We tried to treat 13 patients with myelodysplastic syndromes (MDS), leukemias and myeloproliferative disorders, with alfacalcidol for their hematological improvement. Eight of them had MDS, 2 acute leukemia (M3, M4), 1 chronic myelogenous leukemia and 2 primary myelofibrosis. All patients were untreated except for 3 patients (PASA, RAEB, AML-M4) who had been treated with mepitiostane, prednisolone and BH·AC-AMP regimen, respectively, prior to alfacalcidol therapy.
All patients received alfacalcidol orally for at least one month. The dosage of alfacalcidol ranged from 0.25 to 10 μg/day, and the medicine was administrated intermittently when the dosage exceeded 6 μg/day to prevent hypercalcemia.
The therapeutic effectiveness of alfacalcidol was evaluated according to a criteria by Koeffler (Cancer Treat Rep 69: 1399, 1985) with minor modifications. Three patients (PASA, RAEB, CMML) showed partial response, 3 (RAEB, RAEB in T, AML-M4) minor response and rest of the patients did not respond. The hematological improvement of 6 responders was transient (from 1 to 2 months), howewer, one patient (PASA) is still responding to alfacalcidol therapy (0.25 μg/day) for over 12 months.
The dysplastic features of hemopoietic cells in the bone marrow showed no noticeable change during the hematological improvement in these responders, suggesting the improvement was obtained as a result of alteration in the proliferation or differentiation of neoplastic clone.
None of 13 patients developed hypercalcemia. One patient (AML-M4) became excitable on high dose alfacalcidol (10 μg/day).
In conclusion, alfacalcidol therapy is effective in some patients with MDS or leukemias and appears worthy especially in the clinical state in which chemotherapy is not indicated.

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Pretreatment peripheral and/or bone marrow blasts from 14 patients with acute unclassifiable leukemia (AUL) expressing myeloid related cell-surface antigen (CD11) or megakaryocyte-platelet related cell-surface antigen (OKM6), were isolated for further analysis in this study. Among 11 cases of CD11⁺AUL, despite a lack of myeloperoxidase (MPO) activity, one patient's blasts possessed Auer rod in a basophilic cytoplasm and another one's blasts expressed MPO maintaining the same surface phenotype after 20 months of his clinical course. The blast from 2 cases possessed both myelomonocytic and monocyte-specific antigens on the cell-surface, whereas the remaining nine cases completely lacked monocyte-specific antigen which is detectable by monoclonal antibodies, Mo2, My4 and Leu M3 (CD14). In addition, we revealed the presence of MPO protein in the cytoplasm of 3 cases of AUL patients by cytoplasmic immunofluorescence test utilizing monoclonal antibody (MA1). Following these results, the former was diagnosed as acute myelomonocytic leukemia (AMMoL) and the latter as acute myelogenous leukemia (AML) by immunophenotypic analysis using flow cytometry (FACS IV) and cytoplasmic immunofluorescence test.
We have also described three cases of acute megakaryocytic leukemia which were demonstrated by the presence of megakaryocyte-platelet-related cell-surface antigens detected by utilizing flow cytometry and monoclonal antibodies in addition to both the PPO activity which was shown by ultrastructural cytochemistry, and the emergence of differentiation antigens while culturing these leukemic cells. The blast of 1 case possessed both platelet GPIb and GPIIb/IIIa cell-surface antigens detected by 5F1 (CD36), AN51 (CDw42), and J15, P2 and HPL2 (CDw4l), respectively, whereas the remaining two cases almont lacked the GPIb cell-surface antigen. Hence, the former was diagnosed as immature (pro) megakaryocytic leukemia and the latter as acute megakaryoblastic leukemia from the viewpoint of immunophenotypic analysis as will be discussed in this article.
These leukemic blasts did not express both T-cell lineage antigens which are detectable by monoclonal antibodies, T6 (CD1), T11 (CD2), T3 (CD3), T4 (CD4), T1 (CD5), Tp40, Leu9 (CD7), T8 (CD8), and B-cell lineage antigens which are detectable by monoclonal antibodies, B4 (CD19), B1 (CD20), B2 (CD21) and J5 (CD10).
The utilization of monoclonal antibodies for identification or characterization of heterogeneous AULs should therefore permit us, not only to define these tumors of myeloid and megakaryocytic cell origin, but also to accurately identify the state of differentiation and their relationship to their normal counterparts, the myeloid and megakaryocytic cell. In addition, accurate diagnosis of AULs with monoclonal antibodies will certainly contribute towards the acquirement of effective therapies for the cure of AULs by the means of various kinds of clinical applications.

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The content of platelet adenine nucleotide in chronic myeloproliferative disorders (CMPD) and multiple myeloma (MM) was measured by a luciferin-luciferase method by Holmsen and Weiss. The release of ATP and ADP from platelet during aggregation induced by collagen and epinephrine were analyzed. The total 42 investigated cases consisted of 11 cases of polycythemia vera (PV), 7 cases of essential thrombocythemia (ET), 7 cases of chronic myeloid leukemia (CML), 9 cases of blastic crisis of CML (BC-CML), and 8 cases of multiple myeloma (MM). The healthy control was 19 cases. In CMPD and MM, the amount of ATP was normal in spite of decrease of ADP; therefore, the ratio of ATP/ADP increased. On the other hand, the ATP significantly increased in BC-CML. MM revealed a remarkable increase of ATP release due to the aggregation by collagen and epinephrine. The maximal rate of aggregation of collagen and epinephrine using Lumi-aggregometer indicated a positive relationship with the ATP release by the Holmsen and Weiss' method. The platelet volume in CMPD increased showing correlation with ATP content and not with ADP. In conclusion, CMPD and MM are regarded as acquired qualitative disorders of platelets or secondary storage pool diseases from the view points of the abnormalities in ATP, ADP contents and their release. However, BC-CML and MM revealed some different change from that of CMPD.

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Eight children with Philadelphia (Ph¹) chromosome positive chronic myelocytic leukemia (CML) were available for cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis as compared to the features of adults with Ph¹-positive CML. In chronic phase additional abnormalities other than Ph¹ chromosome were found in none of our cases. On the other hand, in blastic crisis all of 6 cases had additional chromosomal abnormalities like as i(17q), double Ph¹ and +8. The frequency of the appearance of additional chromosomal abnormalities, especially i(17q), is higher in children than in adult cases. In the DNA of 7 of 7 examined patients, rearrangement of bcr could be demonstrated by Southern blot analysis. These findings were similar to those observed in adults. An analysis of the location of the bcr breakpoint indicated that 5' breakpoints were found in four cases who were long-term survivors, and two of the other cases had blastic crisis from the onset of the disease.
These findings showed the cytogenetic findings of children with Ph¹+CML were different from those of the adult cases in the frequency of the appearance of the additional chromosomal abnormalities, and the location of the bcr breakpoint in children cases might be different from that in the adult cases and influence its prognosis.

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The laboratory findings of 20 patients with untreated megaloblastic anemia due to vitamin B₁₂ deficiency were analysed. The material consists of 13 patients with pernicious anemia, 6 with postgastrectomy B₁₂ deficiency and one with malabsorption syndrome. Hematological data (RBC, Hgb, Ht, WBC, Plt) were correlated with each other and serum LDH levels. Megaloblastic changes of bone marrow were apparent in cases of which Hgb values were below 9g/dl, although its change were not clear in cases with mild anemia (above 9g/dl). However, giant metamyelocytic changes of bone marrow were seen even in cases with mild anemia. Serum B₁₂ levels in 6 out of 19 cases (31.6%) measured by clinical laboratory center were within normal range. In contrat, its level in all cases measured by radiodilution assay using R-protein or intrinsic factor were lower than normal values. Serum B₁₂ levels measured by the latter method were correlated with various hematological data and also related with hematological severity, although its level measured by clinical laboratory did not have any correlation with hematological data. Schilling test seemed to be unreliable, because sample volume which was suggested by kit manual was too small (2ml) to catch enough radioactivity for accurate measurement. Serum methlmalonic acid levels measured by gas capillary mass spectrophotometry were higher than normal valuas in all cases and were well correlated with hematological data.

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The clinical picture and disease features of chronic neutrophilic leukemia (CNL), a rare hematological disorder, were investigated among 38 patients collected from Japanese reports.
According to the diagnostic criteria, review of Japanese literature was carried out, using the questionnaire to the reportors of CNL cases. The rate of return for the questionnaire was 23/29 (79.3%). Of the 38 CNL patients, 26 were men and 12 were women. Their mean age at diagnosis was 65.2 years. The mean value of initial laboratory data were as follows; leukocyte count 54,000/mm³ with 86.9% mature neutrophils, hemoglobin 10.6 g/dl, platelet count 22.0×10⁴/mm³, NCC from the bone marrow 44.9×10⁴/mm³, and NAP score 400.5. The CFU-C value was decreased in 17 of 24 cases examined. Two among the thirteen cases showed an increase of CSF activity in serum, and none was detected in urine of four cases.
The clinical course in 33 cases were evaluated, and the median survival after the diagnosis was 21 months. Three cases terminated blastic crisis. Two had features similar to polycythemia during their course. The association with monoclonal gammopathy or multiple myeloma was found in 8 cases (21.8%), and this appears to be among the presenting clinical characteristics. Hemorrhagic diathesis was often fatal and was the most frequent cause of death (13 out of 28 cases died). Postmortem examination showed occasional systemic infiltration with neutrophils or leukemic cells in most organs including liver and spleen.

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A 40-year-old man who was resected ascending colon and terminal ileum (10 cm) in Aug. 1978, with the diagnosis of Crohn's disease, was admitted to our hospital with general fatigue, paresthesia and tremor in May. 1984. A peripheral blood examination on admission revealed Hb 10.1 g/dl, RBC 234×10⁴/mm³, MCV 131.4 fl, MCH 43.2 pg. A bone marrow specimen showed marked erythroid hyperplasia (W/E 1.44) with megaloblastic change. While serum folate level was normal, serum vitamin B₁₂ value was low and Schilling test showed vitamin B₁₂ disabsorption. Roentgenologic and endoscopic examinations revealed diffuse cobble stone appearances in small intestine (from anastomosis part to duodenal bulb). These examinations suggested vitamin B₁₂ disabsorption with diffuse Crohn's disease caused megaloblastic anemia.
The patient had been treated with vitamin B₁₂ 1,000 μg/day injection and, in Sep. 1984, he recovered from megaloblastic anemia (Hb 13.4 g/dl, RBC 440×10⁴/mm³, MCV 90.7 fl, MCH 30.4 pg).

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A 53-year-old female, who had been having xerostomia and xerophthalmia for two years, was admitted in November 1984, because of subfever and malaise. Laboratory examination revealed pancytopenia with appearance of blasts, mild hypergammaglobulinemia, and elevated titers of ANA, anti SS-A and anti SS-B. Bone marrow aspirate showed increased myeloblasts. Schirmer's test and Rose Bengal's test were both positive, and cyarograph showed apple tree like appearance. Pathological findings of biopsied lip mucosa showed remarkable infiltration of lymphocytes. The patient was diagnosed acute myelocytic leukemia and Sjögren's syndrome.
In spite of recovery of peripheral blood after combination chemotherapy (BHAC-DMP), a disturbance of conciousness appeared and she died of its progression.
It was suspected clinically that she was suffered from progressive multifocal leukoencephalopathy (PML).
It is sometimes reported that patients with Sjögren's syndrome develop malignant lymphoma, but it is very rare that Sjögren syndrome develop AML.

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A 56-year-old female was admitted for the examination of leukocytosis in May, 1982. The hematological examination showed hemoglobin 12.0g/dl, platelets 14.5×10⁴/μl and leukocytes 18,000/μl with 28% of monocytes. A bone marrow aspiration revealed granulocytic hyperplasia. Granulocytes showed nuclear abnormalities, such as folding or lobulation. From these data, a diagnosis of chronic myelomonocytic leukemia (CMMoL) was made and followed with no treatment for 2 years.
However, fever, bone pain, anemia, thrombocytopenia and the increase of monoblasts in the peripheral blood and bone marrow were observed in May, 1984. These findings indicated that she was in the blastic phase. She was treated by intensive combination chemotherapy (BHAC-AMP), but did not attain any remission. Therefore, a small dose of N⁴-behenoyl-1-β-D-arabinofuranosylcytosine (BH-AC; 1 mg/kg/day) was administered for 70 days. As a result, complete remission was obtained and continued for 37 months with the same therapy.
The experience of this case suggests that small dose of BH-AC could be applied to a case of CMMoL in blastic crisis.

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A 34-year old female was admitted to our clinic because of fever and general fatigue on March 26, 1987. On admission, peripheral blood (PB) revealed pancytopenia. Bone marrow smears revealed 9.0% of promyelocytic cells with or without Auer rods. Diagnosis of RAEB in transformation was made. Chromosome study of the bone marrow cells showed t(15;17) in 3 out of 20 cells analysed. After 3 months, the leukemic cells were observed in PB and increased in number. Then the patient showed bleeding tendency and fibrin degradation products (FDP) increased up to 40 μg/ml. And the leukemic cells were over 30% in PB at the end of July, 1987. The diagnosis of APL with DIC was made.
To our knowledge, this is the first case of APL with a history of MDS with t(15;17).

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Sixteen-years-old female with severe aplastic anemia received a therapy combined with antilymphocyte globulin (ALG), high-dose methylprednisolone (m-PSL) and danazol. At the hospitalization, hematological examination demonstrated as follows; reticulocyte 21,000/μl, granulocyte 350/μl, platelet 10,000/μl and hypocellular bone marrow. Treatment schedule were 1) m-PSL 1,000 mg (day 1-4), 500 mg (5-8)—then tapered. 2) ALG lg/day (day 4-8) 3) danazol 600 mg/day. During ALG administration, leukocytopenia and thorombocytopenia appeared but thereafter hematological recovery was obtatined and the patient was free from supportive care. She developed mild diabetes meritus and moderate liver dysfunction, neverthless, both of which were controlled. At 3 months after the begining of the treatment, hematological examination demonstrated as follows; reticulocyte 236,000/μl, granulocyte 1,900/μl, platelet 56,000/μl and normocellular bone marrow. Although this immunosuppressive therapy was remarkablly effective to this patient, immunological relation to the onset of aplastic anemia was not demonstrated in in vitro examination. This combined therapy seems to be effective one for patients with severe aplastic anemia.

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A male with myelodysplastic syndrome (MDS) following aplastic anemia is reported. The patient had been diagnosed as aplastic anemia at 8 years of age, and treated with blood transfusions, anabolic and glucocorticoid steroid hormones. Over a period of subsequent twelve years, he had remission and deterioration. At the age of 21, the patient developed a sudden progression of severe anemia, when his bone marrow showed hyperplasia with prominent dyshematopoiesis and excess of blasts, compatible with MDS by the definition of FAB classification. He received low dose Ara-C therapy, which was ineffective. Nine months later he developed acute monocytic leukemia (M5b) and died. Chromosomal analysis revealed 46, XY at the onest of aplastic anemia, 46, XY, del (6) (q21 q27) at the MDS and 46, XY, -7, +21, 6q-/47, XY, +Y, -7, +21, 6q- at the acute leukemic stage.

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This is a case report of a successful case of surgical treatment of a lung abscess formed from pulmonary aspergilloma in a patient with a recurrence of acute promyelocytic leukemia during remission induction therapy.
A 39 year-old woman was admitted to our hospital for remission induction therapy of a recurrence of acute promyelocytic leukemia. We were successful in bringing her to a state of complete remission by a therapy of a intermediate-dose of Ara-C. Pulmonary aspergilloma was formed in the right lung during therapy. We performed transbronchial infusions to Amphotericin B which dissipated the fungus ball.
However, a lung abscess was formed. We needed radical therapy, and there were no complications in the following surgical treatment.
Recently, along with the tendency for the use of stronger chemotherapy treatment regimes for acute leukemia, there has been an increase of the number of mycosis cases such as the pulmonary aspergilloma case reported here. Accordingly, surgical treatment is becoming more and more a matter of necessity in the clinical course of leukemia patients.

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A 88-year-old man was admitted because of the left chest pain due to herpes zoster for 1 week. Blood analyses and immunoelectrophoresis revealed anemia, severe neutropenia, rouleaux formation and IgM, λ-type monoclonal gammopathy. The HE staining and peroxidase-anti-peroxidase staining of biopsy specimens of the cervical lymph node swelling appeared from the fifth hospital day, revealed an increase in atypical lymphocytes bearing IgM, λ-type immunoglobulin. Then a diagnosis of primary macroglobulinemia was made. Although the patient's clinical findings transiently improved after chemotherapy with prednisolone and vindesine, he died of a septic shock which appeared after klebsiella pneumonia and sepsis. We reported an unusual case of primary macroglobulinemia with severe neutropenia, leading to a rapid development of septic shock after the chemotherapy.

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A 12-year-old boy with hepatocellular carcinoma presented with marked neutrophilia up to 69,200/μl and elevation of serum colony stimulating activity (CSA) and burst promoting activity (BPA).
After resection of the tumor, neutrophil count returned to the normal value and hemopoietic activites in serum decreased. However, on relapse, both elevated to the preoperative levels.
Hemopoietic activities in the medium conditioned with tumor tissue were investigated using normal human bone marrow as the target cells, and both CSA and BPA were demonstrated.
From these findings, it could be considered that the tumor tissue produced a substance that stimulated both myelopoiesis and erythropoiesis.

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A 60-years-old woman with polycythemia vera with marked thrombocytosis and untolerable erythromelalgia was presented. A single dose of 400 mg aspirin was effective to improve the pain and cyanosis. And we studied the relationship between platelet aggregation rate and symptoms after administration of several antiplatelet drugs. A single dose of 100, 200, 400 and 800 mg aspirin, 25 mg indomethacin (Id), 200 mg OKY-046, and daily dose of 300 and 600 mg dipyridamole (Dp) and 300 mg ticlopidine (Tc) were given. Aspirin, Id and OKY-046 were effective for the improvement of finger pain. The complete inhibition of spontaneous aggregation (SPA) and aggregation by 2.0 μg/ml of collagen were well parallel with the improvement of symptoms. But duration of effect of OKY-046 were only 6 hours. Dp and Tc were not effective for the improvement of pain, had no relation with platelet aggregation rate. The concentration level of aspirin in vivo which suppresses the platelet aggregation induced by SPA and 2.0 μg/ml of collagen coincided well with the concentration level of this drug which suppresses the same platelet aggregation in vitro. It seems to be useful to suppress the platelet aggregation induced by SPA and 2.0 μg/ml of collagen with aspirin and Id for controlling the platelet aggregation induced circulatory disturbance in patient with thrombocytosis.

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A 42-year-old woman was admitted to our hospital because of easy fatigability in Jan. 1976. Laboratory examination revealed severe macrocytic anemia and slight lymphocytosis. She was diagnosed as having pure red cell aplasia (PRCA). She went into hematological remission 6 weeks following 40 mg/day treatment with prednisolone, but the anemia relapsed frequently when the dosage was lessened. She was then treated with 50 mg/day of cyclophosphamide, 50 mg/day of azathioprine, splenectomy, and methylprednisolone pulse therapy, but the recovery from anemia was temporary after each treatment. Since 1984, peripheral lymphocyte counts were 1∼30,000/μl, and reticulocyte counts were 0. She died of sepsis of Listeria in Sep. 1986.
Peripheral lymphocytes had large azurophilic granules and an immunophenotype of OKT3+8+11+Ia1+Leu7+.

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A 67-year-old man was admitted in October 1987 with complaints of nausea, headache, dizziness and speech disturbance. Hematological examination showed pancytopenia. Bone marrow aspiration failed with a dry tap. A month later, the second aspiration showed hypocellular marrow containing 18.2% of lymphoma cells. Physical examination showed splenomegaly and lymph node swelling. Polyclonal hypergammaglobulinemia was not observed. A lymph node biopsy exhibited typical histology of immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. Surface marker CD3 and CD4 positive cells were dominant. The patient complained of epigastric pain and occult blood was positive in stool. Gastrofiberscopic examination disclosed well differentiated adenocarcinoma in situ located on a polyp, and polypectomy was performed. Lymphoma was treated whth cyclophosphamide, doxorubicin, vinblastine and prednisolone. Splenomegaly and lymph node swelling were reduced in size but the effect was temporary. Thereafter the patient has been treated with cyclophosphamide, doxorubicin, vindesine, prednisolone and etoposide every 3 weeks. This is our first case report of IBL-like T cell lymphoma associated with early gastric cancer.

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A case of immunoblastic lymphadenopathy like T cell lymphoma (IBL like T cell lymphoma) associated with biclonal gammopathy is reported. The patient is a 79 year-old male who was admitted to our hospital for generalized lymphadenopathy in January 1987. The lymph node biopsy revealed complete architectual effacement with replacement by a diffuse cellular infiltrate of immunoblasts and pale cells which have a T cell phenotype. A diagnosis of IBL like T cell lymphoma was made. Of interest, high serum level of IgG (6,630 mg/dl) was noted, and immunoelectrophoresis revealed biclonal gammopathy (IgGκ, IgGλ), but no remarkable abnormalities were found in the bone marrow aspiration and bone survey. We treated the patient with two courses of CHOP thrapy, which resulted in marked improvement of generalized lymphadenopathy and disappearance of biclonal gammopathy. However, relapse was noted a month later without reappearance of biclonal gammopathy. The rebiopsy of lymph node revealed a new appearance of Lennert's lesions and decrease of immunoblasts in number. The patient received two courses of M-BACOD therapy, which achieved complete remission, and the patient remained in remission for more than 17 months.

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Rapid and complete hematopoietic reconstitution was achieved in a child with T cell acute lymphoblastic leukemia who was autografted with peripheral blood stem cells (PBSC). A large number of PBSC was collected by two courses of 3∼4 hour-lasting lymphopheresis during early remission induced by the second-line chemotherapy and then cryopreserved in liquid nitrogen. A myeloid progenitor cell dose of 203×10⁴ CFU-GM/kg body weight was reinfused to the patient followiog marrow-ablative chemotherapy (MCNU 600 mg/m², cytosine arabinoside 6 g/m², etoposide 300 mg/m², cyclophosphamide 160 mg/kg). Neutrophil count reached 0.5×10⁹/l by day+7 and platelet count reached 20×10⁹/l by day+9. Thereafter, white blood cell count continued to increase and reached a maximum of 38×10⁹/l on day+14. Thus, the rapid recovery of hematopoiesis minimised marrow aplasia-related risks. This approach of stem cell rescue operation can be applied to the treatment of children with cancer, who otherwise have no hope to be cured, as an alternative to bone marrow transplantation.

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