Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide for systemic Epstein-Barr virus-positive T-cell lymphoma of childhood

Abstract

Epstein-Barr virus-positive T-cell and NK-cell lymphoproliferative diseases (EBV-T/NK-LPD) is categorized into two major groups: systemic Epstein-Barr virus-positive T-cell lymphoma of childhood (SETL) and chronic active EBV infection (CAEBV) [1]. SETL is characterized by clonal proliferation of EBV-infected T cells with an activated cytotoxic phenotype, which develops in children and young adults subsequent to primary acute EBV infection or during the course of CAEBV. Since SETL becomes lifethreatening within days to weeks due to hemophagocytosis and multiple organ failure, immediate treatment is often given priority over a confirmed diagnosis [2]. Chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for EBV-T/NK-LPD, regardless of disease category [3]. Due to the rapid progressive nature of the disease, reports of allo-HSCT for SETL are extremely rare: we could find only one case report of a successful HLA-mismatched sibling donor transplantation using myeloablative conditioning (MAC) [4]. Generally, allo-HSCT for SETL is carried out by reference to that for CAEBV. Here, we describe successful haploidentical allo-HSCT using posttransplant cyclophosphamide (PTCy) and a reduced intensity conditioning (RIC) regimen in a 16-yearold woman with SETL. A 16-year-old Japanese woman presented with a history of fever and sore throat over several weeks. Neither she nor her family had a history of recurrent infectious disease suggesting an immunodeficiency disorder. On admission, she was alert and oriented, with a temperature was 40 °C, a pulse of 122 beats per min, blood pressure at 112/60 mmHg, respiratory rate at 40 breaths per min, and oxygen saturation at 100% on ambient air. Physical examination revealed bilateral posterior cervical lymphadenopathy and hepatosplenomegaly. A Complete blood count showed the following: white blood cells, 2500/μl (metamyelocytes, 2%; band, 20.5%; segmented, 36.5%; lymphocytes, 33%; monocytes, 2.0%; abnormal lymphoid cells, 6%); hemoglobin, 14.0 g/dl; and platelets, 23,000/μl. Other laboratory tests showed acute liver dysfunction (total bilirubin, 4.3 mg/ dl; aspartate transaminase, 130 U/l; alanine aminotransferase, 106 U/l; lactate dehydrogenase, 966 U/l; alkaline phosphatase, 718 U/l; γ-glutamyl transpeptidase 224 U/l) and metabolic acidosis with respiratory compensation. Serum soluble interleukin-2 receptor (sIL2-R, 47534 U/ml) and ferritin (5149 ng/ml) were elevated markedly, but not fasting triglycerides (177 mg/dl) or fibrinogen (183 mg/dl). EBV antibody tests showed a primary infection pattern: EBV-viral capsid antigen antibody (VCA) IgM, ×10; EBVVCA IgG, ×160; EBV nuclear antigen <×10; EBV-early antigen (EA) IgA, <×10; and EA IgG, <×10. The EBVDNA level in peripheral whole blood was 3.1 × 10 copies/ ml. The bone marrow smear revealed 30% abnormal lymphoid cells without hemophagocytosis. These cells were characterized as follows: CD2+, CD3+, CD4−, CD5−, CD7+, CD8+, CD25+, CD26+, CD38+, CD56−, HLADR+. The clonal gene rearrangement of T-cell β chain receptors was positive. G banding analysis showed a normal karyotype. Bone marrow biopsy showed infiltration by * Satoshi Yoshioka [email protected]