Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation.

A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post-transplantation course was uneventful, except for mild skin acute graft-versus-host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV.

Severe stomatitis and ileocecal perforation developed after all-trans retinoic acid monotherapy in an HLA-B51-positive patient with acute promyelocytic leukemia.

A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behçet's disease. Therefore, hypercytokinemia with DS might have induced Behçet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51.

The Successful Treatment of a Cord Blood Transplant Recipient with Varicella Zoster Virus Meningitis, Radiculitis and Myelitis with Foscarnet.

Infections of the central nervous system (CNS) with varicella zoster virus (VZV) is a rare occurrence after allogeneic hematopoietic stem cell transplantation. We herein report a case of VZV meningitis, radiculitis and myelitis that developed 8 months after cord blood transplantation, shortly after the cessation of cyclosporine and low-dose acyclovir. Although treatment with acyclovir did not achieve a satisfactory response, the patient was successfully treated with foscarnet. Our report indicates that VZV infection should be considered in allo-hematopoietic stem cell transplantation (HSCT) patients with CNS symptoms and that foscarnet may be effective for the treatment of acyclovir-resistant VZV infections of the CNS. The development of optimal prophylactic strategies and vaccination schedules may eradicate post-transplant VZV disease.

Cessation of In-line Filters in Central Venous Catheters Does Not Significantly Influence the Incidence of Bloodstream Infections and Mortality in a Hospital Hematological Ward.

Objective The use of intravenous in-line filters is effective for the mechanical removal of large particles, precipitates, bacteria, fungi, large lipid globules, and air. However, the routine use of in-line filters remains controversial. Many patients with hematological diseases frequently suffer from bloodstream infections (BSIs) with fatal outcomes. Methods The year before cessation of an in-line filter was defined as the "filter period" and the year after its cessation was defined as the "non-filter period." The number of central line-associated bloodstream infections (CLABSIs), which are defined through surveillance, the catheter utilization rate, the number of patient deaths within 7 days after removal of the central venous catheters (CVCs), and the overall survival rate following CVC insertion were measured. Results During both periods, 84 patients had a total of 140 CVCs with a total number of catheter days of 3,407. There were 10 CVCs with CLABSIs, and the overall CLABSI rate was 2.9/1,000 catheter days, including 4 CVCs with CLABSIs (2.5/1,000 catheter days) during the filter period and 6 CVCs with CLABSIs (3.3/1,000 catheter days) during the non-filter period. The CLABSI rate, catheter utilization rate, and mortality did not differ significantly between the two periods. The only independent variable that was found to be significantly associated with the development of CLABSIs was a neutrophil count of <500×10(6)/L (p<0.05). Conclusion Our study revealed that the cessation of in-line filters from CVCs does not significantly influence the incidence of BSIs and mortality in patients with hematological disease. To confirm our results, however, a large-scale randomized controlled study is warranted.

Gradually-Deteriorating Liver Function due to Iron Overload Over Four Years after Allogeneic Stem Cell Transplantation.

In allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients with liver dysfunction, it is often difficult to determine the cause. Several cases of liver dysfunction may be interpreted as chronic graft versus host disease without a definitive diagnosis, resulting in continued immunosuppressive therapy for longer periods. Allo-SCT recipients commonly require frequent red blood cell transfusions during the course of treatment and transplantation, leading to significant iron overload, which could be one of causes of liver dysfunction. Here we report an allo-SCT recipient with chronic deteriorating liver dysfunction due to iron overload, despite maintaining transfusion independence for more than four years. Using magnetic resonance-based liver iron concentration (MR-LIC), iron overload-related liver dysfunction was diagnosed. It drastically improved with monthly phlebotomy and has not recurred following its termination. The observations from our case suggested that iron overload should be recognized as a cause of chronic liver dysfunction even in patients who remain transfusion-independent for several years and that MR-LIC analysis is a useful and reliable method for detecting iron overload and monitoring the effect of iron-reduction therapy.

Primary cerebral lymphomatoid granulomatosis progressing to methotrexate-associated lymphoproliferative disease under immunosuppressive therapy.

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease involving extranodal sites. Although LYG cerebral lesions are usually located adjacent to LYG pulmonary lesions, few reports have described the occurrence of primary cerebral LYG. We herein discuss a case of a 40-year-old Japanese woman with primary cerebral LYG that caused various neurological symptoms for more than five years and progressed to methotrexate-associated lymphoproliferative disease under treatment with immunosuppressive therapy. This case suggests that primary cerebral LYG should be considered a lymphoid neoplasm manifesting as a primary brain tumor and a component of the differential diagnosis of chronic neuroinflammatory disorders.

Early-Onset Severe Diffuse Alveolar Hemorrhage after Bortezomib Administration Suggestive of Pulmonary Involvement of Myeloma Cells.

Severe acute lung injury is a rare but life-threatening complication associated with bortezomib. We report a patient with multiple myeloma who developed a severe diffuse alveolar hemorrhage (DAH) immediately after the first bortezomib administration. The patient was suspected to have pulmonary involvement of myeloma, which caused DAH after rapidly eradicating myeloma cells in the lungs with bortezomib. Rechallenge with bortezomib was performed without recurrent DAH. In patients with multiple myeloma who manifest abnormal pulmonary shadow, we should be aware of early-onset severe DAH after bortezomib administration, which might be due to pulmonary involvement of myeloma cells.

Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutation status.

Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph(+)MPAL) is a rare type of acute leukemia having myeloid and lymphoid features. In the present study, we describe the successful treatment of a 71-year-old Japanese female patient with Ph(+)MPAL by the alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutations. The patient survived in her third complete remission (CR) for over 4 years. In her first CR, the patient was treated with multiple-agent chemotherapy and underwent maintenance therapy with imatinib and monthly vincristine and prednisolone (VP). At the first relapse, an examination of the bone marrow revealed a transformation into acute lymphoblastic leukemia and an F317L mutation in BCR-ABL1 gene, which responded preferentially to nilotinib over dasatinib. She achieved second CR, and nilotinib with VP therapy was selected for maintenance treatment. At second relapse, BCR-ABL1 mutational analysis revealed Y253H mutation instead of F317L mutation, resulting in resistance to nilotinib. The patient achieved third CR with dasatinib and VP therapy, and maintained CR with this treatment. This suggests that appropriate alternation of TKIs may contribute to long-term survival in elderly patients with Ph(+)MPAL.

Successful diagnosis of type II enteropathy-associated T-cell lymphoma using flow cytometry and the cell block technique of celomic fluid manifesting as massive pyoid ascites that could not be diagnosed via emergency laparotomy.

Enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor of intraepithelial T lymphocytes, is a rare and highly aggressive disease. We herein describe a case of type II EATL with massive pyoid ascites in which a histological examination could not be performed despite emergency laparotomy that was successfully diagnosed using flow cytometry and the cell block technique to analyze the celomic fluid. This case suggests that EATL should be included in the differential diagnosis of pyoid ascites of unknown origin and that flow cytometry and the cell block technique of assessing celomic fluid are useful procedures for diagnosing EATL, especially in cases in which conducting a histological examination is impossible.

Secondary neurolymphomatosis detected by whole-body diffusion-weighted magnetic resonance imaging: a case report.

Neurolymphomatosis (NL) is a rare clinical entity defined as peripheral nervous system infiltration by lymphoma. The diagnosis is difficult and often elusive. Whole-body diffusion-weighted magnetic resonance imaging (DW MRI) was developed to enhance the detection of vaguely delineated tumors. Here, we describe the case of a 71-year-old male with secondary NL of diffuse large B-cell lymphoma (DLBCL) that was successfully detected by whole-body DW MRI. The patient was diagnosed with DLBCL extending from the ethmoidal sinus to the nasal cavity, orbital cavity, and anterior cranial fossa. Although he was administered R-THP-COP chemotherapy and the tumor remarkably decreased in size, he developed painful paresthesia and weakness in the left upper and bilateral lower extremities during treatment. Because lymphoma cells were detected in his spinal fluid, high-dose methotrexate (MTX) and weekly intrathecal MTX and cytarabine injections were administered. Test results for lymphoma cells in the spinal fluid became negative ; however, the neurological disorders progressed. Whole-body DW MRI was performed as whole-body screening and could localize NL at the left cervical and bilateral lumbar nerve roots. Both cervical spine plain MRI and enhanced computed tomography performed around the same time could not detect the cervical lesion. Our case report suggests that whole-body DW MRI is a useful diagnostic imaging procedure, especially as whole-body screening in facilities where PET/CT is not available.

Successful treatment by azacitidine therapy of intestinal Behçet's disease associated with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell diseases. It has been reported that several autoimmune diseases are associated with MDS. Recently, the co-occurrence of MDS with trisomy 8 and rare disorders of the immune system, such as Behçet's disease (BD), has been described. Prognosis in the older-onset group of MDS-associated BD is unfavorable. Here, we report a case of MDS-associated intestinal BD treated successfully by azacitidine therapy. A 59-year-old Japanese male suffering from recurrent high fever, melena, and oral and genital ulcerations was diagnosed with MDS with trisomy 8 and intestinal BD by endoscopic and bone marrow examinations. Immunosuppressive therapies, including infliximab, were ineffective. Due to his severe emphysema, the patient was considered ineligible for stem cell transplantation, and azacitidine therapy was initiated. With the exception of fever, the symptoms of intestinal BD improved, and severe malnutrition and anemia were ameliorated. Fluorescence in situ hybridization analyses of the bone marrow before the eighth cycle revealed that the trisomy 8 had not decreased. To our knowledge, this is the first report of azacitidine therapy for MDS-associated BD. We suggest that azacitidine may control intestinal BD by mechanisms other than those responsible for its effect in MDS.

Posterior reversible encephalopathy syndrome in an adult patient with acute lymphoblastic leukemia after remission induction chemotherapy.

Posterior reversible encephalopathy syndrome (PRES) has been reported in childhood leukemia patients increasingly frequently. However, the development of PRES in adult leukemia patients during chemotherapy is very rare. We present a case of PRES in an adult patient with acute lymphoblastic leukemia (ALL) after remission induction chemotherapy. A 28-year-old woman with ALL was administered remission induction chemotherapy consisting of cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase. After initiation of chemotherapy, the patient developed paralytic ileus and hypertension, and on day 30, she suddenly developed generalized convulsions, loss of visual acuity, and muscle weakness in the legs. Magnetic resonance imaging findings and her signs and symptoms were typical of PRES. The symptoms gradually improved following treatment with an anticonvulsant and an antihypertensive agent, and the patient underwent allogeneic bone marrow transplantation. She has completely recovered from PRES and has been asymptomatic without leukemia relapse. During remission induction chemotherapy for ALL, PRES may be caused by multiple drugs, such as L-asparaginase, vincristine, and corticosteroids, with different mechanisms of action. PRES should be recognized as an important complication, which will occur more frequently with the increased intensity of chemotherapy for adult ALL patients.