PTLD. Subsequently, we held Tacrolimus immunosuppression while closely monitoring hepatic function.

He was started on weekly rituximab infusions, with a plan to evaluate his response before considering chemoimmunotherapy with CHOP. We opted not to pursue adding CHOP therapy upfront due to severe thrombocytopenia and risk of further myelosuppression. The patient's platelet count remained at 5,000-7,000 cells/ml until the end of week 2 of rituximab treatment. He was then discharged home on hospital day 20 with a platelet count of 58. As an outpatient, he continued to receive weekly Rituximab for a total of 4 doses and his platelet count eventually improved to 246,000 cells/ml.

Discussion:

PTLD is now the most common malignancy complicating solid organ transplantation (excluding nonmelanoma skin cancer and in situ cervical cancer). The majority of PTLD cases are secondary to EBV primary infection/reactivation which present early (within 1 year of transplant) but up to 33% to 48% cases are EBV negative, which usually present late in the course. The presenting symptom is highly variable, and it is imperative to differentiate between autoimmune thrombocytopenia due to PTLD vs idiopathic origin, as this determines the appropriate treatment strategy. In our patient, the cause of thrombocytopenia is likely due to a paraneoplastic process secondary to underlying PTLD. He did not have any significant response with steroids or IVIG, which is the conventional treatment for ITP, but instead showed clinical improvement with reduction in immunosuppression (RIS) and the anti-CD20 monoclonal antibody rituximab.

Successful treatment of autoimmune thrombocytopenia secondary to PTLD involves early diagnosis and prompt institution of appropriate treatment. The treatment for PTLD lacks a standardized therapeutic approach with multiple treatment modalities. Despite the pathologic diversity, RIS remains the cornerstone of the treatment. Additional treatment with immunotherapy with rituximab has shown up to 50% response rates in CD20+ PTLDs. Systemic chemoimmunotherapy with R-CHOP is also considered in patients who are highly symptomatic and can tolerate chemotherapy.

As displayed in the case of our patient, PTLD presents a multifaceted challenge in diagnosis and treatment. Early recognition of autoimmune thrombocytopenia secondary to PTLD is critical in rendering appropriate therapeutic intervention.