Fifty-seven patients in initial phase of acute promyelocytic leukemia (APL) were treated in the same department with heparin infusion, platelet transfusions, and two related induction regimens both including cytosine arabinoside and daunorubicin. Clinical and biological findings at presentation were studied. The complete remission (CR) rate was 53%. Twenty-seven patients (47%) died during the initial course of the disease, either before day 5 (early death [ED], n = 7) or after day 5 (death in aplasia [DA], n = 20). Most ED was due to intracerebral hemorrhage (6/7), especially when large hemorrhages had been seen on fundus oculi examination. Most DA was due to multivisceral failure (9/20). No correlation was found between initial disseminated intravascular coagulation (DIC) and death. However, the worsening of coagulation parameters during induction therapy, with or without initial DIC, significantly increased the occurrence of renal and respiratory failure which were particularly frequent during the first month. The median duration of survival was short (3.5 months) and the median duration of CR (11 months) was similar to that of other acute myeloid leukemias treated with the same regimens. The possible causes of the high mortality observed during the initial courses of APL and the possible benefit of a more graduate induction chemotherapy are discussed.

Acute promyelocytic leukemia in 57 previously untreated patients.

Publisher Summary Surfaces of lymphocytes and macrophages in large part determine and control the multiplicity of cellular interactions that characterize immune function. The organization and physiology of cell surfaces are in turn determined by intrinsic plasma membrane markers and receptors and by the state of the underlying cell cortex, which contains the cytoskeleton and cytomusculature. This critical interrelationship between cell cortex and plasma membrane and its role in determining immunologic function are discussed in this chapter. Two general kinds of plasma membrane interactions are considered in detail. The first is an active process of motion and/or recognition initiated in the cortex and usually involving formation of uropode and microvilli where receptors are concentrated. The second is passive recognition in which resting lymphocytes are exposed to ligands that bind to and cluster receptors, thereby perturbing the cells' plasma membranes and initiating the biochemical events of activation. All factors that could interfere in one or another way with membrane organization could modulate cell activation but the most remarkable one is the stringent requirement for clustering shown by lectins and antibodies.

Plasma membrane and cell cortex interactions in lymphocyte functions.

Seven adults with acute promyelocytic leukemia (APL) and disseminated intravascular coagulation were treated for remission induction with daunorubicin hydrochloride and prednisone. In all patients the coagulopathy was managed with continuous-infusion heparin sodium and vigorous transfusion with platelets, cryoprecipitate, and fresh frozen plasma. Five patients survived induction; they all achieved complete remission (CR). Median duration of CR was 27+ months; two patients presently survive in their initial CR at 28 and 48 months. Recognition of APL as a distinct type of acute leukemia and prompt initiation of treatment aimed at rapid cytoreduction and control of the coagulopathy has resulted in a prolonged disease-free survival for the majority of patients. ( Arch Internal Med 138:1677-1680, 1978)

Acute promyelocytic leukemia. Management of the coagulopathy during daunorubicin-prednisone remission induction.

Since 1961, when Part A of this Handbook appeared, experimental lymphocyte research and immunology have provided so many revolutionary data that it is necessary to reassess our cytologic and histologic bases of classification. Therefore, some of the most important data will be presented here. This will lead to a substantial widening of our horizons of 1961 and also to certain corrections. These cannot affect the morphology itself, of course, but rather its interpretation, in particular that of the cytogenetic derivation of the cells and their different morphologic appearances. Above all, it has become evident that lymphocytes and plasma cells are not derived from reticulum cells. Instead, stimulation and transformation of small lymphocytes result in the development of large blast cells (immunoblasts, centroblasts), which serve as the precursors of lymphocytes and plasma cells. Some other variants (stimulated lymphocytes, “immature sinus histiocytes”) that have been separated morphologically are probably such transformed or activated lymphocytes. Furthermore, it has been shown that most macrophages and one of their specific functional forms, namely, epithelioid cells, are of monocytic origin.

The Cytologic, Histologic, and Functional Bases for a Modern Classification of Lymphomas

The great selectivity of binding of antibody molecules combined with the almost limitless range of their specificities make them ideal “natural” reagents for the identification and visualization of cellular constituents. The use of antibodies as tracers for light microscopy was introduced by Coons and his collaborators (Coons et al., 1941; Coons and Kaplan, 1950), who succeeded in preparing fluorescent tracers by coupling covalently antibodies to suitable organic chemical groups capable of emitting fluorescent light (fluorochromes). Subsequent improvements in the coupling methods and in instrumentation have contributed to making immunofluorescence a simple and reliable technique which is now used routinely in many laboratories. The extension of this technique to the electron microscopic level required the introduction of markers of sufficient contrast to be detected against the background of the surrounding material. This was achieved by Singer and his coworkers (Singer, 1959; Singer and Schick, 1961), who used ferritin as a marker and developed a method to bind it covalently to an antibody. Ferritin is a unique marker for electron microscopy, as its electron-dense iron-containing core can be visualized and recognized even at relatively low magnification. Subsequently, several other markers (see Section 3.2) were introduced into electron microscopy, notably enzymes such as peroxidases which are capable of giving an electron-dense reaction product easily recognizable in sections (Nakane and Pierce, 1966; Sri Ram et al, 1966; Avrameas, 1969). Ferritin, however, still remains the most widely used marker for electron microscopy, especially for membrane studies.

Immunoelectron Microscopy and Immunofluorescence in Membrane Biology

Surface immunoglobulins (sIg) were detected on human lymphocytes by immunoelectron microscopy with peroxidase-conjugated antibodies. Blood, marrow, and thymus cells from normal individuals and patients with lymphoproliferative disorders were examined. Samples were fixed before exposure to specific reagents. Normal lymphocyts with detectable sIg, i.e. B lymphocytes, were characterized by a villous surface; nonlabeled blood lymphocytes and thymocytes were smooth cells. Intermediate cells were also found which in sections appeared moderately villous and labeled, thus identified as B lymphocytes. Further evidence for a relationship between villous surface and sIg was given by the finding of a few lymphocytes with polar concentration of labeled microvilli. In chronic lymphocytic leukemia patients, most cells exhibited a villous surface with parallel variations of the number of microvilli and of anti-immunoglobulin-binding capacity. However, some labeled smooth blastic cells were also observed. On the other hand, abnormal lymphocytes from Sezary's syndrome which could exhibit segments of villous membrane had no detectable sIg. This study confirms that in most cases human B lymphocytes have a characteristic surface appearance and that the detection of sIg in normal lymphocytes correlates with the presence of microvilli.

/pdf/the-surface-morphology-of-human-b-lymphocytes-as-revealed-by-4apou3frj9.pdf

The surface morphology of human B lymphocytes as revealed by immunoelectron microscopy.

Emergency treatment of acute promyelocytic leukemia and its hemorrhagic complications. Apropos of 30 cases

Peroxidase conjugated antibodies were applied to cell suspensions in order to detect surface associated immunoglobulins. Cell suspensions were fixed prior to incubation with reagents, a procedure avoiding membrane alterations induced by antibodies to surface component. By immunoelectron microscopy an identification of B lymphocytes could be made with simultaneous observation of their surface architecture.

/pdf/surface-features-of-cells-in-human-lymphoproliferative-16pleruyvm.pdf

Surface features of cells in human lymphoproliferative disorders. An immunoelectron microscopy study.

A and A1 antigens have been detected on cells of the human erythrocyte series by immunoelectron microscopy. These antigens have been revealed by an indirect method involving various anti-A and anti-A1 antibodies (allo, auto, hetero-antibodies) and peroxidase-conjugated anti-immunoglobulin antibodies. Immunologic labelling has been carried out with erythrocyte or bone marrow cell suspensions which were fixed prior to incubation with reagents. Cells from various A phenotypes were examined. A and A1 antigens were visualized on maturing normoblasts, at every developmental stage. In addition cell to cell variations of the surface labelling of erythrocytes was found in normal phenotypes, suggesting the existence of several populations of cells according to antigenic load.

L'hétérogénéité de la distribution cellulaire des antigènes A érythrocytaires Etude au microscope électronique

Application of the immunoperoxidase method to the study of the membrane of human lymphocytes

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