Recently, incidence of severe infection in leukemia has increased since the combination therapy of multiple antileukemic agents was introduced. These antileukemic agents have side-effect of bone marrow suppression which causes severe neutropenia. The relationship among median leukocyte count during febrile episode (>38°C), duration of leukopenia (<100/mm³) and prognosis and also the relationship between monocyte count and prognosis of infection were studied. A high mortality rate was observed despite relative large dose of antibiotics in case the median neutrophil count during febrile episode was below 100/mm³ and the duration of leukopenia (<100/mm³) prolonged over 8 days. When sepsis had occurred, median neutrophil conut during febrile episode seemed to be necessary more than 500/mm³ to cure the sepsis. The patients who died of sepsis rarely developed increment of monocyte count over 100/mm³ after onset of febrile episode. Since transient severe neutropenia in leukemia has become very frequent with modern therapy and we have never had specific drugs to kill only leukemic cells yet, other procedures to prevent infection, such as germ free isolator and/or leukocyte transfusion should be applied in addition to antibiotics as supportive care.

View full abstract

Determination of Total Iron Binding Capacity (TIBC) using Res-O-Mat Fe kit [TIBC] offered by Daiichi Radioisotope Laboratories, Ltd. was investigated. This kit method is to determine the total iron binding capacity of transferrin by counting the radioactivity of ⁵⁹Fe which was bound to transferrin after removing the serum iron from the transferrin by adding 0.6% citric acid. About 95% of unbounded ⁵⁹Fe was adsorbed by Resin Strip (Amberlite IRA 400) after 90 minutes incubation, and this method is very simple and sufficient for clinical use. TIBC value determined by this method well agreed with the value of (UIBC+SI) determined by the other method. Denaturation of transferrin due to change of serum pH was investigated by Ouchterlony's method and immunoelectrophoresis, but no change of transferrin was observed. Tf value determined by immunodiffusion method showed fairly good correlation with TIBC value. SI value determined by colorimetry also well agreed with the value of (TIBC-UIBC). This kit method is found to be simple and useful in clinical application.

View full abstract

Neocarzinostatin was administered to 23 cases of acute leukemia for remission induction and to one case for consolidation treatment. It was given by intravenous drip infusion in a dosis of 0.04 mg/kg daily for 4-10 days. Complete remissions were induced in 3 cases, and imcomplete remissions were induced in 7 cases.
By the analysis of decrease curve of leukemic cells in blood after NCS administration, it was estimated that the initial rate of decrease is high, the rate of deceleration is high and the duration of decrease is short, compared with other antileukemic drugs, such as cytosin arabinoside and 6 MP. It was also shown that the rate of decrease of leukemic cells in the bone marrow is low and the rate of decrease of neutrophile leukocytes in blood is also low. By such findings NCS seems to belong to a group of antileukemic drugs such as daunomycin or 1-asparaginase from the mode of decrease curve of leukemic cells.
Side effects such as nausea, fever and skin rush were observed, although the intradermal tests had been negative in all cases.
Neocarzinostatin is considered to be useful in the treatment of acute leukemia.

View full abstract

The behavior of sideroblasts following cancer chemotherapy was studied for the evaluation of erythropoiesis. Fifty-nine patients with malignant neoplasms were employed for this research. Several regimens of chemotherapy were carried out for 51 times. Before and after each medication, changes of the type in sideroblastogram were examined. Before medication, 33 iron deficiency type cases and 18 normal type cases were observed in sideroblastogram. In comparison between before- and after- medication, following results were obtained: 23 cases shifted to the right, 27 cases showed no change and one case shifted to the left in the graph.
Next, we divided these cases into two groups, i.e., a group shifted to the right (SG) and an unchanged group (UG). Hematologic depression was studied compairing SG with UG and the results were as follows: erythrocyte depression (SG:7 cases, UG:none), decrease of hemoglobin (SG:4, UG:none), leukopenia (SG:5, UG:none), thrombocytopenia (SG:3, UG:none), NCC depression (SG:7, UG:1), increase in E/M ratio (SG:4, UG:1) and increase in serum Fe (SG:6, UG:none).
These results showed that not only the cases with erythropoietic disturbances but also almost all the cases with other myelo-suppression belonged to the SG. In iron metabolism, sideroblasts were found during the dynamic phase of hemoglobin synthesis from non-hemin iron to hemin iron in erythroblasts. Based on these findings, it was concluded that the appearance of sideroblasts should give an useful information regarding the hematopoietic disturbances following cancer chemotherapy.

View full abstract

A 39-year-old male patient with severe anemia, jaundice and episodes of hemoglobinuria was diagnosed to have PNH, because of positive Ham and sucrose hemolysis tests, and decreased erythrocyte acetylcholinesterase activity in addition to the usual findings found in hemolytic anemia. The patient showed complex clinical manifestations of the disease and serum hepatitis. Elevated serum GOT and LDH persisted constantly in the whole course of the disease.
He frequently developed hemolytic crisis followed by hemoglobinuria after the intravenous as well as peroral iron administration for the treatment of iron deficiency anemia. The hemolytic crisis has been, however, markedly supressed when iron is administered in combination with a small dosis of steroid hormone. Vitamin E was also found to be effective for the improvement of the laboratory findings.
He died suddenly of hemolytic crisis, complicated by bronchopneumonia and uremia.

View full abstract

A 24-year-old man was diagnosed as hyperthyroidism and had been given mercazole 30 mgm. daily since January 1973. At the end of March 1973 pancytopenia was noticed in his peripheral blood, and he was referred to the Department of Hematology, Toranomon Hospital and admitted on March 30, 1973.
On admission hemoglobin was 7.0 Gm/100 ml, RBC 2,730,000 per cu. mm., hematocrit 22%, reticulocytes 0.8%, WBC 1,900 per cu. mm. with 4.5% myeloblasts with occasional Auer bodies and platelets 21,000 per cu. mm. The sternal marrow aspirate showed a hypercellular material with 63.0% atypical myeloblasts. Diagnosis of acute myeloblastic leukemia was made.
Blood group examination on admission revealed a weakly positive agglutination of the patinet's red cells against anti-A and negative against anti-A₁ serum. In the reverse serum grouping, the patient's serum agglutinated only red cells of group B and no agglutination occurred against the red cells of groups A, O, and A₁. A few years ago he was known to be of group A on a test at the blood bank. His father was of group O and mother of group A₁.
After an intensive therapy a complete remission was obtained on June 16, 1973, when his blood group was diagnosed to be A₁; this condition remained unchanged until May 1974.

View full abstract

The patient, a 71-year-old male, with erythroleukemia and multiple early cancers of the stomach was reported.
He visited his home doctor because of epigastralgia and was made a diagnosis of gastric cancer. Then he was referred to our hospital to receive an operation of gastric cancer. The peripheral blood findings on admission revealed anemia (RBC 1,610,000/mm³), leukocytosis (WBC 17,000/mm³, Blast 29%), and thrombocytopenia (40,000/mm³). Bone marrow examination revealed erythroid hyperplasia with megaloblastoid cell (3.2%) and PAS positive erythroblast (7%), and myelogenous leukemic change (atypical myeloblast 14.6%). The vitamin B₁₂ level was normal. A polypoid cancer of pyloric antrum and an ulcerated cancer of gastric angle were found by gastroendoscopy and both biopsy-specimens showed adenocarcinoma tubulare. A diagnosis of erythroleukemia and of multiple early cancers of the stomach was made and a large amount of fresh blood, predonine (30 mg/day, per os) and 6MP (100 mg/day, per os) were administerted. After one month, his hematological findings were transformed to acute myelogenous leukemia. He was died, six months later.
The chief autopsy findings were as follows:
1) Myelogenous leukemic bone marrow.
2) Two gastric cancers, reaching to submucosa.
No metastasis was found in regional lymph nodes and the other organs.

View full abstract

Running infusion of Cyclocytidine (CC) (2, 2'-anhydro-1-β-D-arabinofuranosylcytosine hydrochloride) was performed in 25 patients of acute leukemia (20 cases of acute myelogenous leukemia, 3 of acute erythroleukemia and 2 of blastic crisis of chronic myelogenous leukemia).
The chemotherapeutic schedules were as follows
Regimen I: CC 10 mg/kg i.v. and prednisolone 30 mg p.o. daily.
Regimen II: CC 10 mg/kg i.v., 6-MP 100mg p.o. and prednisolone 30 mg daily.
Regimen III: 3-day courses of CC 10∼20 mg/kg and daunorubicin 20 mg at weekly intervals. 6-MP and prednisolone were administered as Regimen II.
Regimen IV: Vincristine 2mg, and CC 20 mg/kg for 3 consective days at weekly intervals. 6-MP and prednisolone were administered as Regimen II.
One patient with AML attained complete remission by Regimen I. The same results were obtained in 30% by Regimen II, 50% by Regimen III and 75% by Regimen IV. Of 14 AML patients who had received no prior treatment, 9 attained complete remission and 1 attained partial remission.
Pain of parotid glands was one of the most frequent side effects in the patients treated with 20 mg/kg of CC. Gastrointestinal disturbances were less than those by cytosine arabinoside. In 3 patients vertigo and orthostatic hypotension were observed.
The median survival from the time of onset in 20 AML patients treated with CC was 9 months or more.

View full abstract

A case of Sjögren's syndrome associated with macroglobulinemia is prsesnted. The patient, 28-year-old female, was admitted to our clinic because of dry eyes and mouth, and salivary gland enlargement in September, 1973. The sicca symptoms, especcially dryness of eyes, purpura in lower extremities and polyarthralgia had developed 5 years prior to the admission. Swelling of eyelids and salivary glands had occurred 3 months before admission and she had undergone splenectomy with the diagnosis of hypersplenism in a local hospital 2 months before admission to our clinic. The diagnosis of Sjögren's syndrome was made based on these clinical symptoms and on the histologic findings of biopsied salivary gland showing dense infiltrate of small lymphocytes, concentrated in ductal areas and around venules, associated with atrophy of acinar tissue.
The presence of monoclonal macroglobulinemia with κ and λ type light chains was demonstrated by immunoelectrophoresis, and the values of IgM ranged from 700 to 850 mg/100 ml. The sedimentation constant of the the macroglobulin was 26S and 18S, and the viscosity of serum was greatly increased. Enlargement of salivary glands and lymph nodes including both pulmonary hilar nodes increased progressively. In addition, hepatic enlargement up to 6 finger breadths below right costal margin and pleural effusion caused dyspnea and general fatigue. The patient responded excellently to chlorambucil with the disappearance of sicca symptoms and lymphadenopathy and decrease of hepatomegaly.
The relationship between Sjögren's syndrome and macroglobulinemia as well as malignant lymphoma was discussed.

View full abstract