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Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening disease characterized by the uncontrolled proliferation of EBV-infected T/NK cells with resultant immune system failure against EBV. While a CD5−HLA-DR+CD8+ T-cell population was previously shown to be EBV-infected cells and a useful marker for monitoring the response to treatment of EBV-HLH, changes in other lymphocyte subsets associated with EBV-HLH treatments have not been closely studied. We herein report a 25-year-old woman with EBV-HLH who presented with a fever, liver failure, and pancytopenia. CD8+ T cells harbored EBV. After failing steroid pulse therapy, one course of CHOP therapy immediately improved her fever and laboratory data and reduced the population of EBV-infected cells. Although the number of EBV-infected cells increased on day 20 of CHOP, a sharp increase in NK cells and normal activated T cells ensued, and the infected cells disappeared without an additional CHOP cycle. She has maintained remission without complications. This rapid immune reconstitution has not been observed in two other patients treated with HLH-2004 protocol-like regimens including prolonged immunosuppressants and etoposide. One cycle of CHOP was thought to have induced the resolution of EBV-HLH by eliminating infected cells as well as inducing the reconstruction of anti-EBV immunity.

Although increased blood cell deficiency of glycosyl phosphatidylinositol-anchored membrane proteins has often been detected in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), the clinical significance of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells remains to be elucidated. We established a sensitive flow cytometric assay capable of detecting less than 0.01% of CD59-CD55- blood cells in a sample and used the assay to examine a large number of patients with bone marrow failure. An increase in the proportion of PNH-type cells was detectable in approximately 60% of all AA patients and in 20% of all refractory anemia (RA)-MDS patients. The increase was undetectable in patients with RA with an excessive number of blasts, acute myelogenous leukemia, multiple myeloma, or systemic lupus erythematosus. Our study showed that the presence of an increased number of PNH-type cells was predictive of a good response to immunosuppressive therapy and a favorable prognosis among patients with recently diagnosed AA and RA. A sensitive flow cytometric analysis for detection of a small population of PNH-type cells in peripheral blood cells is one of the most important examinations in the management of bone marrow failure.

Acquired aplastic anemia (AA) is considered an immune-mediated disease because approximately 70% of AA patients improve with immunosuppressive therapy. However, little is known about the inciting antigens or the mechanisms responsible for the destruction of hematopoietic stem cells by immune system attack. Recent advances in immunologic techniques have promoted our understanding of the pathogenesis of AA and have provided evidence that AA is an organ-specific T-cell-mediated disease localized in the bone marrow. Moreover, antibody screening of patients' serum with a complementary DNA library derived from hematopoietic cells has identified several proteins as candidate autoantigens in AA.

Some patients with hairy cell leukemia (HCL) manifest pancytopenia and bone marrow hypoplasia without an apparent increase in atypical cells, so their disease resembles severe aplastic anemia at onset. We treated 2 HCL patients, who were initially diagnosed with aplastic anemia, with antithymocyte globulin (ATG) in combination with cyclosporine or antilymphocyte globulin (ALG). Both patients obtained partial remission in response to the immunosuppressive therapy and did not need transfusion treatment for more than 3 years. Sustained improvement of hematopoiesis in such B-cell malignancies after ATG/ ALG therapy suggests that the mechanisms underlying successful immunosuppressive therapy for aplastic anemia may involve B-cell suppression, inhibiting hematopoietic stem cells.

Patients with severe infections are thought to be ineligible for cord blood stem cell transplantation (CBT) because the conventional 5-6 day-conditioning regimens potentially makes them susceptible to fatal infections by the time neutrophil engraftment occurs. Two patients were treated with minimum conditioning regimens consisting of 30 mg/m(2) fludarabin (Flu) and 2 g/m(2) cyclophosphamide (CY) on day-1 and total body irradiation (TBI) of 2 or 4 Gy on day -1 or 0 followed by single unit CBT. The reasons for adopting such weak regimen were febrile neutropenia due to the rejection of the first cord blood (CB) graft given to a patient with follicular lymphoma resistant to chemotherapy and pulmonary aspergillosis in another patient with AML who relapsed after CBT. The AML patient received 40 mg/m(2) of melphalan on day-2 to reduce the leukemia burden. Both patients achieved 100% donor chimerism by day 19 and day 20 after CBT without an apparent exacerbation of the infections and remained in remission at 23 and 18 months after the CBT. These findings suggest that the 1-2 day regimens excluding antihuman thymocyte globulin may be sufficiently potent to ensure engraftment of CB in immunocompromised patients and safely administered even when patients are complicated by active infections.

Although cyclosporine (CsA) is a key drug in the treatment of acquired aplastic anemia (AA), the role of single-agent therapy with CsA remains unclear. To determine the efficacy of CsA in the treatment of AA, we treated 38 AA patients with CsA alone and followed up the patients for 6 months to 16 years. Twenty patients (53%) achieved either a partial or complete remission within 1 year of starting CsA therapy. Thirteen (81%) of 16 patients who showed an increase in the reticulocyte count of >20 x 109/L within 2 months achieved remission, whereas the response rate was only 32% in patients who failed to show such an increase in the reticulocyte count. The actuarial overall survival and failure-free survival rates at 5 years were 91% and 37%, respectively. These data indicate that CsA alone can achieve a sustained remission in approximately 40% of AA patients, with a low probability of inducing secondary clonal diseases. Given its low toxicity and because the effectiveness of CsA can be judged within 2 months of therapy, CsA may be the first drug of choice at outpatient clinics for AA patients not requiring transfusions.

We describe a 35-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic sibling donor peripheral blood stem cell transplantation (PBSCT) and entered a second complete remission. Upon detection of BCR-ABL transcripts after PBSCT, the patient received imatinib, leading to molecular remission. Following the failure of donor leukocyte infusions, she underwent reduced-intensity unrelated cord blood transplantation (RI-UCBT), and has continued durable molecular remission for more than 30 months without substantial graft-versus-host disease. Because of a lack of adverse effects of imatinib on transplantation outcome, a treatment strategy consisting of molecular monitoring-guided initiation of imatinib followed by RI-UCBT may be promising in the management of Ph+ ALL after allogeneic SCT.