Just a half century has passed since the discovery of Epstein-Barr virus (EBV). Chronic active EBV infection (CAEBV) is a prototype of EBV-associated T- or NK-cell lymphoproliferative diseases (EBV+T/NK-cell LPDs). The latest guideline for diagnosing CAEBV was proposed by Okano et al (2005). Definitive diagnosis requires evidence of EBV-infected T/NKcell proliferation (practically, evidence of high EBV load and EBV infection to T/NK cells) in the patient. However, the necessary tests are not covered by National Health Insurance, so a more invasive approach (a biopsy of the involved tissue) is needed. Because CAEBV patients possibly experience lethal hypercytokinemia, they should undergo immunochemotherapy followed by multi-drug chemotherapy, and need a preparation of allogeneic hematopoietic stem celltransplantation (HSCT). In cases of insufficient control of the symptoms and a progression of the disease, an allogeneic HSCT might be urgently required. Reduced-intensity conditioning is better than myeloablative conditioning, the overall survival rate is equally > 90% after bone marrow transplantation and cord blood transplantation, and the outcome is not inferior in young adults (<40 years old) compared to that in children.
Natural killer (NK) cells are an important member of the innate immune system. “Missing self” is one of the mechanisms for NK cell response by detection of the loss of self-major histocompatibility complex (MHC) class I expression. This refined mechanism of NK cells, which are believed to have emerged much later than B and T cells based on the evolutional convergence of their variable receptors, rarely trigger autoimmune disorders. After hematopoietic stem cell transplantation (HSCT), donor’s NK cells can recognize the HLA differences between recipient and donor by using killer immunoglobulin-like receptors (KIRs). KIR-mismatched HSCTs have been tried in hope of inducing graft-vs-leukemia effects, with mixed results. The difference in outcomes may be attributable to a number of factors; different diagnoses, HLA-matching, donor source, GVHD prophylaxis, diverse range of KIRs and different NK cell conditions such as inhibiting, activating, licensing and disarming. On the other hand, the dominance of KIR group A haplotype and HLA-C group 1 type in the Japanese population will make it simpler to explore the best recipient-donor combination. This review summarizes our emerging understanding of KIR-HLA diversity, especially in HSCT, to select the optimal donor based on HLA and KIR.
A 4-year-old boy with early relapse of B-cell precursor acute lymphoblastic leukemia of the bone marrow and central nervous system underwent HLA-identical (8/8 serotypes) allogeneic peripheral blood stem cell transplantation from his mother. He developed dry skin on day 102 after transplant and was diagnosed as having chronic graft-versus-host disease. Treatment with prednisolone was initiated. However, he developed sclerodermatous skin changes 1 year after the transplant and scoliosis that progressed with his growth. Nine years after the transplant, the patient developed dyspnea with progressive restrictive lung disease due to restriction of thoracic respiratory motion and hypoventilation resulting from obstruction of the right main bronchus due to progression of scoliosis. Steroid treatment was ineffective, and imatinib was initiated to target his skin lesions. His body surface area was 0.80 m2, and imatinib was initiated at a dose of 100 mg/day for the first 2 weeks, after which the dose was increased to 200 mg/day. Six months after initiating imatinib, improvements were seen in his Rodnan score, which decreased from 36 to 27; in SpO2, which increased from 85% to 95%; and in PCO2, which decreased from 70 mmHg to 50 mmHg. The only adverse reaction was mild diarrhea.