Eighteen patients underwent allogeneic bone marrow transplantation (allo. BMT) during the period May, 1991 to December, 1992 in the Center for Adult Diseases, Osaka. They were monitored for cytomegalovirus (CMV) antigenemia and arterial oxygen saturation (SaO₂). More than 10 antigenpositive cells per 50,000 polymorphonuclear leukocytes were detected in five of 18 patients. Three of these 5 patients developed CMV pneumonia several weeks after the first detection of more than 10 positive cells. Six of 18 patients developed interstitial pneumonia (IP) (3 CMV pneumonia and 3 idiopathic IP). SaO₂ decreased less than 95% several days before the development of IP in 3 of these 6 patients (2 of CMV pneumonia and 1 of idiopathic IP). CMV antigenemia assay and SaO₂ assay were thus both considered to be useful for the early detection or prediction of development of CMV pneumonia.

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Combination chemotherapy regimens using multiple agents have been reported to produce long term survival in patients with non-Hodgkin's lymphoma (NHL). However, the adverse effects of those regimens, particularly pulmonary complications, have resulted in fatalities. We measured P-III-P and type IV collagen-7S level in the serum and BALF of 23 previously untreated NHL patients who underwent COP-BLAM III chemotherapy in which a high dose of bleomycin (BLM) was used, and studied the relationship between those parameters and the pulmonary functions in those patients. The parameters and pulmonary function were measured before the first course and after the completion of the fourth course of chemotherapy. As for pulmonary function, chemotherapy produced an increment of %DLCO value but no change in PaO₂, %VC, and %FEV_1,0. While serum P-III-P levels remained unchanged, P-III-P levels in BALF slightly decreased after the chemotherapy. Type IV collagen-7S levels both in serum and BALF showed no change after the chemotherapy. Serum P-III-P levels after the chemotherapy were significantly correlated with both total cell counts and lymphocyte counts in the BALF. But there was no correlation between serum P-III-P levels and %DLCO. Mild and early-Stage fibrosis was observed in the lungs of the patients who were treated with COP-BLAM III. Pulmonary adverse effects are not likely to be associated with the total administered dose of BLM, but are associated with individual susceptibility to BLM toxicity. Our results suggest that the chemotherapy should be discontinued or the dose of BLM should be reduced if the P-III-P level in BALF increases.

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Anemia and neutropenia caused by copper deficiency is a well-known consequence of long term total parenteral nutrition in the literature. We present 6 bed-ridden elderly patients who developed anemia and neutropenia after receiving enteral nutrition for a long time (mean: 3.3 years) In all 6 patients, serum copper and ceruloplasmin level were very low, and the mean of their hematological data were as follows: WBC 2,200/μl, neutrophil 554/μl, hemoglobin 8.1 g/dl, platelet 260×10³/μl, respectively. The bone marrow examination showed cytoplasmic vaculization of both myeloid and erythroid precursors, and maturation arrest of granulopoiesis. Then, copper sulfate was administrated by enteral tube to 6 patients, and the improvement of anemia and neutropenia was observed within a month. A 82-year-old woman who received enteral nutrition for 3.5 years with sever anemia (Hb 3.7 g/dl) and neutropenia (neutrophil 350/μl), showed a marked improvement in hematological data (Hb 8.0 g/dl, neutrophil 4,092/μl, respectively) after two months by administering the copper supplementation. The exact cause of the anemia and neutropenia in copper deficiency is unclear, but it is suggested that the decreased activity of enzyme containing copper may be related. Hematological abnormalities due to copper deficiency should be cared during long term enteral nutrition with long termed bed-ridden elderly patients.

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To evaluate the efficacy and safety of subcutaneous administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in aplastic anemia (AA), 21 patients were given a daily subcutaneous dose of 200μg/m² of KRN8601 for 4 weeks. When the blood neutrophil count did not reach 2,000/μl within 2 weeks, the dose was increased to 400μg/m². A marked neutrophilic response was obtained in all 9 patients with non-severe AA and in 9 out of the 12 patients with severe AA, yielding a response rate of 85.7%. Adverse effects included lumbago in one patient and elevation of serum enzyme levels in 6 patients, but did not prohibit further treatment. These results suggest that subcutaneous administration of KRN8601 is safe and useful in improving neutropenia in AA.

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To evaluate the safety and efficacy of subcutaneous administration of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes (MDS), 20 patients were given a daily dose of 50μg/m² of KRN8601 for 4 weeks. When the blood neutrophil conut did not reach 2,000/μl within 2 weeks, the dose was increased to 100μg/m². A marked neutrophilic response was obtained in 17 of the 18 evaluable patients (94.4%), irrespective of the MDS disease type. Five patients showed a platelet increase, 3 of which also showed an erythroid improvement. To maintain neutrophil levels greater than 1,000/μl, 12 patients were treated with KRN8601 for 4 weeks. A dose of 25 to 50μg/m² 3∼4 times a week served to this end in 8 patients and 100μg/m² three times a week or daily in the remaining 4 patients. One patient with RAEB progressed to acute myeloid leukemia 8 weeks after KRN8601. The treatment was well-tolerated in the majority of patients with no severe toxicities. These results suggest that subcutaneous administration of KRN8601 is safe and useful in the treatment of cytopenias in MDS.

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We examined leukemic blasts from 5 cases of AML-M0 diagnosed according to The French-American-British (FAB) classification for expression of immunological markers as well as myeloperoxidase (MPO) using flow cytometry (FCM) and immunocytochemistry (ICC). In one patient, the myeloid antigens, CD13 and CD33, were negative on FCM, but apparently positive in the cytoplasm by ICC, leading to a diagnosis of AML-M0. We examined MPO with anti-MPO monoclonal antibody in four patients by ICC, and could detect 3% or more MPO positive rates in all cases. These findings indicate that immunological studies for MPO and myeloid markers using ICC are very useful for the diagnosis of AML-M0. Two of 5 patients achieved CR, but they relapsed soon or after one year, respectively. The treatment outcomes suggest that the AML-M0 is an AML subtype with poor prognosis.

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A 66-year-old man was treated for IgD (λ) multiple myeloma with 2mg/day melpharan and 20mg/day prednisolone. Subsequently, he developed pneumonia for which he received antibiotics, an antifungal agent and granulocyte colony-stimulating factor (G-CSF) twice. Myeloma cells appeared in the peripheral blood 10 days after the second G-CSF course. In addition, skin tumors developed on his extremities and chest 14 days after the second use of G-CSF. The skin tumors consisted of immunohistochemically IgD (λ)-positive myeloma cells. The skin tumors may have been formed from the bone marrow by metastasis, a very rare occurrence in multiple myeloma. Before the development of the tumors we administered G-CSF, which may also have been related to the formation of the skin tumors.

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Multiple myeloma (IgGκ+IgAκ type, clinical stage IA) was diagnosed in a 82-year-old woman in January 1986. Chemotherapy (melpharan, prednisolone, vindesine, cyclophosphamide). caused prolonged myelosuppression. Therefore she was given other treatment. In October 1992, her peripheral blood examination demonstrated 2% blastic cells and 12% eosinophils. Bone marrow aspiration showed dysplastic features of trilineage blood cells with 4.8% myeloblasts. The karyotype of bone marrow cells from this patients was 47, XX, +der(1)t(1;7)(p11;p11), -7, +8. A diagnosis of therapy-related myelodysplastic syndrome (refractory anemia) was established. Eleven months after diagnosis of myelodysplastic syndrome, she is alive without leukemic transformation.

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In February, 1990, a 49-year-old man was admitted with petechia and gingival bleeding. The peripheral blood showed 5,200 leukocytes/μl including 73% abnormal promyelocytes and 24,000/μl platelets. Bone marrow puncture revealed that nucleated cell count was 331,250/μl including 85.4% abnormal promyelocytes with 46XY, i(17q) chromosome. Coagulation tests revealed DIC. He was diagnosed as having acute promyelocytic leukemia, and he was treated with the BHAC-DMP protocol. He achieved complete remission, and received consolidation therapy and maintenance therapy. However he relapsed in May, 1991 with 46XY, 16q-, i(17q) chromosome. He was treated with BHAC-MV protocol and again achieved complete remission. In June, 1992, he re-relapsed and 3.6% blasts and 10% abnormal promyelocytes was found in his bone marrow. He was treated for 14 days with 15 mg Aclarubicin without any change. Then he was treated with 60 mg All-trans retinoic acid (ATRA). After administration of ATRA, his peripheral blood leukocyte count increased temporarily but bone marrow suppression continued. Then he received continuous subcutaneous infusion of 24 μg/day granulocyte colony-stimulating factor (rhG-CSF). After treatment with ATRA and rhG-CSF, he entered a third complete remission.

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A 60-year old man admitted in November, 1991 because of hyperproteinemia. He had shown a gradual increase in serum levels of γ-globulin since 1981, and idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia was diagnosed in 1989 when he was admitted to another hospital because of persistent swelling of bilateral inguinal lymph nodes since 1986. Multiple swelling of lymph nodes was observed in the right supraclavicle fossa, the left axillary and bilateral inguinal region, and diffuse reticulo-nodular shadows were observed on his chest roentogenogram. Other laboratory findings were as follows; erythrocyte sedimentation rate 143 mm/hr, CRP 3+, Hb 9.4 g/dl, TP 13.7 g/dl with 69.4% of β-γ bridge, BUN 21.1 mg/dl, creatinine 1.6 mg/dl, PaO₂ 77.6 mmHg, plasma cell count in bone marrow 6.4% and positive tests for autoantibodies such as rheumatoid factor, anti-DNA antibody, anti-smooth muscle antibody, and direct Coombs test. Serum interleukin-6 (IL-6) level increased to 259 pg/ml and IL-1β was 39.1 pg/ml. Specimens of both transbronchial lung biopsy and fine-needle kidney biopsy revealed a marked infiltration of lymphocytes and plasma cells into interstitial regions of lung and kidney. We reported here a case of multicentric Castleman's disease (MCD) who also demonstrated lymphoid interstitial pneumonia and interstitial nephritis. The present study suggests that some cytokines including IL-6 and IL-1β may be closely related to the pathophysiology of MCD.

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A 57-year-old man was admitted to hospital because of leukocytosis. He showed mild splenomegaly and, laboratoly studies revealed elevated mature neutrophil count without morpholigical abnormality, mild anemia and elevated neutrophil alkaline phosphatase score. The serum granulocyte colony stimulating factor concentration was below 30 pg/ml. Bone marrow was a dry tap, and biopsy specimen revealed severe fibrosis. The peripheral blood karyotype was 46, XY with no rearrangement of bcr-abl.
The patient was diagnosed as having chronic neutrophilic leukemia (CNL) with bone marrow fibrosis. He was successfully treated with hydroxyurea (HU) 1000 mg/day. The peripheral blood leukocyte was decreased to the normal level and, the bone marrow biopsy specimen changed mild fibrosis. During the follow up period of 11 months, the neutrophil count was well controlled without any side effect. This is a rare case of CNL accompanied with bone marrow fibrosis which was effectively treated by the administration of HU.

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