[Exacerbation of autoimmune neutropenia to agranulocytosis in association with severe autoimmune thrombocytopenia and hemolytic anemia in a patient with Sjögren's syndrome].

A 73-year-old woman with Sjögren's syndrome and autoimmune neutropenia (AIN) associated with large granular lymphocytosis of the polyclonal T cell type, demonstrated autoimmune thrombocytopenia (AIT) at diagnosis of sigmoid colon cancer. Ten months later, both AIN and AIT had exacerbated to agranulocytosis and severe thrombocytopenia below 10×10(9)/L, respectively. There were no dysplastic features of bone marrow hematopoietic cells. Furthermore, an in vitro assay of hematopoietic progenitors showed normal granuloid and erythroid colony formation. Although we serially treated her with prednisolone (oral), filgrastim, intravenous high-dose immunoglobulin infusion, cyclophosphamide (oral), danazol, cyclosporine A (oral), and rituximab, number of neutrophils and platelets elevated only temporarily. During the course of agranulocytosis and severe thrombocytopenia, the patient also developed autoimmune hemolytic anemia (AIHA). She died of pneumonia 5 months after the onset of agranulocytosis. This case is very unique and novel in terms of autoimmune phenomena simultaneously directed to granulocytes, platelets, and red blood cells under the background of Sjögren's syndrome.

[Therapeutic efficacy of cyclosporin A for refractory angioimmunoblastic T cell lymphoma].

The prognosis of angioimmunoblastic T cell lymphoma (AITL) is poor because of chemotherapy-resistance and the short duration of remission. In recent years, cyclosporin A (CyA) has been employed as a alternative treatment for AITL in some patients with the rationale that CyA inhibits the activity and proliferation of neoplastic T cells. We herein report 4 chemotherapy-resistant AITL patients who were treated with oral CyA. The dosage of CyA was individually determined in each patient in order to achieve a blood CyA concentration of around 200 ng/ml at the trough level. A patient in whom AITL had relapsed 3 months after high dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) achieved a sustained complete remission (CR) with CyA and underwent allogeneic HSCT. In 2 patients who had failed to respond to conventional chemotherapies, the circulating lymphoma cells rapidly disappeared after the initiation of CyA, and one of these patients demonstrated a durable CR. The other patient showed a good response to CyA, but the agent was discontinued because of infection. The remaining one patient with advanced AITL did not respond to CyA and died of disease progression. To our knowledge, the efficacy of CyA for chemotherapy-resistant AITL, even in a leukemic state, has not previously been reported.

Systemic follicular lymphoma with massive intestinal involvement with leukemic manifestation.

A 30-year-old man was referred to our hospital with leukocytosis and fecal occult blood. His white blood cell count was 30.2 × 10(9)/L with 79% small- to medium-sized lymphocytes. Surface antigen analysis revealed that these lymphocytes were positive for CD19, CD20, CD10, and CD23, but negative for CD5. The lymphocytes infiltrated the bone marrow. On endoscopic examination of the duodenum and jejunum, many small polypoid lesions were observed. A histologic picture of a biopsied lesion showed diffuse infiltration of small- to medium-sized lymphocytes in the submucosal region. On immunohistochemistry, these lymphocytes were positive for CD20, BCL2, and CD10 (weakly). Polymerase chain reaction analysis of cells from peripheral blood, bone marrow, and intestinal lesion showed a fusion product of BCL2 and immunoglobulin heavy chain (IGH) genes. The fused BCL2/IGH gene was also demonstrated by fluorescence in situ hybridization in the same cell sources. Computed tomography scanning showed marked wall thickening throughout the small intestine and enlarged mesenteric lymph nodes. A diagnosis of follicular lymphoma with massive intestinal involvement in a leukemic state was made. After 6 courses of rituximab-combined CHOP chemotherapy, complete remission was obtained.

Histiocytic sarcoma and underlying chronic myelomonocytic leukemia: a proposal for the developmental classification of histiocytic sarcoma.

A 70-year-old male was admitted because of back pain due to peri-vertebral tumors. The histologic picture of a needle-biopsied tumor specimen showed pleomorphic large cell infiltration into the collagen fibers. On immunohistochemistry, these abnormal cells were positive for CD68, CD163 and lysozyme but negative for CD1a, 21, 30, and S100. Flow cytometric analysis also demonstrated that these cells were positive for CD13, 14, 38, 45, 56, and HLA-DR. A bone marrow aspirate showed the marked infiltration of abnormal large cells with the same surface antigens as described above. A diagnosis of HS was made. He showed monocytosis in the peripheral blood of more than 1.0 x 10(9)/L from presentation. The karyotype of bone marrow cells was 46,XY,+8. Fluorescent in situ hybridization (FISH) analysis with a probe for chromosome no. 8 showed that all these monocytes carried +8, indicating that he had another disorder of chronic myelomonocytic leukemia (CMML). FISH analysis with a probe for chromosome no. 12 demonstrated that the abnormal large cells in the bone marrow were all tetraploid, while analysis with the chromosome no. 8 probe showed more than 8 signals per cell, indicating that HS cells carried octasomy to decasomy of chromosome no. 8. These findings strongly suggest that HS in the present patient originated from underlying CMML.