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A 68-year-old man was admitted for bleeding tendency and generalized lymphadenopathy. A diagnosis of idiopathic thrombocytopenic purpura (ITP) associated with mantle cell lymphoma was made. The anti-CD20 monoclonal antibody rituximab 375 mg/m2 was given intravenously once weekly for four consecutive weeks. The patient's platelet counts increased gradually from 0.6 x 10(4)/microliter to 5.8 x 10(4)/microliter. At eighteen weeks after discontinuation of rituximab medication, his platelet count increased again to 10. 3 x 10(4)/microliter and this value has been sustained up to the time of writing. This suggests that rituximab is useful in the treatment of ITP associated with malignant lymphoma.

The physical signs of tissue iron deficiency include smooth and red tongue, angular stomatitis, koilonychia, and pica. The incidence of these conditions is unknown in Japan. We evaluated the frequency and development of tissue iron deficiency in 353 patients with iron deficiency anemia. The frequency of tissue iron deficiency was 6.8%; papillary atrophy of the tongue, 5.4%; abnormal nails, 5.4%; angular stomatitis, 1.1%; Plummer-Vinson syndrome, 1.7%; and pica, 0.06%. These findings were compared with the date collected by Wintrobe and Beveridge. The development and incidence of tissue iron deficiency correlated significantly with the severity of iron deficiency anemia.

A 38 year old woman with paroxysmal nocturnal hemoglobinuria was admitted to our hospital because of hemoptysis. Pulmonary infarction was diagnosed by the perfusion lung scan. In spite of the administration of prednisolone, dextran, low molecular weight heparin, and warfarin, she died of pulmonary infarction and secondary pulmonary hypertension. Autopsy revealed thromboembolism of both pulmonary arteries and hepatic central vein thrombosis. Recent understanding of the pathogenesis and incidence of thromboembolism in paroxysmal nocturnal hemoglobinuria was discussed.

A 26-year-old woman was admitted to our hospital for lumbago on November 29, 1995. The white blood cell count was 6,500/microliter with 26.5% myeloblasts and the bone marrow was hyperplastic due to myeloblasts. Myeloblasts were negative for myeloperoxidase and positive for alpha-naphthyl butylate esterase, CD11a (89%), CD11b (38%), CD11c (92%), CD33 (91%) and HLA-DR (58%). Chromosomal abnormalities were recognized: 46, XX, t(9;11) (p22;q23), 45, XX, -7, t(9;11) (p22;q23) and 47, XX, +19, t(9;11) (p22;q23). Acute myeloblastic leukemia (M5a) was diagnosed. Disseminated intravascular coagulation was also present. The patient received induction therapy and achieved remission on January 9, 1996, but myeloblasts increased to 3.6% in bone marrow despite consolidation therapy. Low doses of cytarabine (AraC) and etoposide were instituted on March 7, granulocyte colony-stimulating factor (G-CSF) was started on March 15, and pronounced skin infiltration developed on March 18. The patient received reinduction therapy from April 16 and administration of G-CSF was combined for 2 days, and a marked increment of myeloblasts in the peripheral blood was observed. After discontinuation of G-CSF, myeloblasts decreased and skin infiltration disappeared. However, the patient died of cerebral infiltration on June 30. The response of myeloblasts to G-CSF by in vitro liquid culture was noteworthy. The present case stresses the requirement for great caution to be exercised in the use of G-CSF in patients receiving low dose AraC.

A 34-year-old man was admitted to our hospital for a headache in March, 1995. The patient's hemoglobin was 7.5 g/dl, platelet count was 1.8 x 10(4)/microliter and white blood cell (WBC) count was 12,400/microliters with 99% myeloblasts. Myeloblasts were agranular or hypogranular but electron microscopy revealed microgranules in cytoplasm, and a few faggots were observed. The bone marrow was hyperplastic due to myeloblasts and chromosomal abnormality was recognized: 46, XY, t(15; 17) (q22; q12). PML-RAR alpha with intron 3 breakpoint of the PML locus, and rearrangements of the T-cell receptor beta and gamma genes were detected. These cells were positive for CD2 (63%), CD8 (47%), CD13 (87%) and CD33 (99%). Microgranular variant type of acute promyelocytic leukemia (APL) was diagnosed. Disseminated intravascular coagulation (DIC) was also present. The patient was treated with enocitabine, daunorubicin, 6-mercaptopurine, dalteparin sodium, anti-thrombin III concentrates and gabexate mesilate with prophylactic frozen transfusions of fresh plasma and platelet transfusions for 5 days, but WBC count did not decrease and DIC did not improve. The patient died of cerebral hemorrhage 7 days after diagnosis of APL. APL with CD8 expression has never been reported. We suggest that therapy should be modified in this type of APL and conclusions concerning the most appropriate therapeutic strategy will depend on the results of treatment of similar cases in the future.

Concerning parenteral iron therapy in iron deficiency anemia, Nakao's formula has been used to calculate the total amount of iron to be given, based on 80 ml/kg of circulating blood volume and 17 mg/kg of storage iron in healthy Japanese. Recent studies using radionuclide and radioimmunoassay revealed 65 ml/kg as the circulating blood volume and 500 mg as storage iron. From these data, the total amount of iron can be calculated from the following formula; 3.4 (16-X) x 65 x body weigh/100 + 500 mg (B) where 3.4 is the conversion factor for grams of hemoglobin to mg iron and X is the hemoglobin value before treatment. Parenteral iron therapy was performed in 15 patients with iron deficiency anemia using a total dose of iron calculated by the above the formula (B). The results were effective, and no decrease of hemoglobin was seen except in cases with continuous bleeding. In such cases, iron doses depending upon the amount of continuous bleeding should be added to the total amounts obtained from formula (B).

A 56-year-old woman developed mixed warm and cold antibody type autoimmune hemolytic anemia (mixed AIHA) associated with systemic lupus erythematosus. The patient was admitted to our hospital for acrocyanosis and shortness of breath. High fever and jaundice were observed. Urinalysis revealed protein and hemoglobin, and the sediment contained granular and hyaline casts. Her erythrocytes agglutinated markedly at room temperature. Her hemoglobin was 5.6 g/dl and reticulocyts were 19.3%. Total bilirubin, GOT and LDH were elevated, while haptoglobin and complements were abnormally reduced. Polyclonal increase of immunoglobulin, ANA and anti-Sm antibody were detected. The direct antiglobulin test was positive; IgG1, IgG3 and C3d were detected on the red cell surface. The cold agglutinin (CA) titer was 4096, showing anti-I blood group specificity, and was still active at 30 degrees C. Upon administration of prednisolone gradual increase of hemoglobin and decrease of reticulocytes were observed, indicating the healing of hemolysis. CA disappeared but the direct antiglobulin test remained positive. Mixed AIHA has been defined as the presence of both warm and cold antibodies. In addition, the presence of symptoms of cold agglutinin disease, or low-titer and high thermal amplitude CA might be necessary for the diagnosis of mixed AIHA.

We describe a 69-year-old man who developed chylothorax after a 9-year remission of malignant lymphoma. The patient was admitted to our hospital and received exploratory laparotomy for ileus in February 1986. Bulky masses in the posterior mediastinum and the retroperitoneum, and also a jejunal tumor were observed. Fibrosis of the liver was also observed. The jejunal tumor was removed and histological findings revealed diffuse large B-cell malignant lymphoma. He was treated by combination chemotherapy and remission was achieved. He was discharged in June and remained in remission, but was readmitted for right pleural effusion in October 1994. Effusion was chylous and the chylomicron level was estimated to be 181 mg/dl. Liver cirrhosis also developed but there was no chylous ascites. Chylorrhea disappeared after continuous aspiration, but recurred in December. Continuous aspiration was ineffective, therefore 10 KE of OK-432 was administered twice into the pleural cavity, and chylorrhea again disappeared. No findings suggestive of malignant lymphoma were not detected by computerized tomography and gallium scintigram. He was discharged in March 1995 and chylothorax has not recurred since. These findings suggest that the fragility of the thoracic duct which had been infiltrated by malignant lymphoma might increase, resulting in rupture, even if in remission.

A 77-year-old man, in whom chronic myeloid leukemia (CML) had been diagnosed in October 1990, was admitted to hospital with right chest pain in November 1992. Bone marrow examination revealed the chronic phase of CML. Chest X-ray showed right pleural effusion. The cells from pleural effusion were positive for CD7, CD13, CD33, CD41a, including CD33, CD41a-double positive cells in 57.5%. Southern blot analysis revealed 3'bcr rearrangement. Electron microscopic examination showed the presence of platelet peroxidase. An abnormal karyotype with various additional chromosomes was observed. This is a rare case of extramedullary pleural myelo-megakaryoblastic biphenotypic crisis during the chronic phase of CML.

A 60-year-old man was admitted with general fatigue and jaundice of one year's duration in February, 1981. The hemoglobin (Hb) was 11.4 g/dl and reticulocytes were 1.7%. A diagnosis of chronic cold agglutinin disease (CCAD) was made from the presence of cold agglutinin (CA) 1:2,048, increased serum IgM 267 mg/dl and indirect bilirubin 1.4 mg/dl. His Hb was approximately 11 g/dl in summer and 9 g/dl in winter for the subsequent ten years without therapy. In July, 1990, he was readmitted because of exacerbation of anemia and hepatosplenomegaly. The Hb was 4.6 g/dl, indirect bilirubin 3. 1 mg/dl, CA titer 1:232,144 and reticulocytes were 20%. Serum IgM was 1,065 mg/dl, and immunoelectrophoresis showed IgM-kappa M-protein. Peripheral blood lymphoid cells expressed surface membrane immunoglobulin (SmIg) M and kappa. The bone marrow showed an increased number of lymphoid cells which also expressed SmIg M and kappa. These findings were compatible with those of the features of primary macroglobulinemia (PMG). The M-2 protocol resulted in decrease in serum IgM and CA, but he died of heart failure in February, 1991. The relationship between CCAD and PMG in relation to the pathogenesis was discussed.

Iron deficiency anemia is the most prevalent among form of anemia in the world. In Japan, there is no overall report concerning prevalence and pathogenesis of iron deficiency. We estimated the prevalence of iron deficiency from the results of a survey of 3,015 Japanese women. The reference range for hemoglobin was derived from the average value of subjects with normal iron status (> or = 16% of transferrin saturation and > or = 12 ng/ml of serum ferritin). Using these reference standards, the prevalence of iron deficiency anemia, latent iron deficiency, storage iron deficiency, normal and others were 8.5%, 8.0%, 33.4%, 43.6% and 6.5%, respectively. The prevalence of iron deficiency anemia increased beginning in early lower teen girls, was highest in high teen-girls and, young women and decreased in elderly women. In elderly women, the cause of iron deficiency was often obvious associated with anemia of chronic disorders. The strategy for iron deficiency was discussed concerning iron fortification, mega-ingestion of vitamin C and low dose administration of iron tablets in the higher incidence group.

A 54-year-old man who had been known to have a high prolymphocyte count for four years was admitted to our hospital because of dyspnea in September, 1990. Physical examination revealed skin eruption, lymphadenopathy and hepatosplenomegaly. Chest X-ray demonstrated bilateral pleural effusions. The leukocyte count was 232,900/microliter with 99% lymphoid cells possessing single nucleoli. The cells expressed the phenotype CD2+, CD3-, CD4+, CD7+, and CD8-. Southern blot analysis of DNA from these cells revealed monoclonal rearrangement of T-cell receptor beta-chain genes. Anti-human T-cell lymphotropic virus type 1 (HTLV-1) antibody and HTLV-1 proviral DNA were not detected. A biopsy specimen from the skin lesions showed infiltration of the leukemic cells which were positive for anti-MT1 antibody. Histological finding of the axillary lymph node was malignant lymphoma, diffuse, medium-sized, T-cell type. Combination chemotherapy resulted in the improvement of skin eruption, lymphadenopathy, hepatosplenomegaly and pleural effusions, although his prolymphocyte count increased to 910,000/microliters. He died of cerebral bleeding in July, 1991. We diagnosed this case as T-cell prolymphocytic leukemia, observed for five years.

A 62-year-old woman was admitted to our hospital because of general malaise in May, 1987. No hepatosplenomegary, skin eruption or lymphadenopathy was detected. Laboratory examinations showed mild anemia, thrombocytopenia, normal leukocyte count with no lymphocyte abnormality, hypogranular neutrophils, elevated serum lactic dehydrogenase, increased C-reactive protein and hypoxia. Bone marrow aspirate was normocellular with dysplastic changes in erythroid and megakaryocytic lines which agree with a diagnosis of myelodysplastic syndrome (MDS). She was treated with prednisolone which relieved her symptom but she developed high fever, hemiplegia and disturbance of consciousness and died in August, 1987. Necropsy of the kidney revealed large mononuclear cells within the lumen of small blood vessels. Immunohistochemical study of these malignant cells showed positive reaction to the anti-LCA and anti-L26 antibodies. And electron microscopy showed no azure granules in these cells. Then we diagnosed as neoplastic angioendotheliosis (NAE). To our knowledge, this is the first report of NAE with abnormalities in myeloid, erythroid and megakaryocytic lineages. These results suggest that NAE with MDS originate from a multipotent stem cell.

A 75-year-old man was admitted to our hospital because of hepatosplenomegaly, generalized lymphadenopathy and lymphocytosis in February, 1989. The leukocyte counts were 93,200/microliters with 95% small lymphocytes which expressed surface membrane immunoglobulin (SmIg) M, D and kappa. Histological finding of the cervical lymph node was diffuse small cell lymphoma. A diagnosis of chronic lymphocytic leukemia (CLL) was made. He was followed up without chemotherapy. In January, 1990, he was re-admitted because of progressively enlarged lymph nodes and increased white blood cell counts, up to 183,200/microliters with 98% lymphocytes. He was treated with vincristine, cyclophosphamide, prednisolone. The leukocyte counts decreased to 5,000/microliters and lymph node swelling decreased in size. In April, 1990, generalized lymphadenopathy re-appeared. The biopsied lymph node specimen showed diffuse large cell non-Hodgkin lymphoma (NHL-DL). The lymph node cells were found to express SmIgM and kappa. The diagnosis of Richter's syndrome was made. DNA analysis using Southern blot method revealed identical immunoglobulin heavy and kappa chain gene rearrangements in the two neoplasms. These findings suggest that the CLL cells and the NHL-DL cells originate from the same clone in this case.