Mitsuhiro Omine

Prognostic aspects of aplastic anemia in pregnancy

ZusammenfassungBerichte über Schwangerschaften bei aplastischer Anämie oder das Auftreten einer aplastischen Anämie in der Schwangerschaft sind selten. Anhand von 6 eigenen derartigen Fällen und von 43 Fällen aus der Literatur wurden die hämatologischen und klinischen Befunde in Hinsicht auf ihre prognostische Bedeutung untersucht.Bei den hämatologischen Parametern war lediglich die Hämoglobinkonzentration von prognostischer Bedeutung. Bei Auftreten der aplastischen Anämie vor der Schwangerschaft war die Prognose besser als bei Auftreten während der Schwangerschaft. Der Prozentsatz der erfolgreich ausgetragenen Schwangerschaften stieg von 21% vor 1958 auf 67% in der Zeit von 1959 bis 1969 und auf 71% nach 1970. Blutungen und Infektionen waren die beiden wichtigsten mütterlichen Todesursachen. Aus den Ergebnissen ist abzuleiten, daß bei ausgeprägtem Kinderwunsch und gutem Allgemeinzustand von einer Schwangerschaft bei bestehender aplastischer Anämie nicht immer abgeraten werden muß und daß andererseits bei einer progredienten aplastischen Anämie, die in der Schwangerschaft auftritt, möglichst früh eine Schwangerschafts-unterbrechung erfolgen muß.SummaryOur recent experience on six cases of aplastic anemia complicated with pregnancy is described. In addition, 43 similar cases were collected from the literature and reviewed to analyze some prognostic aspects of this relatively rare but potentially serious complication. Clinical and hematological data were treated to extract some clinically meaningful factors in relation to the success and failure of pregnancy.Among initial hematological parameters, no significant difference was found between successful and unsuccessful cases with an exception of hemoglobin concentration. The patients diagnosed as aplastic anemia prior to conception demonstrated an better outcome of pregnancy as well as survival rate of mother when compared with those diagnosed during pregnancy. Mortality has apparently improved after the late 1950s. Success rate of pregnancy before 1958 was 21% while it was 67% and 71% in the era of 1959–1969 and after 1970, respectively. However, hemorrhage and infection remained to be two major causes of maternal death in both eras.Based on these observations, the currently recommendable attitude to this complication is discussed.

A long term follow-up of a randomized trial comparing interferon-α with busulfan for chronic myelogenous leukemia

Abstract To evaluate the long-term effectiveness of interferon- α (IFN- α ) therapy in patients with chronic myelogenous leukemia (CML) in chronic phase, we examined the updated outcomes of 159 patients who had been enrolled between 1988 and 1991 into a randomized trial comparing IFN- α with busulfan. At a median follow-up of 73 months, the median survival was 71 months in the IFN- α group and 55 months in the busulfan group ( P =0.0563), and the median time of remaining in chronic phase was 58 months in the IFN- α group and 39 months in the busulfan group ( P =0.4676). Landmark analysis showed a significant advantage in survival ( P =0.009) and duration of chronic phase ( P =0.0001) in patients with any cytogenetic response among the IFN- α group. About half patients were discontinued IFN- α administration in spite of cytogenetic response in this study. It appears that continuation of IFN- α might possibly confer a survival advantage. Pretreatment factors associated with cytogenetic response included high hemoglobin level, low percentage of peripheral basophils and low leukocyte counts. Multivariate analysis identified lower percentage of bone marrow basophilia ( P =0.007) for survival advantage. If a group with a very good prognosis is predicted by a new prognostic model, it might be an option to wait for bone marrow transplantation.

Proliferative kinetics of the leukemic cells in meningeal leukemia.

The proliferative kinetics of leukemic cells was investigated in the cerebrospinal fluid (CSF) and the leptomeninges of 5 patients with meningeal leukemia (ML) and 15 selected autopsies showing meningeal involvement. The 3H‐thymidine labeling index (TLI), mitotic index (MI) and 3H‐uridine labeling index (ULI) of leukemic cells in the CSF at the time of diagnosis were 0.7 ± 0.2, less than 0.01 and 96.2 ± 0.7%, respectively. The TLI was found to be higher at the time of recurrence than at the initial diagnosis of meningeal leukemia. The grade of leukemic cell infiltration was classified according to Prices criteria. The mitotic index was also estimated on the histologic sections. An infiltration of Grade 2 or greater was observed in all 4 patients who had not received an intrathecal administration of methotrexate (MTX). The clinical course of 2 patients with a higher MI (0.88 and 0.32%) was shorter than the other 2 (0.03 and 0.01%). In the patients who did not show clinical manifestations of ML, the infiltration of leukemic cells in the leptomeninges was mild in degree, and the MI was less than 0.01%. Likewise, mild infiltration and low MI was observed in 8 cases treated with an intrathecal administration of methotrexate. These findings seem to support the general concept that the proliferation of leukemia cells infiltrating leptomeninges is remarkably slow at an incipient stage of ML; then it undergoes a gradual acceleration, possibly slowing down again at an advanced stage of the disease.

Clinical features of common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma: report of four cases.

SummaryFour patients with common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma are presented. The subclasses of monoclonal protein were IgDκ (1 case), IgAλ (1 case), and IgAκ (2 cases). Bence Jones proteinuria was seen in all cases. The clinical stages were determined as IIA (2 cases) and IIIA (2 cases). All patients died with a median survival time after diagnosis of 62 days due to rapid development of renal failure (3 cases), and renal insufficiency and pneumonia (1 case). According to light microscopic evaluation, these myelomas corresponded to plasmablastic (1 case), immature (2 cases), and intermediate (1 case) types. Both CALLA and a cytoplasmic immunoglobulin identical with the serum monoclonal protein were simultaneously detected in single cells from all cases using immunofluorescent double labeling. These findings suggest that CALLA-positive and plasmablastic myelomas constitute clinically a subgroup characterized by extremely poor survival but they represent cytologically different subcategories.

Congenital dyserythropoietic anemia type I: report of a pair of siblings in Japan.

ZusammenfassungBisherige Mitteilungen über Patienten mit kongenitaler dyserythropoetischer Anämie betreffen ausnahmslos Individuen kaukasischer Rasse. In der vorliegenden Arbeit wird erstmals über ein japanisches Geschwisterpaar berichtet, das die typischen lichtmikroskopischen, elektronenmikroskopischen und funktionalen Veränderungen dieser seltenen hereditären Erkrankung aufwiesen. Die Tatsache, daß die Eltern blutsverwandt waren, stützt die Annahme eines autosomal-recessiven Erbgangs.SummaryThis is the first case of two siblings with congenital dyserythropoietic anemia (CDA) type I to be reported from a Japanese family. Both of these cases showed characteristic morphological aberrations of erythroid precursors, ineffective erythropoiesis, and negative acidified serum test. The ultrastructural study of erythroblasts also revealed characteristics quite compatible with CDA type I.

Ki-1-Positive Large-Cell Anaplastic Lymphoma with Protean Manifestations Including Central Nervous System Involvement

A 26-year-old female with Ki-1-positive large-cell anaplastic lymphoma is reported. The neoplastic cells were phenotypically and genotypically of T cell origin. Initially, neoplastic cells invaded the skin and lymph nodes, and then invaded the sternal and vertebral bones, ribs and the iliopsoas muscle. Central nervous system (CNS) involvement with paraplegia, large tumor mass formation in her breast and pleural infiltration ensued in succession. This case illustrates the protean manifestations of Ki-1-positive large cell anaplastic lymphoma complicated with CNS involvement.

Possible causal association between ulcerative colitis and idiopathic thrombocytopenic purpura

SummaryA 24-year-old Japanese male having ulcerative colitis and idiopathic thrombocytopenic purpura is described. When the symptoms of ulcerative colitis were manifest during his clinical course, the platelet life-span was shortened and the platelet associated IgG level was increased. Thus, causal association between the two diseases may be suggested.

A Case of Juvenile Erythroleukemia with Uncoordinated Expression of Fetal Red Cell Markers

A 7-year-old boy with juvenile erythroleukemia is described, whose red cells demonstrated a high content of Hb F with fetal structure and yet contained carbonic anhydrase at adult red cell level. The findings seem to exemplify the occurrence of uncoordinated expression of fetal markers and consequently the incomplete reversion to fetal-type erythropoiesis in a hematologic malignancy.

A monoclonal antibody with reaction spectrum covering acute leukemia and T-lineage cells.

A mouse monoclonal antibody (MA-10) was raised using cells of a patient with AML (M2). MA-10 reacted with leukemic cells in 44 out of 60 AML cases. Intense reaction was observed especially in 32/38 cases with M1 and M2, as well as 9/9 with common ALL and 2/2 with T-ALL. No appreciable reaction was observed with mature blood cells with only exception of T cells. In-vitro addition of MA-10 did not affect the growth of GM-CFC and BFU-e from two patients with CML in chronic phase. MA-10 identified three polypeptides of approximate mol. wt of 74,000, 50,000 and 30,000.

Altered DNA sedimentation by the presence of erythrocytes in alkaline sucrose gradient centrifugation.

Abstract The presence of a relatively small number of red cells was found to affect DNA sedimentation profile of normal lymphocytes and acute leukemia cells, as observed by the alkaline sucrose gradient centrifugation technique coupled with the fluorometric measurement of DNA. Significant alteration was observed at a nucleated cell/erythrocyte ratio of 20 1 to 0.2 1 , resulting in retardation of the S 1 2 value and the entire sedimentation profile. This effect seemed to be rather specific to erythrocyte lysate, since corresponding amounts of erythrocyte ghost, IgM, bovine serum albumin, and an increased number of nucleated cells did not influence the profile to an appreciable degree.