Seventy-six carriers of human T-cell leukemia virus type I (HTLV-I), who live in Nagasaki city and its neighborhood, were examined for morphology of peripheral lymphocyte and expression of adult T-cell leukemia-cell-associated antigen (ATLA) in shortterm culture of peripheral mononuclear cells. “Abnormal” lymphocytes with nuclear irregularity such as indentation, convolution and segmentation were observed in 0∼10% (mean, 3.1%) of 100 lymphocytes in 1984. The “abnormal” lymphocytes in this series of subjects ranged between 0∼11% (mean, 2.4%) 2 years before the present study. The percentage of “abnormal” lymphocytes increased in 38 carriers, decreased in 26, and remained unchanged in 12 over the 2-year period.
In 46 (52.6%) of 76 HTLV-I carriers, ATLA was detected. ATLA-positive carriers showed significantly higher frequency of “abnormal” lymphocytes in the peripheral blood than ATLA-negative carriers (mean, 3.8% vs. 2.4%, p<0.05).
Southern blotting analysis revealed monoclonal integration of HTLV-I proviral DNA in 2 and random integration in 10 out of 18 subjects examined, who had high frequency of “abnormal” lymphocytes in the present study. Two subjects with monoclonal integration of HTLV-I provirus appear to have already progressed from HTLV-I carrier to preleukemic state of adult T-cell leukemia (pre-ATL).

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On the basis of countersigmoid curve of tumor regression in experimental model, the equation for leukemic cell kill kinetics during the first induction chemotherapy (logZ=K₁t⁴+K₂t³+K₃t²+K₄Z: leukemic cell number at time t t: time in day K: constant), was composed by computing absolute numbers of leukemic cells per cumm at sternum in 36 previously untreated acute nonlymphocytic leukemia patients. The leukemic cell kill curve was composed from two different phases, phase I and II; phase I corresponding to period from the initiation of decrease of leukemic cells (Point A) to the time of maximum velocity of decrease (Point B), and phase II from Point B to the time of cessation of decrease of leukemic cells (Point C). Determinating coefficients for computed curves were 0.90±0.20 in patients with complete remission (CR) and 0.78±0.36 in patients without CR, respectively.
The parameters for leukemic cell kill curve, i.e, the durations of phase I and II, the accelerations of decrease at Phase I and II, the maximum velocity of decrease, the duration from Point A to C (the duration of phase I plus II) and the residual volume of leukemic cells (leukemic cell number at Point C) were compared among two groups; patients with or without CR. Patients with CR showed the longer duration of phase I and II, the lower acceleration of decrease at Phase II, smaller volume of residual leukemic cells, and the relatively high maximum velocity of decrease, resulting into the cell kill curve showing a relatively sharp at phase I and a gentle slope at phase II. The new equation for leukemic cell kill kinetics in acute leukemia marrow is thought to be available not only for the early evaluation of therapeutic effect but also for the modification of treatment schedule during the induction chemotherapy.

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Twenty-eight years old woman, who had been healthy and had no history of abnormal bleeding, developed wide ecchymoses and intramuscular bleeding 3 months after herfirst delivery.
On admission, the VIII: C was less than 1% and the VIII: C inhibitor (3.8 Bethesda U.) was detected, which consisted of IgG heavy chain and lambda light chain. Furthermore, platelet adhesiveness measured with glass beads column was 1.8%, although vWf activity was 80% in RIPA, 220% in agglutination method and 240 second bleeding time, and vWf: Ag was 245% in Laurell method and showed normal pattern on the crossed immunoelectrophoresis.
The patient was treated with factor VIII concentrate, plasma exchange therapy and steroid therapy. The platelet adhesiveness was normalized soon after steroid therapy. The inhibitor could not be detected also in 6th month.

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We examined anti-ATLA antibody (anti-ATLA) in 77 cases of ATL, 30 AT-ML and 15 Hodgkin's disease in Kagoshima district (ATL endemic area of Japan). Anti-ATLA was detected in all cases (77/77) of ATL, 80% (24/30) of AT-ML and 53% (8/15) of Hodgkin's disease.
In ATL, ATLA was detected in 71% (12/17) (geometric mean titer of antiATLA: 24.5) and HTLV-1 proviral DNA in all cases (13/13). In AT-ML with anti-ATLA, ATLA was detected in 86% (6/7) (geometric mean titer of anti-ATLA: 53.8) and HTLV-1 proviral DNA in all cases (5/5). HTLV-1 proviral DNA was examined in one case of AT-ML without anti-ATLA. In this case, HTLV-1 proviral DNA was demonstrated.
We examined ATLA in only one case of Hodgkin's disease with anti-ATLA. In this case, ATLA was detected, but HTLV-1 proviral DNA was not detected.
The detection of HTLV-1 proviral DNA was useful the diagnosis of lymphoproliferative disease, especially, adult T-cell leukemia-lymphoma in the endemic area of HTLV-1.

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A microplate enzyme linked immunosorbent assay (ELISA) has been developed for quantitation of small amount of red blood cell-bound IgG from hematologically normal subjects. A double antibody sandwich method used in this study was highly sensitive and reproducible. The number of IgG molecules bound to a normal red cell was ranged from 15 to 104 with an average of 55 (N=30). Because contamination of buffy coat provides a high titer (false positive result), it is important to remove buffy coat as completely as possible by repeated washing of red cells.

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A phase III study of mitoxantrone (MIT) in acute leukemia was conducted by the Tokai Blood Cancer Study Group between February, 1983 and April, 1985.
The study involved 53 patients with adequate renal and hepatic function and aging under 70 years old.
Twenty seven patients with acute nonlymphocytic leukemia (ANLL) and four patients with myeloid crisis of chronic myelogenous leukemia (CML) were treated with MIT in combination with behenoyl cytosine arabinoside, 6-MP and prednisolone (BHAC-MMP). As to ANLL, 7 of 8 patients in first induction, 3 of 4 in primarily refractory, 8 of 11 in relapse and 2 of 4 in relapse and refractory achieved complete remission (CR), respectively. Two of four patients with myeloid crisis of CML achieved CR. The disease free survival rate of CR cases with ANLL achieved at the first induction was 42% at 70 weeks after initiation of treatment and that at the reinduction was 28%, respectively. Twenty patients with acute lymphocytic leukemia (ALL) and two patients with lymphoid crisis of CML were treated with MIT in combination with vincristine sulfate and prednisolone (MVP). As to ALL, 8 of 8 patients in first induction, 3 of 4 in primarily refractory, 4 of 5 in relapse and 1 of 3 in relapse and refractory achieved CR, respectively. None of 2 patients with lymphoid crisis of CML achieved CR. The disease free survival rate of CR cases with ALL achieved at the first induction was 38% at 40 weeks after initiation of treatment and that at the reinduction was 13%, respectively.
The present regimen, however, results in a more prolonged duration of leukopenia than that of thrombocytopenia. So, infectious complications happened rather frequently such as sepsis in 23% with BHAC-MMP regimen and 18% with MVP regimen. Side effects included anorexia, alopecia, nausea and vomiting, hepatic dysfunction and stomatitis, but no significant cardiac toxicity occurred in this study.
These studies suggest that MIT in combination with other drugs is of high value in the treatment of patients with acute leukemia.

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A 52-year-old male was admitted to our hospital with chief complaint of jaundice. On admission, anemia and hepatomegaly was detected. Laboratory findings included normochromic anemia, hyperbilirubinemia with predominant indirect bilirubin and markedly increased urinary urobilinogen. In peripheral blood, about 5% myeloblast-like cells were observed.
Enzymatic analyses of red blood cells showed reduced pyruvate kinase (PK) activity. But the patient's sister, two brothers and two daughters showed normal PK activity.
According to the recommendation of the International Committee for Standardization in Haematology (ICSH), this abnormal PK variant was named PK Matsumoto.

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A case of hairy cell leukemia (HCL) with atypical features such as no splenomegaly, no pancytopenia, and L-tartarate sensitive acid phosphatase activity of the hairy cell (HC) is presented. The HC had a morphology of a medium sized lymphoid cell with a wide and irregular lace-like surfaced cytoplasm, and phase contrast microscopically had elongated hairy projections and bizzare pseudopods. The surface marker analysis showed that the HC had receptors for the Fc of IgG and IgM, and for the mouse complement, and had multiple heavy chains (γ, μ, and δ) and a monoclonal light chain (κ) on its surface. And by the analysis with monoclonal antibodies such as anti Leu 1, anti Leu 4, anti Leu 2a, anti Leu 3a, anti Leu 12, anti Leu M1, anti HLA-DR, anti B1, anti B2, and anti J5, the HC had a typical B cell phenotype (positive for Leu 12, B1, B2, and HLA-DR), but after 3 or 4 days culture the HC expressed Leu 1 and Leu M1. About the effects of 12-o-tetradecanoyl phorbol-13-acetate (TPA) on HC, only the morphological changes as found in chronic lymphocytic leukemia (CLL) were reported. The marked expression of Leu 1 and the morphological changes as reported in CLL were found in HC of this case treated with TPA. These results may show the close relationship of HCL and CLL (including CLL related Leu 1 positive B cell malignancy).

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A 55 year-old-woman was admitted to our hospital with complaints of high fever and back pain in April, 1983. One year prior to admission she was treated as Ph¹ positive CML with myelofibrosis.
By physical examination and laboratory findings, she was suspected of blastic phase of CML. After treatment with ACNU and DBM, she suffered for severe bone marrow hypoplasia for 3 months. Although she complicated with candidiosis of spleen and liver, she entered in complete remission lasting one year. During that time, chromosome analysis of bone marrow revealed marked reduction of Ph¹ positive cells. In August, 1984, she died of systemic fungal infection with DIC.
Autopsy findings revealed mild myelofibrosis but no evidence of extramedullary hemopoiesis. This case was diagnosed as atypical myeloploliferative disorder.

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A 20 year old woman suffering from hemolytic anemia was admitted to our hospital because of exacerbated hemolysis after EB virus infection. Laboratory data were compatible to unstable hemoglobin hemolytic anemia and cellulose acetate membrane electrophoresis (pH 8.6) showed abnormal band between Hb A and Hb A₂. PCMB treatment of hemolysate caused massive yellow-white colored precipitate, most of which was identified to be composed of β-chain by isoelectric focusing. Although tryptic fingerprinting of aminoethylated abnormal β-chain showed no abnormality, amino acid analysis of each peptide extracted from the tryptic fingerprint revealed the substitution of valine to methionine in βTp-11 and identified to Hb Köln or β 98 (FG 5) Val→Met. Functional analysis of abnormal hemoglobin by OEC showed the increased oxygen affinity and the decreased subunit co-operativity. In family study, this hemoglobin was also found in mother, uncle and two cousins, suggesting that it was inherited by autosomal dominant trait. We reported here the tenth case of Hb Köln found in Japan.

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A 1 10/12 year-old boy with Down's syndrome (DS) was admitted to the Saitama Children's Medical Center with anemia and petechiae in March, 1982. On admission physical examination showed the presence of hepatosplenomegaly and systolic heart murmur. His hemoglobin was 9.9 g/dl, platelet count 4.6×10⁹/l and white blood cell 3.7×10⁹/l with 6% blasts. He was diagnosed as having refractory anemia with excess of blasts according to FAB classification. Chromosome analysis of cells from bone marrow revealed 48, XY, +11, -15, +21, +der(15)t(1;15)(q25;p11). Subsequent follow-up without chemotherapy showed no consistent change. In September, however, leukemic cells increased to 70% in the bone marrow. The blasts were negative for peroxidase, periodic acid-Shiff, α-naphtyl acetate esterase and α-naphtyl butylate esterase, positive for acid phosphatase stainings. About 70% of blasts were shown to posses platelet peroxidase on electron microscopic study. Cell marker studies using KOR-P77, which is monoclonal antibody to the platelets, showed to be positive, He was diagnosed as having acute megakaryoblastic leukemia (AMkL, M7 of FAB). He was treated with aclarubicin and enocitabin, and obtained complete remission. After 3 courses of this regimen he relapsed and died of pneumonia.
AMkLs with DS in the literature were discussed. A trisomic for a long arm of chromosome 1 in this case, which has been frequently reported in solid tumors, has been described in 5 cases with acute leukemia and Down's syndrome. We considered that addition of no. 21. chromosome was associated with leukemogenesis of AMkL.

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We present a case of 50 year-old woman with giant hemangioma of the whole right lobe of the liver, with abnormalities of the hemostatic system characteristic of disseminated intrascular coagulation. The presence of giant hemangioma of the liver was confirmed by means of CT scanning of the abdomen and the selective arteriography of the liver via superior mesenteric artery. Following treatmnet with continuous I.V. heparin infusion, abnormal hemostatic values were corrected, which included a rise in fibrinogen, Factor V, and VIII levels, and platelet counts. When the heparin treatment was discontinued, the consumption coagulopathy with secondary fibrinolysis developed again. Removal of the liver hemangioma completely normalized the alterations of the clotting system.

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We report a case of acute myelofibrosis (AMF), whose bone marrow fibrosis had almost disappeared on autopsy following chemotherapy. Fourty five-year-old male was admitted to Jichi Medical School Hospital on April 2, 1983, because of fever and a tumor in his left hip. He was diagnosed as having AMF by the following clinicopathologic manifestations; rapidly progressive pancytopenia, a few blasts in peripheral blood identified as megakaryocytic series by the platelet peroxidase reaction (PPO), absence of abnormal red cell morphology, lack of splenomegaly, and diffuse bone marrow fibrosis with relative proliferation of atypical immature megakaryocytic cells on bone marrow biopsy. the tumor in his hip was histologically identified as inflammatory reaction without atypical cells.
He was treated with cytosine arabinoside and daunorubicin. After 20 days, diminution of bone marrow fibrosis and disappearance of atypical immature megakaryocytic cells was observed on bone marrow biopsy. However, the patient did not obtain hematological improvement, and died on June 13, 1983.
Post-mortem examination disclosed that there were no extramedullary hematopoietic foci and atypical cells in the liver (2,070 g) and spleen (230 g), marked diminution of bone marrow fibrosis and disappearance of atypical immature megakaryocytic cells, suggesting that bone marrow fibrosis of AMF is reversible following chemotherapy.

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A 34-year-old woman who presented with intraperitoneal hemorrhage caused by factor VIII inhibitor which developed after her third normal delivery was reported.
She had no previous personal or familial history of any abnormal bleeding. On admission with complaints of ecchymoses, gingival bleeding, and joint swelling, her labolatory examination showed a marked prolonged partial thromboplastin time and a low level of factor VII activity (1.7%). Further study revealed that her serum had a factor VIII inhibitor and its titer was as high as 950 Bethasda units/ml. The charcterization of this inhibitor was as follows; it was eluted at 7S globulin peak in gel filtration with Sephadex G-200, and neutralized with anti-IgG, anti-kappa chain and anti-IgG₃ or anti-IgG₄ antibodies. it was ‘Type II antibody’ according to the classification by Biggs et al.
She was treated with double filtration plasmapheresis and was given a combination therapy of prednisolone 50 mg/day and cyclophosphamide 100 mg/day with disappearance of bleeding tendency. But with her menstruation she was complainted with anemia and abdominal distention which were attributed to the intraperitoneal hemorrhage from the extra-endometrium of an ovary and Douglas, cul-de-sac on laparotomy. Proplex was administered with improvement. Two months later, factor VIII inhibitor was no longer detected and she was discharged.

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A 78-year-old male presented with splenomegaly. Leukocyte count was 15,700/μl (abnormal lymphocyte 22%), and bone marrow was normocellular (abnormal lymphocyte 10.75%). Cytochemistry revealed peroxidase negative, acid phosphatase (AP) positive, tartrate resistant AP negative. Analysis of cell surface markers revealed OKT3^-, OKT9⁺, OKT10⁺, Ial⁺, B1⁺, J5⁺, M1⁺, s^-Ig^- and Fcγ⁺, The abnormal lymphocytes were larger than those of CLL and PLL; ultrastructural mean diameter being 9.7 μm. They had ruffled membranes, many long villi and zipper-like structures. Ribosome-lamellar complex was not observed. Negativity for surface immunoglobulin and positivity for common ALL antigen were distinct from ordinary characteristics of surface markers of HCL cells. From these and ultrastructural findings, it was suggested that the abnormal lymphocytes of this case was committed in the immature B-lymphocyte near pre-B cell. Zipper-like structure has been already reported in HCL cells. It should be further investigated whether this structure is specific to HCL.

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A 47-year-old man having a chronic liver disease developed uncontrollable bleeding which was due to an inhibitor to factor XIII (F.XIII). The inhibitor was demonstrated by ready solubility in 2% monochloroacetic acid of the fibrin clot obtained from the mixture of normal and the patient plasma, and by absence of gamma-dimer and alpha-polymers in SDS-polyacrylamide gel electrophoresis of the clot. The inhibitor suppressed the transamidase activity of activated F.XIII and did not affect the activation of F.XIII by thrombin. A neutralization test showed that the inhibitor was an antibody of polyclonal IgG, and isolated IgG from the patient plasma exhibited the inhibitor activity. The patient plasma contained almost normal levels of F.XIII a and b subunit antigens, and Sephadex G-200 gel filtration of the plasma revealed that there was intact F.XIII separable from the inhibitor. These findings were interpreted that the inhibitor interacts not with the zymogen form but with the activated form of F.XIII.
These have been ten fully documented cases of inhibitor to F.XIII. Many of them had been treated with isoniazid, which is consequently thought to be related to the generation of the inhibitor. Our patient had not received such a drug and the cause is unknown.

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A 2-year-old boy was admitted to Tokushima University Hospital because of pallor in January 1984. The diagnosis of transient erythroblastopenia of childhood was made from severe microcytic anemia, reticulocytopenia and erythroblastopenia. Spontaneous recovery was seen about one week after initial diagnosis, without corticosteroid therapy.
In order to determine the mechanism of anemia, we evaluated the marrow cell erythropoiesis in vitro and its effect of the serum. The number of burst-forming units-erythroid (BFU-E) in the bone marrow of the patients was increased and become normal at recovery. The patient's serum at initial stage suppressed the growth of normal and patient's BFU-E and the suppression was no longer present after the erythroblastopenia had remitted. These findings suggest the transient immune suppression of erythroid colony development.

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Fifty six (56) chronic ITP cases were treated with steroid hormone over one year and the effectiveness of steroid was evaluated. Fourty one cases (66.1%) showed good response (platelet counts≥10×10⁴/μl) to the initial steroid treatment within 15∼80 days (mean 29.4 days) and the platelet counts increased depend on cumulative dose of steroids (prednisolone, β-methasone). The clinical and hematological responsiveness after at least one year of steroid treatment was observed in 9 cases were complete remission (platelets≥10×10⁴/μl) reaching to the drug free, in 18 cases of partial remission (Plts≥10×10⁴/μl), 10 cases of minor response (5×10⁴≤Plts 10×10⁴/μl) and 19 cases of non responder (plts<5×10⁴/μl). The CR and PR groups showed good response to initial therapy and the pretreatment period from the onset was shorter than that of MR or NR. Since there was no remarkable correlation between the clinical response to steroid and the PAIgG level or other various autoantibodies level, the prediction of steroid responsiveness before treatment was difficult by these serological findings. The complications of steroid therapy were found in steroid unresponsive cases who were treated with large amount of steroid for long period.
These analysis mentioned that the prednisolone (β-methasone) treatment should be the first choice for the initial treatment of ITP to relieve bleeding tendency and to increase the platelet counts rapidly in above half cases (48%).

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During the past thirteen years (from July 1971 to June 1984) 89 patients with chronic idiopathic thrombocytopenic purpura, including 3 cases of Evans' syndrome, were treated in our clinic. In all cases, diagnosis was confirmed by laboratory tests including platelet kinetics with ⁵¹Cr. Treatment was started with prednisolone 1 mg/kg body weight/day and 12 cases attained remission. In 25 cases out of 38 platelet counts were maintained above 100×10³/μl and one case above 70×10³/μl without therapy from 17 to 146 months after splenectomy. Favorable factors to splenectomy were as follows: younger age especially under 30, spleen dominant pattern in surface counting, prolonged platelet life span after splenectomy and small number of foam cells in spleen. Duration of the illness, initial response to steroid and platelet life span before splenectomy were equivocal.
Importance of longtime followup of the splenectomized patients was emphasized.

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A multicenter co-operative study was performed to assess the efficacy of danazol in chronic refractory idiopathic thrombocytopenic purpura. Seventy-one patients were included in this study. Twenty-four of 57 evaluable patients were benefited from danazol, 10 with excellent response and 14 with good response. The platelet count started to increase within two weeks of the therapy in most of responding patients, but it tended to decrease after discontinuance of administration. Response to the danazol therapy could not be predicted from the result of the previous therapy. Side effects such as liver injury, androgenic effects, hypoestrogenic symptoms and skin rash occurred in as many as 82% of patients, which, however, were generally mild and promptly improved after withdrawal of the drug.
The observation in mice showed that danazol accelerated the platelet production, and that it inhibited the clearance of immune-injured platelets from circulation. Both of these mechanisms may explain the clinical effect of danazol in patients with idiopathic thrombocytopenic purpura.

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Preparations of intact immunoglobulins, one sulfonated (Veniron®) and two polyethyleneglycoltreated (Venoglobulin-I® and Glovenin-I®) were administered intravenously in high doses respectively to 177, 303 and 134 patients with idiopathic thrombocytopenic purpura (ITP). Regardless of their responsiveness to adrenocorticosteroids, most patients showed a favorable rise of platelet count. The most effective dose was 400 mg/kg daily for 5 consecutive days. In most cases of acute ITP rise in platelet count was maintained, but in most cases of chronic ITP it was transient. A few cases showed mild and transient side-effects.
High-dose immunoglobulin therapy is indicated especially in cases with severe bleeding tendensies, and in patients facing surgery or delivery. Because it is expensive, however, it should be restricted to cases in which adrenocoticosteroid or immunosuppressant therapy produces no platelet elevation.

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32 of 125 children with newly diagnosed ITP who exhibited marked hemorrhagic manifestations within a week of onset were treated with oral prednisolone (PSL, 13 cases), intravenous immunoglobulin (IVIg, 12 cases) and “Pulse” methylprednisolone (m-PSL “Pulse”, 7 cases). The number of the patients who responded well to these treatment were 10 (77%), 11 (92%) and 5 (71%), respectively. The mean periods in which platelet counts of these patients achieved appreciable elevation (10×10⁴/μl) were 2.6±0.8 day in IVIg, 4.0±0.6 day in m-PSL “Pulse” and 11.9±5.5 day in conventional oral PSL therapy (p<0.001). There was no significant difference in a rate of platelet increase between the casses with oral PSL and those with no treatment, as a whole.
57 of 130 children with chronic ITP investigated by Idiopathic Disorders of Hematopoietic Organ Research Comittee, The Ministry of Health and Welfare of Japan were initially treated with oral PSL at the doses of 1 mg/kg or 2 mg/kg for at least two weeks. Although 23 of 54 patients manifested favorable reaction on this therapy with at least 5×10⁴/μl of platelet increment, they had a tendency to develop thrombocytopenia again along with tapering of PSL except for 8 (14%) patients. 43 of 130 patients were undergone splenectomy in recent 15 years, and they obtained a beneficial response in 29 (67.4%) cases and a relief from hemorrhagic manifestation in 39 (90.7%) cases during long-term follow up studies of 2 to 15 years. On the contrary, in remaining 87 non-splenectomized patients the incidence of reversal of thrombocytopenia was 40.2% and 22 cases were still dependent upon PSL or immunosuppressive regimens. Twenty one patients with steroid-dependent chronic ITP were treated with IVIg and m-PSL “Pulse” which resulted in favorite but transient rise in platelet count. 3 of 17 cases who were treated with IVIg showed so-called long-term response.
From these data it is postulated that IVIg treatment is a most reliable therapeutic measure in the management of acute ITP with severe hemorrhagic manifestation, and in chronic ITP there appears to be no more satisfactory alternative to splenectomy at present.

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In order to delineate the clinical aspects relating to “intractable” nature of ITP, our experience on 154 cases was analyzed. The patient population showed following characteristics; average onset-age of 35 years, ranging 0∼79, male/female ratio of 43/111, acute/chronic form of 24/126 with 4 unclassified. 35 cases were observed without receiving any standard forms of therapy, and the remainder was managed by relatively modest treatment including splenectomy in 14 cases. Patients were followed for 5 years on average. There were 13 deaths (8.4%), of which 6 were directly related to bleeding and 5 were to complications and 2 were ascribable to unrelated causes. Initial severe thrombocytopenia was a significant prognostic variable. The increment of platelets during the follow-up was less than 50×10⁸/μl in 46% of cases, while platelet count at the last observation remained less than 50×10⁸/μl in 33% of cases. 17% of cases with chronic ITP suffered from mild bleeding tendency at the last follow-up. However, the activity in daily life was maintained reasonably well in the majority of cases. In addition, the disease process appeared to subside gradually to give a stable platelet count above 100×10³/μl in 40% of chronic form. For practical management of patients, all these aspects should be taken into account.

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A long term prognosis of 248 patients with ITP was analysed. A complete remission was observed in 53 of 62 patients with acute ITP (85.4%), 45 of 127 cases of chronic ITP (35.4%) and 35 of 59 splenectomized patients (59.3%).
The period between the onset of disease and the remission was 5 months, 7.2 years and 5.0 years (1 year after splenectomy) on the average in acute ITP, chronic ITP and splenectomized patients respectively.
Fifteen cases inclusive of 8 cases of SLE and 3 cases of aplastic anemia, were diagnosed as ITP at the first examination. Two cases of SLE received splenectomy in 4 months and 1 year after seeing doctor at the first time.
An intracranial bleeding leads to death in 7 of 8 deceased cases in acute ITP and bleeding in other sites of body was a cause of death in chronic ITP.
A prediction of the therapeutic effects in 70 cases which had complete data of 6 factors as the dose of steroid hormons given according to the first medication, the type of ITP, age of patients, years betweenen the onset of disease and the first examination, was maede using a numerical method of class II. 76.9% of cases obtained complete remission was predictable as effective after the first treatment.
Further analysis is needed using many more patients and it seems to be necessary to review the factors for analysis.

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The hematological features and prognosis of 264 patients with refractory myelodysplastic anemias were reported. They were classified according to a uniform diagnostic criteria into 3 types; primary acquired refractory anemia (PARA, 111 cases), primary acquired sideroblastic anemia (PASA, 49 cases) and refractory anemia with excess of blasts (RAEB, 104 cases). They were ranged between 15 and 85 years of age with a median of 59 years. Male to female ratio was 1.9: 1. Peripheral cytopenias, mostly in the form of pancytopenia and bicytopenia, cellular marrow and a variety of dysplastic morphology represented major hematological findings. In addition, ineffective erythropoiesis was most prominently seen in patients with PASA. Leukemic transformation was most frequently seen in RAEB, least common in PASA. Thus, leukemia-free rate was estimated to be 60% in the whole patients; 28.9% in RAEB, 74.5% in PARA and 89.6% in PASA. The median survival from presentation was 15.8 months in RAEB, 42.6 months in PARA and 40.4 months in PASA. The blast cell count in the marrow was the most significantly variable high leukemic risk and short survival. Among the dyshematopoietic morphology, dysgranulopoietic changes, especially abnormal granules, and dysmegakaryopoietic changes, notably giant platelets and mononuclear megakaryocytes, were also related to poor prognosis. Even in the absence of leukemic transformation, certain complications such as infections and/or bleeding, resulting from persistent cytopenias were frequent causes of death. The results point to a need for a more careful management of patients in the chronic phase.

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Ninety-nine patients with myelodysplastic syndrome (MDS) were analysed to determine the significance of morphological aspects of dysmyelopoiesis and the affects of dysmyelopoiesis on prognosis. For subtyping MDS, FAB criteria (Bennett et al. 1982) was applied. For refractory anemia (RA) the following diagnostic criteria was used: persistent unexplained anemia with Hb concentration less than 11 g/dl and normo-or hyper-cellular marrow. Obeying FAB criteria, the following morphological abnormalities were evaluated to represent dysmyelopoiesis: ‘dyserythropoiesis’ (megaloblastic changes, multinuclearity, abnormalities in the nuclear shape, nuclear fragments, ring sideroblasts), ‘dysgranulopoiesis’ (Pelgar-Huet type nuclei, markedly hypogranular PMN, ring nuclei, hypersegmentation of 6 or more segments), and ‘dysmegakaryopoiesis’ (micromegakaryocytes, round mononuclear megakaryocytes and megakaryocytes with separated multiple nuclei). Two hundred erythroblasts, 200 granulocytes and 25, if possible, megakaryocytes were counted and the results were reported as percentages of cells showing abnomalities, In order to determine whether the dysplastic changes are specific to MDS or not, we also examined the bone marrows from normal subjects and patients with autoimmune hemolytic anemia (AIHA), iron deficiency anemia (IDA), and aplastic anemia (AA). The following results were obtained:
1) The number of patients with MDS subtypes was as follows: RA 49, RA with ring sideroblasts 5, RA with excess of blasts (RAEB) 20, RAEB in transformation (RAEB in T) 22, MDS with myelofibrosis 3.
2) The rates of leukemic transformation were 12.2%, 40.0%, 55.0% in RA, RAEB, RAEBin T respectively.
3) The analysis of Kaplan-Meier survival curves revealed that the patients with RA had good prognosis and the patients with RAEB or RAEB in T had bad prognosis. The 50% survival of RAEB and RAEB in T were 12.5 and 14.3 months respectively.
4) Slight degree of dyserythropoesis or dysmegakaryopoiesis was occasional seen in a minority of normal subjects and some patients with IDA or AA, but dysgranulopoiesis was only seen in the patients with MDS.
5) The analysis of Kaplan-Meier survival curves revealed the presence of dysmyelopoiesis (>5% dyserythroblasts, >5% dysmegakaryocytes, ≥0.5% dysgranulocytes) to be a sign of bad prognosis.
6) The complication of myelofibrosis in patients with MDS made duration of survival very short. All patients terminated in acute leukemia, in which some leukemic cells were identified as megakaryoblasts.
7) Two cases of typical aplastic anemia were turned to MDS with cellular marrow and dysgranulopoiesis.
8) RA consists of a wide range of disease from cases indistinguishable form mild AA to cases close to RAEB.

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Cytogentic studies in patients with myelodysplastic syndrome (MDS) were performed at the time of diagnosis, during the course of the disease and at the time of leukemia, as well as the examination of sister chromatic exchange rate in bone marrow cells, unscheduled DNA repair activity and DNA transfection activity.
Complexed type of chromosome aberrations were observed more frequently in patients with refractory anemia with excess of blasts (RAEB) than those in patients with primary acquired refractory anemia (PARA). Increased sister chromatid exchange frequency in the bone marrow cells of MDS and deficient in repair of UV-induced lesions by DNA, irrespective of the presence or absence of a karyotype abnormality were clearly demonstrated. Transfection of DNA from bone marrow cells with MDS into NIH 3T3 cells showed no focus formations.
From these results, difference of patho-physiology between RAEB and leukemia was discussed.

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The clinicopathologic findings of 24 autopsy cases of the myelodysplastic syndromes (MDS) including 8 cases of the refractory anemia with excess of blasts (RAEB), 4 cases of the RAEB in Transformation (RAEB in T), 3 cases of the refractory anemia, 5 cases of the chronic myelomonocytic leukemia and the other 3 cases were reported.
The conclusions in this study were followings:
(1) The RAEB was characteristic myeloproliferative state and there were seven of eight cases which terminated in overt leukemia.
(2) The leukemia with MDS showed characteristic autopsy findings compared with typical acute non-lymphocytic leukemia.
(3) It was difficult that we expected the outcome of the disease by the only histological findings of bone marrow in early stage.
(4) It was considered that the RAEB in T had more neoplastic nature.
(5) In the cases with hypoplastic bone marrow, there were some cases which had marked morphologic dysplasia in various hemopoietic cells.
(6) Cytochemical stains, immunohistochemical study and electron microscopic observation are necessary to identify the blasts and variegated morpholigic abnormality of hemopoietic cells.

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Previously, wereported that patients with monocytic leukemia had a polyclonal hypergammaglobulinemia. Serum γ globulin levels may be useful parameter for diagnosis of the subtypes of leukemias and also for pathological activity of leukemia during clinical course. However, the pathogenesis of hypergammaglobulinemia is not clear. Present study was undertaken to elucidate the mechaism(s) of hypergammaglobulinemia in patients with monocytic leukemia. The circulating monoblasts or monocytes from patients with acute monocytic leukemia, acute myelomonocytic leukemia, or chronic myelomonocytic leukemic were used in this study. When leukemic monocytes were co-cultured with nonadherent cells obtained from healthy subjects, Ig production was significantly augumented compared to those in normal monocytes or medium alone. Irradiated leukemic cells revealed the enhancing effect of Ig production, while heat Killed cells completely lost the activity. In the culture supernatants from leukemic monocytes, both the enhancing effect of Ig production and interleukin 1 like activity were found. It has been suggested that leukemic monocytes factor does not act by stimulation of helper T cells, but doesdirectly on the B cells to differentiate to Ig secreting cells.
Chromatography of culture supernatants on Sephadex G-100 revealed the enhancing activity of Ig production with M, W, from 5,000 to 50,000 daltons.
We conclude that live, intact leukemic monocytes produce IL-I like factor which stimulate B cell differentiation to Ig secreting cells.

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We have examined ferritin levels in the serum and red blood cell in patients with myelodysplastic syndrome (MDS), especially in those with refractory anemia (RA). The results are as follows:
1) A high acidic ferritin level in the serum of patients with MDS appeared to correlate to an accelerated onset of overt leukemia and a shortened survival time, according to the analysis of data at the first medical examination of 29 cases with MDS by multivariate analysis (Hayashi).
2) A higher ferritin level in the acidic form than in the basic form was observed in the serum of patients with RA.
3) Serum feritin level in patients with RA was more acidic than that in patients with blood transfusions, when determined by an isoelectric focusing method.
4) Serum ferritin in patients with RA showed greater binding capacity to Con A than did that in iron-overloaded patients.
5) Ferritin level in the red blood cell in patients with RA and primary aquired refractory anemia (PARA) well correlated to serum ferritin level, when determined by a R-PHA method, but not by a IR MA method.

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