To detect antigenic sites of platelet-bound autoantibodies in chronic ITP, whole blood or platelet-rich plasma from patients was stained with monoclonal antibodies (MoAbs) directed against platelet membrane glycoproteins (GPs) and with FITC-conjugated anti-mice IgG in an unwashed system followed by flow cytometric analysis. Platelets were identified by light-scattering profile and the amount of anti GP MoAb bound to platelets was measured and expressed as mean fluorescence intensity. This system enabled to quantitate the amount of intact GPs on platelet surface, regardless of activation of platelet.
As a result, decreased amount of platelet-bound anti GPIIb/IIIa MoAb was noted in 5 of 22 patients with chronic ITP comparing to those with normal subjects. On the contrary, none of these patients revealed any demonstrable decrease in the amount of anti GPIb MoAb binding.
From these observations, we suggest that the decreased MoAb binding to platelets in these five patients indicates the binding of autoantibody directed toward antigenic determinants, which are on or close to the epitope of this MoAb.

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We sudied blood coagulation and fibrinolysis in 18 DIC patients with multiple organ failure. Blood was collected three times (1st, 3rd, 6th hospital days) from an indwelling arterial line, and FPA, FPBβ 15∼42, α₂PI-Pl-C, D-dimer, t-PA; Ag, and t-PA activity were measured.
1) Continuous FOY infusion (1.40±0.07 mg/kg/H) resulted in a statistically significant fall of FPA levels, which however, was still above normal. The FPA levels of the patients whose DIC score was not improved or who had massive hematomas were statistically higher than the patients whose DIC score was improved or without hematomas.
2) FPBβ 15∼42, α₂PI-Pl-C, and D-dimer remained at consistently high levels following onset of the DIC. A significant positive correlations were seen between these indices; between the FPA and FPBβ 15∼42, α₂PI-Pl-C.
3) The levels of α₂PI-Pl-C were found to be higher in the patients with hematomas than those without hematomas.
4) T-PA; Ag level remained at consistently high during all hospital day. On the other hand, t-PA activity level did not change significantly. There was dissociation between the t-PA; Ag and the t-PA activity.
5) The patients whose DIC score were not improved on the 6th hospital day had higher levels of t-PA; Ag than the pateints whose DIC score were improved, but there were no differences in the number of the ischemic organs between these patients.
In conclusion, regardless of the continuous FOY infusion some patients revealed the continuous production of thrombin. Consistent high level of plasmin activity is mainly due to the secondary fibrnolysis and partialy due to the primary fibrinolysis and the extravascular secondary fibrinolsis. The DIC patients with the multiple organ failue have increased PAI activity. The presence of increased t-PA; Ag may serve as an effective indicator in the prognosis of the DIC, while FPA data are valuable as a meanes of assessing the effectiveness of anticoagulant treatment.

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We assessed the response of various tumors, following each of three consecutive courses of CHOP or CHOP-Bleo therapy in 32 untreated patients with intermediate or high-grade non-Hodgkin's lymphoma (NHL), and also retrospectively compared these results to those for a group in whom complete remission (CR) had been obtained within five courses and a non-CR group. A low CR rate was observed in these patients who showed no or only temporary antitumor effects (persistent increase, no change, or increase after a transient decrease) after two courses of therapy. Furthermore, we measured total tumor volume and tumor regression rate after each course of therapy in 21 patients who had measurable tumors, and determined thier cut off values for distinguishing between CR and non-CR. When the cut off values were applied to the effects observed in the 21 patients, positive predictive values after each course of therapy were high. False negative values after the second course of the therapy were low, and showed 0% when the cut off value determined from tumor regression rate was used.
These results suggest that we can accurately predict the probability of CR after the second course of CHOP or CHOP-Bleo therapy, although this should be further confirmed by prospective study. In addition, such an analysis may prove useful in setting up individualized response-adapted therapy for NHL.

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To analyse the factors which were related to prognosis at first examination and early diagnosis of relapse in complete remission phase, 26 patients with acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) were investigated.
There was a tight relationship between age and remission rate in patients with M4 and M5. Six of M4 with eosinophilia (M4Eo) patients revealed 83.3% as remission rate with good prognosis in the survival curve. LDH level of them was lower than other patients singnificantly. In order to diagnose relapse before clinical manifestations, it was useful to follow up number of mature monocytes (over 600/μl) in the peripheral blood.

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We examined fibrinolytic substances in homogenate of leukemic cells, normal granulocyte or mononuclear cells fraction. Plasminogen activators (PA) were siginificantly low in normal cells, but they were slightly increased in lymphobastic leukemia cells and markedly increased in myeloblastic leukemia cells. In almost leukemic cells homogenate, the antigen ratio of tissue type PA (t-PA)/urokinase type PA (u-PA) was about 2.0. In especially AMMoL and AMoL, PA activity had discrepancy between euglobulin lysis time and amidolytic assay using chromogenic substrate. AS PA inhibitor (PAI)-II was markedly increased in them, PAI might effect the PA assay. PA activity of leukemic cells homogenate was similar to that without t-PA stimulator and leukemic cells homogenate significantly stimulated t-PA. As both PA activity and antigen were statistically increased in leukemic cells homogenate of patient with disseminated intravascular coagulation (DIC), PA and PA stimulator in leukemic cell might play an important role in hypofibrinogenemia or DIC.

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Between 1973 and 1989, 16 childern with non-Hodgkins lymphoma (NHL) with a mediastinal mass (MM) were treated at our institution with multi-agent chemotherapy and radiotherapy. They also received central nervous system (CNS) prophylaxis including intrathecal methotrexate administration (14 cases) and cranial irradiation (7 cases). Twelve were boys and 4 girls. Median age was 11±3. One patient died of air way obstruction one day after admission. Fourteen of 15 patients entered into complete remission (CR) and one patient partial remission. Five remains in CR 7 to 175 months after diagnosis (median 76 months). Nine patients relapsed in the bone marrow (3 cases), CNS (3), testicles (1), neck lymphnode (1) and bones plus kidneys (1). Of these, 7 patients died within 13 months after initial relapse. The disease free survival (DFS) and overall survival of all patients were 27% and 33%, respectively. Analysis of the prognostic factors among patients with MM⁺-NHL revealed that the serum LDH level below 1,000IU/l was a good prognostic sign. Other factors such as age, stage, initial WBC count, size of MM and response of the MM to the initial treatment did not correlate with DFS. Because of its rarity and the poor treatment result, we need more aggresive treatment program by a multiinstitutional study for MM⁺-NHL.

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To clarify the clinical significance of serum deoxythymidine kinase in various hematological disorders, basic examination was performed of a newly developed radioenzymeassay kit for TK (Prolifigen TK kit “Daiichi”) using ¹²⁵I-iodo-deoxyuridine as a substrate. The assessment of the standard curve, and the results of recovery test, dilution test, and precision and reproducibility were satisfactory. Among several anticoagulant agents tested, heparin was the best one showing no influence on the measurement of TK level. Based on these results, serum TK level was measured in 140 healthy adults as a control group. There was no difference by age and sex. The serum TK level of normal control was 3.1±1.2 U/l, with an upper limit of 5.5 U/l.

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Using Prolifigen TK kit ”Daiichi”, the serum TK level were determined in patients with adult T-cell leukemia (ATL) and its related disorders. The mean level of serum TK at diagnosis was 279.9 U/l in acute type ATL, 27.8 U/l in chronic type ATL, 59.0 U/l in lymphoma type ATL, 3.1 U/l in pre-ATL and 2.4 U/l in HTLV-I carriers. In these patients, six other kinds of tumor markers such as lactic dehydrogenase, β₂-microglobulin, immunosuppressive acidic protein, ferritin, tissue polypeptide antigen and carcinoembryonic antigen were also examined. Among the seven tumor markers, TK level showed the most significant difference among clinical subtypes of ATL. This indicates that the TK level is one of the promising parameters indicative of aggressiveness of ATL cells.

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In a retrospective study to evaluate the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) for the prevention of Pneumocystis carinii pneumonitis, we studied 1760 patients with hematological malignancies over a twenty-year period (1970∼1989).
449 patients received oral SMX-TMP, most of all received 400mg of SMX and 80mg of TMP twice per day.
None of the patients receiving SMX-TMP developed P carinii pneumonitis, whereas twenty-six (2.0%) of the 1311 patients who did not receive SMX-TMP developed P carinii pneumonitis (p<0.01).
We found that the SMX-TMP was very effective in the prevention of P carinii pneumonitis in patients with hematological malignancies, and was well tolerated.

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A case of acute megakaryoblastic leukemia with complex chromosomal abberations is reported. A 63-year-old man was admitted to our hospital because of pancytopenia. Bone marrow aspiration resulted in a dry tap and biopsy showed hypoplastic marrow with fibrosis. Blast cells in the peripheral blood were identified as megakaryoblasts because they were positive for electron microscopic platelet peroxidase (PPO). In addition, monoclonal antibody, TP80, to platelet glycoprotein II b-III a reacted with in about 26% of the blast cells. Chromosomal analysis of the peripheral blood revealed a mosaic pattern of a normal karyotype and abnormal ones, including 44, XY, -5, -7, -18, 10q-, +marker.

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A 57-year-old man was admitted to our hospital with high fever and nasal obstruction. The diagnosis of T cell type malignant lymphoma (T-ML) was made by the biopsy of left nasal cavity tumor. After admission, his general condition was improved by chemotherapy and radiotherapy, but relapsed a month later. He was then treated with chemotherapy, and the partial remission was obtained. During the clinical course, he had a high fever again without any significant infections or exacerbation of T-ML. The data of coagulation system showed DIC. The levels of serum ferritin and LDH were extremely elevated. Bonemarrow aspiration showed markedly increased hemophagocytic histiocytes. These data suggested that he was complicated by DIC and hyperferritinemia closely associated with hemophagocytic histiocytosis a part from the underlying T-ML. Causes of DIC and hyperferritinemia associated with hemophagocytic histiocytosis in the present case were discussed.

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An adult T cell leukemia associated with pure red cell aplasia-like lesion was described in this paper. A 51 year-old woman was admitted because of headache and palpitation in Octber 1988. On admission, physical examination showed marked pallor but no detectable superficial lymphadenopathies. Hepatosplenomegaly was not observed. The blood examination revealed normocytic anemia with Hb of 6.6 g/dl and marked leukocytosis of 18,800/μl with 43% ATL cells. The bone marrow aspirate showed moderate infiltration of ATL cells and a few erythroblasts. The bone marrow biopsy disclosed moderate infiltration of ATL cells, only a few erythroblasts with maturation arrest and marked fibrosis. The erythropoietin in serum was elevated (686 IU/ml). To clarify the mechanism of development of the PRCA-like lesion, the peripheral blood lymphocytes (ATL cells) or serum of the patient was added to in vitro erythroid colony formation. The patient's serum increased BFU-E but either serum or lymphocytes didn't inhibit the growth of CFU-E compared with control.

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A 7-year-old girl was admitted to our hospital because of fever and multiple petechiae following non-A non-B hepatitis. Peripheral blood on admission showed pancytopenia, and she was diagnosed to have hepatitis-associated severe aplastic anemia. She was treated with oxymetholone, prednisolone, 2 courses of bolus methylprednisolone, 2 courses of high dose γ-globulin therapy and ALG (Pressimmun) without success.
Nineteen months after diagnosis, ALG (Lymphoser) and bolus methylprednisolone followed by oxymetholone and prednisolone were tried. Hematologic conditions improved gradually, and have become normal except mild thrombocytopenia over a year. This case suggests that there is a difference in clinical efficacy between ALG preparations, and this observation gives the basis of repeating ALG therapy using a different preparation even if the preceding one has failed.

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A 48-year-old male was admitted to our hospital on April 20, 1989 because of general fatigue and abdominal fullness. Physical examination showed hepatomegaly, massive splenomegaly, and systemic lymphadenopathy. Hematological findings revealed WBC 73,000/μl, RBC 289×10⁴/μl, Hb 8.0g/dl, and platelet 9.1×10⁴/μl. WBC differential count demonstrated a mixture of 63% matured small lymphocytes and 32% prolymphocytoid cells.
Bone marrow aspiration was unsuccessful with a dry tap. Surface marker analysis of peripheral blood lymphoid cells disclosed that they were positive for anti-HLA-DR, CD 5, CD 19, CD 20, CD 21, CD 25, Sm-IgM, Sm-IgD, and Sm-K. He was diagnosed as B-CLL/PL, and treated with VEPA with partial remission. CLL/PL which was advocated by Melo in 1986 is regarded as a distinct clinical entity intermediate between CLL and PLL in clinical and laboratory features. Our case is interesting with regard to good response to combination chemotherapy, though most cases of CLL/PL have a resistance to standard chemotherapy.

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A 35-year-old man was admitted to our hospital because of lumbago on March 25, 1988. On admission white blood count was 1,200/μl with neutrophils of 9% and lymphocytes of 91%, hemoglobin level was 11.2g/dl and platelet count was 55×10³/μl. Bone marrow smear showed 77% leukemic cell including non-specific or specific esterase-positive cells. Chest X-rays showed the presence of mediastinal tumor and diffuse reticular shadows. A diagnosis of ANLL was made and a hematological remission was obtained after one course of combination chemotherapy consisting of BH-AC, daunorubicin and prednisolone, but the enlarged mediastinal tumor and pulmonary infiltration worsened rapidly followed by marked dyspnea. This radiographic abnormal shadow was confirmed to be leukemic infiltration from the finding of transbronchial lung biopsy. We hesitated to give systemic chemotherapy because he also had had liver abscess. Accordingly we performed BAI of ACNU at a dosage of 150mg which led to a dramatic improvement in dyspnea. ⁶⁰Co therapy was performed on the mediastinal tumor. On May 30, when he had a relapse, he was unsuccessfully treated with systemic chemotherapy. The leukemic cells invaded most of the organs and the patient died on July 19, 1988. It is likely that BAI of ACNU for leukemic pulmonary infiltratin was effective.

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Relapsing polychondritis is a rare disorder of uncertain origin characterized by recurrent inflammation of cartilage. A case of myelodysplastic syndrome (MDS) associated with relapsing polychondritis is reported.
A 60-year-old man who had been diagnosed as MDS was admitted because of pain and swelling in the bilateral preauricular regions and cheek. A diagnosis of relapsing polychondritis was made by coexistence of auricular chondritis, arthropathy, occular inflammation and audio-vestibular disturbance. He also developed occular palsies and opticneuritis. He was treated with predonisolone, azathioprine, dapsone, and then with steroid pulse therapy. Moreover, plasmapheresis and high dose γ-globulin therapy were undertaken. However, all these treatments were unsuccessful and he died of respiratory failure.

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A congenital deficiency of protein C (PC) is reported in a 42-year-old male, suffering from his first spontaneous episode of deep venous thrombosis in the left lower limb. The only defect found in laboratory assays for hemostasis and hepatic function was half normal level of PC, measured by both immunological and functional assays. To confirm congenital PC deficiency, the functional activity levels of PC were compared with those of other vitamin K-dependent factors during stabilized anticoagulant therapy under stable conditions. Although the patient's father had a history of a cerebral vascular accident, his PC level was found to be within normal levels. The patient's mother, free from thromboembolic events, also had a normal PC level. So the patient seemed to be a sporadic case. However, the patient's 14-year-old son, who has been asymptomatic to this time, has the same PC deficiency state.

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Methotrexate (MTX) is frequently used as an antifolatic agent in many malignant neoplasmas such as leukemia, lymphoma and osteosarcoma. The major side effects of MTX are liver and renal damages, bone marrow suppression and so on. But careful management and citrovorum factor resque could decrease the incidence and degree of these side effects. In this report, we described a patient with non-Hodgkin's lymphoma who developed and died of fulminant hepatic failure soon after the administration of intermediate dose MTX. Serological tests for HB virus were not changed throughout, and lymphocyte stimulation test for MTX was strongly positive. His autopsy revealed no inflamatory cell infiltration into the liver, but marked biliary congestion which is a distinctive feature of drug induced hepatitis. From above results, it was suggested that nature of this fulminant hepatic failure was an allergic reaction to MTX. There is no previous report which is concerning about MTX and fetal drug related hepatic failure.

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A 77 year-old male was admitted to the hospital because of lumbago and M-proteinemia. IgA (κ) monoclonal protein (8,100 mg/dl) was demonstrated in serum, and Bence Jones protein (κ) in urine samples. The bone marrow examination showed an increased nunber of pathological plasma cells (34.5%). Multiple osteolytic lesions were evident on X-ray films. A diagnosis of multiple myeloma (MM) was made. He had exudative erythematous skin lesions on his back. His serum was positive for antibody to ATLA. A biopsy specimen from the skin lesions showed Pautrier's micro-abscess which were filled with Leu 3a positive T lymphocytes. 159 base pairs of human T cell leukemia virus I (HTLV-I)/pX position was identified from a cutaneous sample utilizing the polymerase chain reaction method. Thus, a diagnosis of MM superimposed on adult T cell lymphoma was made. An extensive search failed to find any cases complicated with these two diseases except a report by Tagawa et al.¹⁾ concerning a patient with ATL who developed IgA (κ) MM during a five year follow up. Therefore, this is the first reported case of MM superimposed on ATL.

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A spontaneous complete remission was observed in a 47-year-old female with acute monocytic leukemia. Resolution of all abnormalities, including systemic papule, thrombocytopenia, increased numbers of immature monocytoid cells in the peripheral blood and bone marrow, elevation of serum lysozyme and LDH, and trisomy 8 on chromosome analysis, occurred without any treatment. Moreover, the remission was not associated with any infection or blood transfusion, and is persistent for 12-month duration.

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A 29-year-old Japanese male was diagnosed as having autoimmune hemolytic anemia (AIHA) in 1985, and systemic lupus erythematosus (SLE) in 1988. In 1989 a large mass was found of the right posterior area in the liver by computed tomography and ultrasonography. The liver biopsy specimen showed non-Hodgkin lymphoma, diffuse large cell type. No adenopathies or other extranodal involvements were detected. He was treated with five courses of CHOP, followed by involved field irradiation 24Gy. On completion of chemoradiotherapy, the mass was smaller in size with a sign of partial necrosis. Gallium scan was negative suggesting the achievement of a complete remission.
Primary hepatic lymphoma is extremely rare, and its occurrence in patients with AIHA and SLE has not been reported previously. We also review the previously reported cases of primary hepatic lymphoma with respect to its clinical management and ascess the therapeutic strategy of this unusual extranodal lymphoma.

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A 61-year-old male was diagnosed as chronic myelocytic leukemia (CML) in 1985 and had been treated with busulfan for 4 years and 5 months (total 3,572 mg). Since he had complained dyspnea with abnormal lung shadow on a chest x-ray film in May 31 1989, he was treated with 3 mg/day of dexamethasone under a diagnosis of busulfan lung. Dyspnea and lung shadow was remarkably improved after the treatment.
On July 11, he was admitted our hospital with high fever, hypoxemia and diffuse interstitial shadow on a chest x-p. Although intensive treatment with 10 mg/day of dexamethasone and various antibiotics were done, he died in Aug 6. An autopsy revealed the intra-alveolar fibrosis, dense hyaline deposits in alveoli associated with atypical type II epithelial cells in the lung. Seven cases of busulfan lung have been reported in the Japanese literature. The clinical and pathological aspects of these cases, including our case, were discussed.

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Nine adult patients with chronic idiopathic thrombocytopenic purpura (ITP) were treated with ciclosporin. Their platelet counts were all below 5×10⁴/μl.
It was administered orally at 5 mg/kg/day for 8 weeks. In one patient, the platelet count increased over 10×10⁴/μl, in 4 patients it did over 5×10⁴/μl. Gingival hyperplasia was observed in one patient. Renal dysfunction was not observed in any patients. The elevation of PAIgG declined during the period of treatment.
These results suggest that this therapy may be useful in refractory idiopathic thrombocytopenic purpura.

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A 36-year-old man with acute myelogenous leukemia, refractory to the combination chemotherapy, developed fungal infection and acute respiratory distress. Simultaneously, rapid proliferation of leukemic cells was observed in the blood. He was given continuous drip infusion of etoposide (50mg/day) and Ara-C (20mg/day) for 18 days. The leukemic cells desappeared from both the blood and the marrow, and complete remission was achieved. There was no adverse effect related to this therapy. The low dose combination chemotherapy with etoposide and Ara-C is safe to be carried out, and could be effective for the patients with refractory leukemia.

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