Red blood cell autoantibodies were analyzed by antiglobulin tests using monospecific antisera to IgG, C_3d or C_3bd C₄ in 19 cases of autoimmune hemolytic anemia (AIHA).
In the Evans' syndrome, platelet-associated IgG (PAIgG) as well as red blood cell autoantibodies were measured by means of complement lysis inhibition assay. Autoantibodies bound to the patients' RBC in 9 cases of 13 uncompensated AIHA were found to be IgG and C_3d. When the AIHA patients having the RBC autoantibodies of IgG plus complement components were treated by glucocorticoids, immunosuppressants or irradiation therapy, the C_3d bound to the patients' RBC disappeared firstly as the increased hemolysis was gradually improved, and then the IgG autoantibodies bound to the patients' RBC reduced to vanish. These results apparently indicate that the increased hemolysis in AIHA is caused by autoantibodies to RBC consisting of IgG plus complement components. The PAIgG was increased from 35.1±16.7 ng/10⁷ platelets to 142∼202 ng/10⁷ platelets in three cases of Evans' syndrome, which RBC was bound by IgG and C_3d. Based on these findings, it is suggested that the thrombocytopenia is caused by antiplatelet autoantibodies and the increased hemolysis is caused by RBC autoantibodies consisting of IgG and complement components in Evans' syndrome.

View full abstract

Long-term prognosis was investigated in 139 children with acute lymphoblastic leukemia (ALL) who had been in complete remission for longer than three years.
Thirty five of these children (25.2%) relapsed three years later, and the relapse-free survival (RFS) was estimated 68.5% at 10 years by Kaplan-Meier method. Sites of relapse were bone marrow (BM) in 21, central nervous system (CNS) in 9, testis in 3, and BM and CNS, simultaneously in 2. Twenty five of 35 relapse (71%) occurred during the first year after the three years complete remission. There was no relapse beyond seven years after the onset.
Age or white blood cell counts which is the major prognostic factor at the time of diagnosis, was of no value in predicting the late relapse. However, boys or children with low initial platelet counts (<100,000/mm³), had significantly poorer long-term RFS.
The late relapse was more frequently occurred in the patients treated with 721 Studies consisting of only three intrathecal injection of MTX for CNS prophylaxis and relatively small doses of MTX and 6-MP for maintenance therapy. Prolongation of treatment after three years was no benefit to prevent the late relapse (RFS 53.9% for 3-year treatment, 53.4% for 4-year, 61.2% for 5-year).
These data suggested that early cytoreductive treatment with three or more drugs should be employed for all patients at least within three years. Further studies are necessary to evaluate duration of therapy, especially for boys.

View full abstract

Flow cytometric analysis of the bone marrow cellular DNA content was performed in 23 adult patients with acute leukemia. We investigated in this study the relationship between the cell kinetics of bone marrow cells before therapy and the effect of chemotherapy and also the prognosis. The results were summarized as follows.
1) For the whole seresis, the G₁/G₀ phase compartment was 78.8±8.6% (Mean±SD), the S-phase compartment was 15.9±8.1%, the G₂+M-phase compartment was 5.3±2.5%.
2) The patients in relapse had lower percentage of S-phase compartment that observed before the initial therapy.
3) The patients with acute nonlymphoblastic leukemia who obtained complete remission had significantly higher percentage of S-phase compartment than that in those who did not. (p<0.05).
4) There was a tendency that the cases with the higher percentage of S-phase compartment had the shorter term to complete remission.
5) In the patients who obtained complete remission, the patients with lower percentage of S-phase compartment at pretreatment had longer remission duration and survival, compared to patients with higher values.
The results of this study suggests that the percentage of bone marrow leukemic cells in S-phase in previosuly untreated acute leukemia is one of predictive parameters for the prognosis and aids us in selecting chemotherapy.

View full abstract

Vinca-alcaloid (V-A) was given in slow infusion to six adult patients with refractory idiopathic thrombocytopenic purpura (ITP), including 5 were unresponsive to glucocorticoids, and one who was unresponsive to danazol. Vincristine, 0.02 mg/kg or vinblastine 0.1 mg/kg, was dissolved in 500 ml of isotonic saline and infused intravenouslty over 6 hours.
The mean platelet count of the patients on study was 2.18±1.3 (×10⁴/mm³), which rose to 6.8±3.7 (×10⁴/mm³) to 7.8±4.4 (×10⁴/mm³), to 11.2±6.6 (×10⁴/mm³) and to 14.9±5.1 (×10⁴/mm³), 1, 4, 8 and 15 weeks after the begnining of therapy, respectively. Side effects, including mild neuropathy, constipation, alopecia, and leukopenia were common on V-A slow infusion, but were decreased by the reduction of dose of V-A, except severe neuropathy in one patient who needed the cessation of therapy.
These findings indicated that Vinca-alkaloid slow infusion therapy is effective and tolerable to the patients with refractory ITP.

View full abstract

In order to explore the problems on treatment of Hodgkin's disease in Japan, we studied seventy patients who were diagnosed and treated as having Hodgkin's disease at Nihon University Hospital, Chiba Cancer Center and Saitama Cancer Center between August 1974 and April 1985. All the biopsied materials were reviewed and the diagnosis of Hodgkin's disease were confirmed in fity four cases by two pathologists, who were members of the Lymphoma Study Group in Japan. Pathological classification and staging were reviewed on these 54 cases. Therapy and survival were studied retrospectivly on 52 treated patients. The conclusions were as follows:
(1) Although nodular sclerosis of Hodgkin's disease is less common in Japan than in the United States, low incidence of this type could not explain the poor therapeutic results in Japan.
(2) Results of treatment for Hodgkin's disease with stage I-II were not acceptable. Proper radiotherapy with or without chemotherapy, based on accurate diagnosis for extension of the disease by the precise staging procedures including lymphography and whole body CT should improve the prognosis of early stage Hodgkin's disease.
(3) Since original MOPP therapy cannot be administer to the patients in Japan, intensive combination chemotherapy including Adriamycin would be recommended for treatment of Hodgkin's disease in stage III or IV.
(4) It is important to set up a standard therapy for Hodgkin's disease in Japan.

View full abstract

In this paper, clinical and hematological findings of 4 patients showing myelodysplasia with hypoplastic marrow (Group A) were compared with those of 8 patients diagnosed to be myelodysplastic syndromes (MDS) according to FAB classification (Group B). Cytopenia and morphological anomalies in 2 or 3 blood cell lines, corresponding to hematological characteristics of MDS, were found in all patients in Group A.
The results included followings; (1) Age distribution in Group A and B showed no significant difference. Male and female ratio was 5: 3 in Group B. On the other hand, all were male in Group A. The interval between the onset of initial symptom and diagnosis tended to be longer in Group A than that in Group B (9 vs 5.5 months in median). (2) In Group B, 5 patients were classified as RAEB and 3 patients as RAEB-T according to FAB criteria. In Group A, hematological findings were similar to RAEB in all patients except for hypoplastic marrow. Although the degree of anemia was at most equal in both groups, leukocytopenia and thrombocytopenia were somewhat more severe in Group B. (3) During the clinical observation, one patient terminated in acute leukemia (M₂) in Group A and B, respectively. A clonological change, hypoplastic to hyperplastic marrow, was observed in one patient in Group A. The median survivals from the onset of initial symptom and from the diagnosis were 23.5+ and 14+ months, respectively. On the other hand, they were 10+ and 6+ months in Group B. The study on clinical and hematological findings could not disclose significant differences between Group A and B except the slightly longer survival in Group A.
Although myelodysplasia with hypoplastic marrow is excluded from MDS because of its hypoplastic marrow, they may be essentially the same entity, particularly in respect to hematological disorders preceding the onset of acute leukemia.

View full abstract

The effect of anthracyclines on cardiac function was assessed by left ventricular ejection fraction (LVEF), peak ejection rate (PER) and peak filling rate (PFR), which were measured by using radionuclide angiocardiography.
One hundred radionuclide angiocardiographies were done in 53 patients with malignancies who were treated with one of the follwing anthracyclines, adriamycin (ADM), daunomycin (DM), aclacynomycin A (ACM), 4'-O-tetrahydropranyladriamycin (THP-ADM).
In patients getting either ADM or DM, there was significant correlation between the changes of 3 parameters (LVEF, PER and PFR) and the cumulative dose each drug, which suggested that these parameters seemed to be useful for the early detection of cardiac dysfunction induced by these drugs. And it was estimated that the limiting total dose of ADM and DM was 360∼600 mg/m², and 1,100∼1,300 mg/m², respectively.
In patients getting ACM, there was no significant correlation between the changes of these parameters and the cumulative dose of this drug (maximum dose: 1,552 mg/m²), which suggested that the cardiotoxic effect of ACM was quite low.
Among 3 parameters, only LVEF was correlated significantly with the cumulative dose in patients getting THP-ADM. It was estimated that the limiting total dose of THP-ADM was 900 mg/m², which suggested that THP-ADM had apparently lower cardiotoxic effect than ADM.

View full abstract

Clinical courses of 13 patients who survived more than 2 years after allogeneic bone marrow transplantation (BMT) were analyzed. Ten patients with acute leukemia were conditioned with cyclophosphamide (CY) and total body irradiation (TBI). Eight of them received marrow graft at the first complete remission stage, and the other 2 received it at the second remission stage. Three patients with severe aplastic anemia were conditioned with CY alone. All except one who was given cyclosporin-A (CsA) were given MTX for prophylaxis of GVHD. Acute GVHD developed in 9 patients, but only 2 patients had severe GVHD (grade II or higher). Chronic GVHD which involved chiefly skin, liver and oral mucosa, developed in 11 patients. Four patients had interstitial pneumonia (IP), but all recovered. Most of patients had viral and/or bacterial infections during one year after BMT, but raly developed such infections after 2 years posttransplant. Serum IgM levels were depressed for 1 year and IgA levels for 2 years posttransplant.

View full abstract

A patient with chronic myeloid leukemia in blast crisis accompanied with severe hypophosphatemia was reported. Hypophosphatemia showed a direct relationship with an increase of tumor cells.
The patient was a 52-year-old man with Ph¹-positive chronic myeloid leukemia. On admission the WBC count was 101,400/μl with 6% of blasts, serum phosphorus and calcium levels were normal. After chemotherapy the WBC count decreased to lower than 10,000/μl. 11 days after discontinuation of the chemotherapy, a rise in number of the WBC was observed. Within a few days the WBC count increased to more than 200,000/μl with 40∼70% of blasts. The serum phosphorus level fell to 0.2 mg/dl and urinary excretion of phosphorus was 9∼12 mg/day. Serum calcium level was normal. Severe hypophosphatemia was not corrected by intravenous administration of phosphate, but serum concentration and urinary excretion of phosphorus increased following chemotherapy. On the fifth day of chemotherapy the patient died because of progressive respiratory failure. At autopsy leukemic cells diffusely infiltrated in bone marrow, liver, spleen and other main organs.
It was suggested that marked hypophosphatemia observed in this case may be caused by a shift of extracellular phosphorus into rapidly proliferating tumor cells.

View full abstract

A Case of 48-year-old female with multicentric angiofollicular lymphnode hyperplasia (MAFH) of the plasma cell type has been reported. She had systemic manifestations such as fever, fatigue, edema, effusion, multicentric lymphadenopathy, hepatosplenomegaly, anemia, thrombocytopenia, hypergammaglobulinemia and elevation of Epstein-Barr (EB) virus related antibody. Biopsy of an axillar lymphnode showed AFH of the plasma cell type. Clinical abnormalities showed an excellent response to vincristine-prednisolone (VP) combination chemotherapy. Although the etiology is unknown, the present case was presumed to be infectious or inflammatory in nature, possibly EB virus. The VP therapy is worth trying for MAFH with systemic manifestations.

View full abstract

A 44-year-old man was diagnosed as having polycythemia vera in 1973 and was treated with vercyte, and subsequently with dibromannitol (DBM). He was in good control during the following 10 years. However, pancytopenia and enlargement of the spleen appeared in August, 1983. This tendency developed during the 10 month period following discontinuation of DBM. Shortly before the patient died from pneumonia in July, 1984, laboratory studies revealed a leukocyte count of 1,300/μl with 20% blast cells in the peripheral blood. At autopsy, myeloblastic infiltration was seen in the bone marrow, spleen and kidneys.
It is assumed that the patient died in transition from the polycythemic stage of this disease to leukemia, and development of pancytopenia reflected abnormal proliferation of blast cells in hematopoietic organs.

View full abstract

Three cases of factitious anemia were reported. Case 1 was a 42 year-old housewife, who was admitted to our hospital because of recurrent severe anemia. During hospital days rapidly progressive anemia recurred periodically. Extensive examination for anemia were performed in vain. She was observed closely and finally found out producing the profuse vaginal bleeding by lacerating with a razor. She was also a typical example of hospital addiction. Case 2 was a 26 year-old male who had been in remission of AML for about 4 years. He was admitted to this hospital with a complaint of paraplegia. During admission severe anemia developed abruptly without an increase of blast cells in bone marrow. Red cells were transfused repeatedly but anemia of unknown cause recurred several times. Accurate diagnosis was made by finding him drawing blood from his antecubital vein. Case 3 was a 26 year-old married female engaged in medicine, who had a past history of anorexia nervosa and drug abuse. She repeated hospitalizations because of iron deficiency anemia of unknown cause. In fourth admission, a number of needles, syrynges and tourniquets were found by examination of her personal possessions.
When factitious anemia is suspected, precise observation of patients by TV monitoring system might be a useful diagnostic procedure.

View full abstract

A 26-year-old female patient with acute lymphoblastic leukemia (ALL) (CALLA⁺, TdT⁺, Ia⁺) in the first relapse received an allogeneic bone marrow graft from an HLA identical sister. Engraftment was demonstrated by the blood typing on 35th day after marrow infusion. Five days later, bone marrow aspirate showed marked increase in CALLA positive blastoid cells (approximately 30%). These cells, however, were negative for TdT and were noticed for next 40 days. Thereafter she had a complete remission for 20 months without further chemotherapy. This case suggests that the appearance of CALLA positive blastoid cells in the bone marrow shortly after bone marrow transplantation may play an important role in the recovery of hemopoiesis in bone marrow recipients.

View full abstract

A case of hairy cell leukemia (HCL) with 14q+ chromosomal abnormality was reported. A 62-year-old man with leukocytosis with splenomegaly showed the presence of hairy cells in peripheral blood. The neoplastic cells showed hairy appearance under phase contrast microscopy. Acid phosphatase activity was positive with diffuse appearance and α-tartrate resistant acid phosphatase activity was also observed. Peroxidase and α-naphtyl butylate esterase activity and phagocytic activities for carbon black and sensitized erythrocytes were not found in these cells. Ribosome lamella complex was negative by electron microscopy. Immunological analysis of neoplastic cells showed FcγR+, SIg+, OKIal+, B₁+ but negative for T cell markers. High resolution G banding analysis showed the translocation between chromosomes 14 and 22 with breakpoints at bands p32.3 and q11.2 and a interstitial deletion of chromosome 1.
This is the first reported case of B-cell HCL revealed chromosomal abnormalites of 14q+ and Philadelphia chromosome like marker. We discuss these findings in related with cellular origin and disease entitiy of HCL.

View full abstract

A 31-year-old man was admitted to our hospital in January, 1985, because of high fever. Hematological examination revealed hemoglobin of 6.5 g/dl, platelet count of 2.1×10⁴/μl and leukocyte count of 3,400/μl with 55.0% blasts, 0.5% neutrophils and 44.5% lymphocytes. Twenty five percent of the blast cells were small, with scanty cytoplasm and prominent nucleolus, while the rest (30.0%) were large, having abundunt cytoplasm with azur granules and Auer body (Auer body-positive cells: 6.5%). A bone marrow aspirate was hypercellular, with 81.2% blast cells consisted of 37.2% small blast cells and 44.0% large blast cells (Auer body positive cells: 13.6%). Thirty percent of blast cells in the bone marrow were positive for myeloperoxidase. Cytogenetic analysis revealed a normal karyotype. The surface marker of mononuclear cells identified by mouse monoclonal antibodies were OKIa1⁺ 51.9%, MY9⁺ 15.9%, Leu12⁺ 49.3%, B4⁺ 17.7% in peripheral blood, and OKIa1⁺ 74.9%, MY9⁺ 35.2%, Leu12⁺ 43.3%, B4⁺ 23.4% in bone marrow. These findings indicated that blast cells of the present case were composed of the two distinct populations of myeloid and lymphoid blast cells. The electronmicroscopic findings of the blast cells also suggested the existence of two population. Acute leukemia has been cosidered to be characterized by the proliferation of committed lymphoid or myeloid stem cells, but the existence of acute mixed leukemia suggested that some cases of acute leukemia were caused by leukemic transformation occurring in the uncommitted multipotential progenitor cells of both lymphoid and myeloid cells as observed in chronic myelocytic leukemia.

View full abstract

A 55-year-old male noticed forceless urination and pollakisuria in summer of 1984. He visited the urological department of Kagawa Medical School in Sep. '85, because his symptoms were getting worse. Urological examinations revealed signs compatible with “benign prostatic hypertrophy” and a transurethral resection of the prostate was performed. The histological examination of the resected specimen revealed “malignant lymphoma, diffuse, small cell type”. His clinical stage was IIB prostate (+) according to the Ann Arbor classification. He was referred to our medical department for systemic chemotherapy. The combination chemotherapy with COPP (cyclophosphamide, vincristine, procarbazine and prednisolone) was started immediately, followed by five courses with no evidence of recurrence.
The occurrence of primary lymphoma of the prostate is rare, less than 1% of prostatic malignancies. Eight cases have been previously reported in Japan, but most of them were found at the far advanced stage with poor prognosis. This is the ninth case, fortunately found at a very early stage.

View full abstract