[Composite lymphoma consisting of adult T-cell leukemia-lymphoma and diffuse large B-cell lymphoma].

A 68-year-old man was admitted to our hospital because of left back pain and systemic lymphadenopathy with hypercalcemia. Serum anti-HTLV-1 antibody was positive. Left cervical lymph node (LN) biopsy revealed proliferation of medium-sized to large CD4-positive atypical cells with modest infiltration of CD20 and Epstein-Barr virus (EBV)-encoded RNA dual-positive atypical large cells. Monoclonal integration of HTLV-1 proviral DNA, plus clonal rearrangement of the T-cell receptor chain gene and the immunoglobulin heavy chain gene, were detected in the same LN specimen. Composite lymphoma consisting of adult T-cell leukemia/lymphoma (ATL) and EBV positive diffuse large B-cell lymphoma (DLBCL) was diagnosed. He was successfully treated with aggressive chemotherapy including rituximab and attained remission. However, eight months later, he developed right shoulder pain due to multiple bone invasions with bilateral cervical lymphadenopathy. Biopsies of a bone lesion and cervical LN revealed recurrence of ATL alone. The patient died despite salvage chemoradiotherapy. These findings suggest that ATL-related immunodeficiency might induce EBV-associated DLBCL.

Comparison of autologous hematopoietic cell transplantation and chemotherapy as postremission treatment in non-M3 acute myeloid leukemia in first complete remission.

UNLABELLED: Randomized trials of acute myeloid leukemia (AML) in first complete remission (CR1) showed that autologous hematopoietic cell transplantation (auto-HCT) improves relapse-free survival (RFS) but not overall survival (OS), compared with chemotherapy. Using a database of 2518 adult patients with AML in CR1, we conducted a 5-month landmark analysis and found that auto-HCT improves 3-year RFS but not OS compared with chemotherapy. INTRODUCTION: A number of randomized trials in patients with AML in CR1 have been conducted and they showed that auto-HCT improves RFS but not OS, compared with chemotherapy. However, because these trials have had compliance problems, the value of auto-HCT still has not been clearly established. PATIENTS AND METHODS: Using a database of 2518 adult patients with AML in CR1, we retrospectively analyzed the outcome of auto-HCT and compared it with intensive nonmyeloablative chemotherapy using landmark analyses. RESULTS: In 103 auto-HCT recipients, OS and RFS at 3 years from treatment were 65% and 57%, respectively. Multivariate analysis showed that unfavorable risk cytogenetics and entry into CR1 after 2 courses of induction treatment predicted a poor outcome. Because the median time interval between CR1 and auto-HCT was 153 days, landmark analyses at 5 months after CR1 were performed to compare 1290 patients who received chemotherapy alone (median age, 52 years; range, 16-70) with 103 who received auto-HCT (median age, 48 years; range, 16-67). Auto-HCT improves 3-year RFS (58% vs. 37%; P < .001) but not OS compared with chemotherapy alone. Among patients with unfavorable risk cytogenetics or those who required 2 courses to reach CR1, there was no significant difference in RFS between the 2 groups. CONCLUSION: Auto-HCT can be considered as a postremission therapy for AML patients with favorable or intermediate risk cytogenetics who achieve CR1 after a single course of induction treatment.

[A case of secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome, complicated with disseminated M. abscessus infection].

A 27-year-old man was admitted to our hospital complaining of a persistent high fever since August 2007. Chest radiography showed infiltration shadows in the right lower lung field. Chest CT revealed scattered small nodular shadows and patchy consolidations in the right lower lobe. He was diagnosed as secondary pulmonary alveolar proteinosis (sPAP) associated with myelodysplastic syndrome (MDS), confirmed by video-assisted thoracic surgery (VATS) and bone marrow aspiration. Sera were negative for anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. He developed a subcutaneous abscess and meningitis caused by M. absessus after VATS. After a long-course of antibiotic therapy, an allogenic peripheral blood stem cell transplantation was performed. But he died of graft versus host disease and M. abscessus sepsis 87 days after transplantation.

[Relapse of autoimmune hemolytic anemia in Evans syndrome after thymectomy for pure red cell aplasia].

A 81-year-old woman was referred to our hospital with pure red cell aplasia (PRCA) associated with a thymoma in May 2005. She had previously suffered from Evans syndrome which had been improved by prednisolone in 1999. She underwent a thymectomy, however her anemia subsequently got worse. Reticulocytopenia was noted and a marrow erythroid series was aplastic. Furthermore, both direct and indirect Coombs tests were positive, and the serum haptoglobin level was low. Based on these findings, the patient was diagnosed as having PRCA complicated with relapsed autoimmune hemolytic anemia (AIHA). The PRCA and AIHA were successfully treated with prednisolone and cyclosporine. To our knowledge, only one case of the PRCA complicated with AIHA after thymectomy has been reported. FoxP3 positive regulatory T-cells (Treg), which maintain immunological self-tolerance, were readily detectable in the excised thymoma. Thus, thymectomy resulted in removal of the Treg pool and might explain the autoimmune activation, believed to be one of the mechanisms of the post-thymectomy recurrence of the AIHA in this case.

Epstein-Barr virus-positive blastoid variant of mantle cell lymphoma in an adult with recurrent infectious mononucleosis-like symptoms: a case report.

Epstein-Barr virus (EBV) is closely associated with several lymphomas, such as Burkitt lymphoma, natural killer/T-cell lymphoma, peripheral T-cell lymphoma, and Hodgkin's lymphoma; however, whether EBV is implicated in mantle cell lymphoma (MCL) has not been established. We report the case of an adult with recurrent infectious mononucleosis (IM)-like symptoms who developed an EBV-positive blastoid variant of MCL. A 54-year-old Japanese man presented with fever, swelling of the oral mucosa and tongue, dispersed pulmonary infiltrations, systemic lymphadenopathy, and splenomegaly. He had a history of recurrent IM-like symptoms (prolonged fever and cervical lymphadenopathy) for at least 1 year. MCL was diagnosed by biopsy of the cervical lymph node. The anti-EBV antibody titer indicated a reactivation of chronic infection with this virus. EBV was detected in most of the lymphoma cells and in the peripheral blood. EBV might have played some role in the tumorigenesis of blastoid MCL.

[A case of chronic myeloid leukemia following TS-1 therapy for advanced gastric cancer].

A 55-year-old woman had received total gastrectomy for advanced gastric cancer in March 2002, and was subsequently treated with adjuvant chemotherapy using oral anti-metabolite TS-1 for 21 months. She was well with no evidence of recurrence of gastric cancer, but leukocytosis was found in June 2005. The analysis of bone marrow revealed that Philadelphia (Ph) chromosome and bcr-abl fusion gene were positive. On the basis of these findings, the chronic phase of secondary chronic myeloid leukemia (CML) was diagnosed. Three months after being started on imatinib therapy, Ph chromosome positive cells disappeared in the bone marrow, and a complete cytogenetic response was achieved. Although CML is rare in secondary leukemia, this is, to our knowledge, the first reported case of therapy-related CML following TS-1 treatment. The present case suggested that imatinib therapy was also effective for secondary CML as well as de novo CML.

Fulminant hemophagocytic syndrome with a high interferon gamma level diagnosed as macrophage activation syndrome.

A 26-year-old woman presented with general fatigue, persistent fever, nuchal lymphadenitis, thrombocytopenia, and liver damage. From the bone marrow finding, we diagnosed her condition as hemophagocytic syndrome. Steroid pulse therapy, cyclosporin A treatment, and combined chemotherapy generated no response. The patient showed severe mucosal bleeding, rapidly experienced multiple organ failure, and finally died of a brain hemorrhage on the 13th hospital day. Epstein-Barr virus, cytomegalovirus, human herpes virus type 6, human parvovirus B19, and herpes simplex virus were not detected. Autopsied samples of the spleen, bone marrow, and liver showed extreme proliferation of activated macrophages, so-called histiocytes, without lymphoid malignancy. The interferon gamma level at presentation was prominently high. The continuously elevated levels of ferritin and soluble interleukin 2 receptor were correlated with the catastrophic outcome. The disease in our case mimicked infantile hemophagocytic lymphohistiocytosis. However, there was neither a family history of the disease nor a mutation in the perforin gene. So, it is reasonable to categorize our case as macrophage activation syndrome. Although our patient lacked arthritis or eruption, we cannot deny the possibility that an oligoarthritis type of systemic-onset juvenile rheumatoid arthritis or, considering the patient's age, adult-onset Still disease lies at the base of our case.

Detection of two cell populations corresponding to distinct maturation stages in API-2/MLT-positive mucosa-associated lymphoid tissue lymphoma cells proliferating in pleural effusion.

A 66-year-old man was admitted to our hospital because of an intra-abdominal tumor and pleural effusion (PE). Immunoelectrophoresis of the serum showed immunoglobulin M (IgM) kappa paraprotein (7330 mg/dL). Abnormal plasmacytoid cells were seen in both the peripheral blood (PB) and the bone marrow (BM). Computed tomography scans showed extensive thickening of the gastric wall and bilateral massive PE without lymph node or pulmonary involvement. A histologic examination of the gastric mucosa showed a diffuse infiltration of small- to medium-sized lymphoid CD20-bearing cells, some of which showed a plasmacytoid morphology. Lymphoepithelial lesions were demonstrated with an immunohistochemical stain. The diagnosis was gastric mucosa-associated lymphoid tissue (MALT) lymphoma infiltrating to the PE, PB, and BM. The PE contained numerous lymphoid cells with plasmacytoid morphology that Southern blotting analysis showed to have a monoclonal IgH gene rearrangement pattern. The cells seemed to be divided into two populations according to their surface markers: mature B-cells (CD19+CD20+CD22+CD21+CD38-) and secretory B-cells (CD19+CD20(dim)CD22-CD21-CD38+). The reverse transcriptase-polymerase chain reaction technique detected the API-2/MLT transcript in the PE and PB. The patient had a good response to fludarabine treatment, which was followed with rituximab therapy. In general, gastric MALT lymphoma cells have a tendency to differentiate into plasma cells. In this article, we show that the cell character of API-2/MLT-positive MALT lymphoma is preserved even when the cells are disseminated. This is the first published case, to our knowledge, in which two differentiation stages of MALT lymphoma cells infiltrating into PE have been confirmed by flow cytometric analysis.

Angioimmunoblastic T-cell lymphoma associated with an antibody to human immunodeficiency virus protein.

A 58-year-old man was admitted with generalized lymphadenopathy. On admission, the patient showed polyclonal hyper-gammopathy in a blood examination, positive results in the direct/indirect Coombs test, and an elevated cold agglutinin titer. Autoimmune thrombocytopenia with a high level of platelet-associated immunoglobulin G complicated the patient's condition. An enzyme immunoassay kit for human immunodeficiency virus (HIV) recombinant proteins p24, gp41, and gp36 showed positive results. Western blot analysis showed the presence of antibodies cross-reacting with HIV p24 gag protein. HIV RNA was not detected by means of a reverse transcriptase-polymerase chain reaction assay, so the patient was not an HIV carrier. Angioimmunoblastic T-cell lymphoma (AILT) was diagnosed on the basis of lymph node biopsy specimens. We speculated that in this case some of the numerous subtypes of polyclonal gamma globulin had coincidentally cross-reacted with HIV p24. Cross-reactive phenomena with HIV in patients with systemic lupus erythematosus have been well investigated, but to our knowledge our patient is the first case of such cross-reactivity involving AILT. Physicians should pay close attention to serologic tests to determine whether the patient truly is a viral carrier.