Eiji Morioka

Demonstration of three distinct immunological disorders on erythropoiesis in a patient with pure red cell aplasia and autoimmune haemolytic anaemia associated with thymoma

Summary. A patient with pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA), associated with a thymoma which had already been removed, was studied in order to investigate the pathogenesis of PRCA and AIHA. The autoantibody eluted from the surface of the patients red blood cells (RBC) reacted with the large E antigen of the Rh complex. Immunoglobulin‐G (IgG) purified from the patients serum suppressed CFU‐E and BFU‐E but not CFU‐GM colony formation in the presence of complement. This antibody was not adsorbed with large E antigen. T‐lymphocytes in the bone marrow suppressing autologous CFU‐E and BFU‐E colonies were demonstrated. Thus, three distinct immunological disorders on erythropoiesis were present in this patient with PRCA and AIHA associated with thymoma in a thymectomized state.

Acute ‘bilineal‐biphenotypic’ leukaemia

We describe a unique case of hybrid leukaemia with bilineal and biphenotypic features. The coexistence of lymphoblasts and monoblasts was determined morphologically and cytochemically. Immunofluorescence and immunohistochemical analysis revealed that each blast population had both T lymphoid (CD2, cytoplasmic CD3) and myeloid (CD11, CD13, CD15) markers. Southern blot analysis of DNA extracted from the lymph node biopsy demonstrated the presence of monoclonal rearrangement of the TcR‐Cβ gene. Cytogenetic analysis of the bone marrow cells showed a karyotype of 48, XY, 7q + in all of the metaphases examined. These observations are suggestive of a monoclonal origin for these two distinct blast populations.

Treatment of four patients with myelodysplastic syndrome with a small dose of aclacinomycin-A☆

The effect of a small dose of aclacinomycin-A (ACR) was examined in two patients with refractory anemia (RA) and two with refractory anemia with excess of blasts in transformation (RAEB-t). ACR (7 or 14 mg/m2) was given for 10 days in a 2-h per day drip infusion. Clinical symptoms and laboratory data improved in 3 of these 4 patients. In a patient with RA, marked increase in reticulocytes and elevation of the hemoglobin level from 6 to 9 g/dl was observed after two courses of ACR therapy. In two with RAEB-t, Auers rod bearing cells disappeared in the bone marrow and megaloblastic change of the erythroblasts was diminished in one patient. Hemoglobin levels rose from 4.7 to 10 g/dl in one, and platelets and WBC increased in another. No effect was seen in a patient with RA. The cytoreductive effect of ACR was minor compared to the therapy with small dose of cytosine arabinoside (Ara-C). Therefore, ACR warrants further consideration for the treatment of patients with MDS.

Clinical characteristics of hybrid leukemia : report of five cases

We studied clinical and biological features of five cases of hybrid leukemia. Three of the five patients were classified as biphenotypic leukemia because of the coexpression of myeloid/B lymphoid markers in patients 1 (FAB M2) and 2 (FAB CMMoL) and myeloid/T lymphoid markers in patient 3 (FAB M4). Patient 4 was identified as bilineal-biphenotypic leukemia because acute myelogenous leukemia (AML) (FAB M4) and acute lymphoblastic leukemia (ALL) (FAB L1) coexisted and each population coexpressed myeloid and T lymphoid markers. Patient 5 was identified as bilineal leukemia due to the conversion from AML (FAB M1) to ALL (FAB L1) at an interval of 3 months. The Philadelphia (Ph1) chromosome was negative in all cases. A leukemic blast colony formation using cell line 5637 conditioned medium as a stimulator was obtained in all four patients examined. Three of the five patients had been suffering from so-called stem cell disorders such as aplastic anemia in patient 2, trilineage myelodysplasia in patient 4 and refractory anemia with excess of blasts in transformation in patient 5. The pre-existing impairment of pluripotent stem cell was probably the background of these hybrid leukemia. Hybrid leukemia appears to have an inferior prognosis: an AML-directed chemotherapy resulted in a low remission rate (2/5) with a short duration of relapse free survival (1/2) and an ALL-directed chemotherapy produced no remission (0/3). Chronological phenotypic analysis revealed that hybrid features of leukemic blasts disappeared at the time of relapse in patient 1 and progression to AML in patient 2. Monitoring of lineage-associated markers should be required for the management of hybrid leukemia.

Lactic acidosis complicating adult T-cell leukemia: report of two cases

To the editor: Lactic acidosis is a complication of severe tissue hypoxia in patients with shock, the so-called lactic acidosis type A. Lactic acidosis occurs spontaneously in patients with severe liver disease, uncontrolled diabetes mellitus, and malignant neoplasm, the so-called lactic acidosis type B (1-3). Lactic acidosis is a serious complication of hematopoietic malignancies; about 50 % die of this complication (4, 5). We report on 2 patients with lactic acidosis associated with relapses of ATL, one with the smouldering and the other with the chronic type of ATL. Patient 1, was a 46-year-old male with smouldering ATL; the WBC increased to 147.5 x 109/1 (ATL cells 93.5%) 9 months after disease onset. He developed cyanosis and Kussmaul-like respirations, and became somnolent. Arterial blood gas analysis revealed metabolic acidosis with a pH of 7.197, PO, 82.5 mmHg, PCO, 15.4mmHg, HCO, 5.8 mEq/l, and 0, SAT 92.6%. The serum level of lactic acid rose markedly to 34.4 mEq/l (normal, less than 2.0 mEq/l) and the anion gap was 37.2 mEq/l (normal, less than 12mEq/l). A total of 120mEq of sodium bicarbonate was administered intravenously. Treatment with mitoxantrone 10 mg, and etoposide 100 mg/m2, was started within 120 hours of the onset of acidosis. Blood gas analysis revealed a pH of 7.489, PO, 92.8 mmHg, PCO, 41.4 mmHg, HCO, 3 1.2 mEq/l and 0, SAT 92.8%. The lactic acid level was near normal at 1.6 mEq/l. The ATL cells decreased to 70%, and the hepatobiliary enzymes (T.Bi1. 2.4-0.5 mg/dl, GOT 1784 13 Ujl, GPT 191-+21 U/l and LDH 5832-365 Ujl) returned to the normal range (Table 1). The LA in this case is thus considered to be type B. Patient 2, a 55-yr-old male, was diagnosed as suffering from the chronic type of ATL complicated by liver cirrhosis (LC). He developed disseminated intravascular coagulation (DIC) 7 months after the onset, exhibiting mucosal bleeding and tarry stools. Gabexate (FOY) 2000 mg/day was administered without improvement in the DIC. He developed a generalized rash typical of ATL. The WBC again rose to 25.5 x 109/1 (ATL cells 54.5%). One week later, he suddenly became dyspneic. Arterial blood gas analysis then showed pH 7.18, PO, 82 mmHg, PCO, 12.4 mmHg, and HCO, 4.4 mEq/l, indicating metabolic acidosis. The lactic acid level was 37.7 mEq/l and the anion gap was 35.6 mEq/l. A total of 160 mEq of sodium bicarbonate was administered intravenously to treat the LA. The administration of etoposide (100 mg/m2) was also begun. While bicarbonate temporarily improved the acidosis, the lactate level again rose rapidly, and the patient died 33 hours later. Autopsy revealed widespread infiltration of ATL cells into various organs with LC and DIC. Thus, the acidosis in this case is considered to be a combination of types A and B lactic acidosis. The LA associated with hemopoietic malignancy is generally attributed to circulatory impairment; an increased production of lactate by the tumors, and/or by an impaired metabolism of hepatic lactate (6). Since the normal liver is able to increase the utilization of lactate via gluconeogenesis and oxidation by up to 10-fold (6), an enhanced production of lactate by the tumor also does not explain the marked lacticacideniia. Gary et al. (4) reported that the infiltration of tumor cells into the liver was observed in 25 cases of malignant lymphoma with LA, and noted that the gluconeogenesis of normal liver cells was decreased in those cases. Concerning the LA without tissue anoxia in a leukemia patient, Field et al. considered that the LA was due to the packing of bone marrow with leukemia cells leading to an insufficient supply of oxygen to the cells followed by anaerobic glycolysis (5). Both our patients showed an increase in leukemic cells and hepatopathy. In addition, Case 2 developed LC and DIC. In Case 1, effective chemotherapy induced a decrease of ATL cells and a normalization of the lactate level. In Case 2, it is suggested that the patient’s circulatory status was impaired by DIC. The presence of LC decreased his rate of lactate utilization, and he died. Alkali therapy is generally administered as symptomatic treatment for LA. However, its utility is questionable in the critically ill. Cooper et al. reported that bicarbonate does not improve the hemodynamics of patients who are critically ill with LA (7). Sodium bicarbonate administration has been re-

Effect of human G-CSF on clonogenic cells in acute myeloblastic leukemia

The effects of purified human native granulocyte colony-stimulating factor (G-CSF) on the growth of clonogenic leukemic blast cells from 10 Japanese patients with acute myeloblastic leukemia (AML) were studied, using an in vitro leukemic blast colony assay. The clonogenic leukemic blast cells from six patients with AML were stimulated to form colonies in viscous medium in vitro by the addition of 100 ng/ml G-CSF. The possibility that G-CSF may be a leukemic blast growth factor warrants further attention.

A case of hereditary spherocytosis complicated with aplastic crisis induced by parvovirus infection

症例は35才の先天性球状赤血球症の女性で,発熱,全身倦怠感にて発症.入院時骨髄で赤芽球の著減と特異な形態異常を認めた.血清中parvovirus抗原を免疫拡散法にて証明したが,その2日後にはseroconversionを起こし,抗体陽性,抗原陰性となった.血清中に,電顕にて約25nmのウイルス粒子を証明した.急性期血清は,患者回復時の骨髄のCFU-Eを抑制した.入院時,血小板,白血球数の減少がみられ,赤芽球系以外の造血系細胞に対する影響も推測された.本邦ではaplastic crisis例でのparvovirusの検出報告はまだ極めてまれで,貴重な1例と考え報告した.