A 27-year-old man was admitted to our hospital with the complaint of general fatigue. He had cervical and mediastinal lymphadenopathy. Laboratory examination revealed anemia, hypergammaglobulinemia, and increased levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). A chest radiograph showed opacities in both lung fields. Pathological findings from thoracoscopic mediastinal lymph node and lung biopsies were compatible with multicentric Castleman's disease (MCD), plasma cell type with pulmonary involvement. Chemotherapy combined with radiation therapy resulted in no improvement of his lymphadenopathy and inflammatory symptoms. Eight mg/kg humanized anti-human IL-6 receptor antibody (tocilitumab) was thus administered biweekly. Soon after initiating the tocilitumab treatment, the patient's general fatigue disappeared, and anemia, CRP, ESR, hypergammaglobulinemia and lymphadenopathy all improved remarkably. Further treatment with tocilitumab for two years resulted in maintenance of this good response without any severe adverse events, but the pulmonary findings showed no obvious improvement. Tocilitumab therapy was effective in this MCD patient, however its influence on concurrent lung disease needs to be investigated further.

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We report the successful treatment of a disseminated Fusarium infection with skin manifestations in a severely neutropenic patient. A 51-year-old man with acute myeloblastic leukemia (M4) underwent two courses of remission induction therapy with cytarabine and daunorubicin. Despite prophylactic treatment with tosufloxacin and micafungin, the patient developed a febrile scrotal ulcer. Eight days later, we noted the appearance of painful and diffuse cutaneous nodules and a plain chest X-ray disclosed multiple nodular lesions. Microbiological examination of the scrotal ulcer revealed infection by Fusarium solani, which was also confirmed by both histological and microbiological examination of the skin nodules. Although the patient was treated with amphotericin B (AMPH-B), the clinical symptoms worsened. After AMPH-B was replaced with voriconazole (VRCZ), the patient's symptoms and chest radiographic findings dramatically improved. Thus, VRCZ might be an alternative therapy for patients with neutropenia who have fusariosis that is refractory or unresponsive to AMPH-B.

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We experienced two cases of heparin-induced thrombocytopenia (HIT) which occurred during unfractionated heparin treatment. The first patient was a 72-year-old man, who was admitted to our hospital because of sudden onset dyspnea in January 2000. He was diagnosed as having a pulmonary embolism and heparin was started. Nine days later, progressive embolization of the pulmonary artery and femoral vein was found and thrombocytopenia (platelet count 20×10⁹/l) was observed 14 days after that. Cessation of heparin and administration of argatroban resulted in progressive normalization of the platelet count. The second patient was a 62-year-old woman, who was admitted to our hospital in April 2001, with the chief complaint of sudden onset dyspnea. She was diagnosed as having acute left-sided heart failure and heparin was started. Fifteen 15 days later, thrombocytopenia (platelet count 17×10⁹/l) was observed. Cessation of heparin resulted in normalization of the platelet count. Both cases were positive for anti-heparin-platelet factor 4 (PF4) antibody. Here we report on the clinical course of two cases of HIT with a review of the literature.

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Aleukemic leukemia cutis is a rare form of leukemia manifestation, defined as a skin infiltration of leukemic cells with no evidence of leukemia in the bone marrow. A 4-month-old girl was referred to our hospital because of exanthema that appeared and regressed repeatedly. Histological examination revealed partial infiltration of histiocytic cells in the skin lesion. However, the diagnosis could not be made at that time. At 9 and at 13 months old, appearances of exanthema similar to the previous time were combined with systemic fever, abnormal coagulation tests, and the marked increases of atypical lymphocytes in peripheral blood: however, these symptoms resolved spontaneously. At 14 months old, deterioration of the exanthema and an increase in the peripheral leukocyte counts were observed. Bone marrow aspiration revealed the predominance of monocytic blasts (76.4%), and the patient was diagnosed as having acute monocytic leukemia (M5b) with leukemia cutis. Complete remission was obtained with standard chemotherapy. Six months after the therapy was completed, an extramedullary relapse occurred in the inguinal lymph nodes, which was successfully treated with allogeneic bone marrow transplantation from an HLA-matched unrelated donor, and the patient has been free of disease for two years after the transplantation.

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Tetrasomy 8 is a rare chromosomal abnormality in acute leukemia, and it has recently been considered as a poor prognostic factor. A 20-year-old woman was admitted because of purpura on the upper and lower limbs in February 2002. On admission, her leukocyte count was 6.5×10⁹/l with 66% of blasts, the hemoglobin level was 11.2 g/dl, and the platelet count was 101×10⁹/l. The bone marrow aspirate contained 85.6% of peroxidase-negative, α-naphthyl-butyrate esterase-positive, and CD4+CD56+blast cells. Karyotypic analysis of the bone marrow cells showed 48, XY, +8, +8[17]/47, XY, +8[3]. The patient was diagnosed as having AML (M5a), and treatment with daunorubicin (70 mg×5 days) and cytosine arabinoside (150 mg×7 days) resulted in a complete remission. She relapsed four months later, however, with an extramedullary tumor in T12. Remission could not be achieved, and the patient underwent allogeneic peripheral blood stem cell transplantation from her HLA-identical mother. Her clinical course was almost uneventful except for a phlegmon in the right leg, but on day 49 a relapse occurred, and she died of acute renal failure on day 73. This case strongly illustrates the characteristic of tetrasomy 8 as a poor prognostic factor in acute leukemia.

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A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) λ-type multiple myeloma was treated with bortezomib. She had been treated with tandem autologous stem cell transplantations and achieved complete remission before her disease relapsed. Sixteen hours after the first administration of bortezomib, an episode of fever, slight consciousness disturbance and vomiting occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l). Serum levels of creatinine, uric acid, and AST were also transiently elevated. Serum interleukin-6 level was also increased after the administration of bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%-reduced dose was administered again along with dexamethasone 26 days later, which caused a moderate increase in LDH levels, but no other symptoms. Further treatment caused no increase in LDH. The treatment was very effective and eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions of bortezomib administration. These findings suggest that a bortezomib-induced rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is needed when treating myeloma patients with this very effective agent.

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We report 4 cases of pseudothrombocytopenia due to platelet cold agglutinins. Case 1 was a 57 y.o. female whose platelet count was 97×10³/μl. Case 2 was a 37 y.o. male with a platelet count of 96×10³/μl. Case 3 was a 74 y.o. male with a platelet count of 28×10³/μl. Case 4 was a 62 y.o. female whose platelet count was 34×10³/μl. The platelet counts in these 4 cases were decreased and blood smears showed platelet clumping in blood drawn in a tube without anticoagulant just after withdrawal, as well as in blood drawn in a tube with anticoagulant. The platelets from these patients agglutinated at a temperature below 10°C (case 1 and 4) and 24°C (case 2). The immunoglobulin class of the platelet cold agglutinins in cases 1, 2 and 4 was IgM. Agglutinated platelets showed no activation marker, such as CD62P, CD63 or CD40L, on the surface of the platelets. The target antigen of cold agglutinins was GPIIb-IIIa in cases 1 and 2. We considered that the detection of platelet agglutination in blood without anticoagulant is important to diagnose pseudothrombocytopenia due to platelet cold agglutinins. Although this disease is considered to be very rare, we suspect that this disease may be misdiagnosed as pseudothrombocytopenia due to the presence of an anticoagulant, and overlooked.

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A 64-year-old male was diagnosed as having autoimmune hemolytic anemia (AIHA) in December 2001. The diagnosis of AIHA was established based on the presence of anemia, hyperbilirubinemia, reticulocytosis, positive Coombs test and serum LDH elevation. Although he received steroid pulse therapy, disturbance of consciousness appeared and the anemia and icterus did not improve. Plasma exchange was carried out to eliminate antibodies as an emergency measure. The patient's symptoms were ameliorated following four courses of plasma exchange. This case represents a case of aggressive AIHA with disturbance of consciousness and refractory to conventional corticosteroid therapy. Plasma exchange rapidly led to complete remission.

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