2 cases of acute disseminated intravascular coagulation in normal pregnancy and as the first symptom of acute promyelocytic leukemia

Two cases of the acute disseminated intravascular coagulation (DIC) are presented. DIC in the first case was diagnosed in healthy pregnant woman without any obstetric pathology. This patient recovered completely. The acute DIC in another patient preceded the acute promyelocytic leukemia. The patient died despite a control of DIC. DIC therapy included antifibrinolytic agents and additionally corticoids in pregnant patient. Heparin was not administered because of post partum period and foreseen cytostatic therapy in the leukemic patient.     

Significance of PAS-positive myeloblastic leukemia]

We refer to 48 adult patients suffering from acute myeloblastic leukemia, whose leukemic cells showed a typical cytochemical pattern: i.e. weak staining for peroxydase and with sudanblack B and lacking or only weak staining for nonspecific esterase. In 8 patients the leukemic myeloblasts additionally showed distinct granular staining for polysaccharides using the PAS-reaction. The therapeutic response, the remission rate and the survival time of these 8 cases have been compared to those of 40 patients, whose leukemic myeloblasts differed exclusively in the absence of granular PAS-positive materials. Out of the latter PAS-negative cases 7 patients (18%) went into a complete remission (M1, P1), 5 patients achieved partial remission (M2, P1-2), the 50%-survival time was 4.9 months. Out of the 8 granular PAS-positive cases 4 patients (50%) went into complete (M1, P1), and 1 reached partial remission (M2, P1-2). The 50%-survival time of the cases now lasts 10.1 months and three patients are still alive and in persisting complete remission 19, 12.5 and 12 months after diagnosis. These results suggest a better prognosis and an improved therapeutic response in those myeloblastic leukemias which additionally contain cytoplasmic granular PAS-positive materials.     

Cell-mediated immunity in human acute myeloblastic leukemia

Summary Lymphocyte stimulation tests with autologous myeloblasts were performed in 31 patients with nonlymphatic acute leukemia. Twenty-five patients were receiving chemotherapy combined with immunotherapy; six received chemotherapy only. Thirteen nonleukemic patients with various disorders and six healthy control patients were also studied.It was found that 4/15 patients in 9/38 tests had autologous lymphocytes stimulated by autologous circulating myeloblasts. Bone marrow cells also effected stimulation, significantly more often if the marrow was taken in relapse than when it was taken in remission.However, so-called immunotherapy with allogeneic leukemic myeloblasts and BCG could not be shown to increase these frequencies. Nor did it significantly increase the degree of stimulation measured as DNA synthesis in lymphocytes.Moreover, nonleukemic bone marrow cells from patients with other disorders also stimulated autologous lymphocytes in 1/13 patients. No recognition of autologous myeloblasts was observed when the responding lymphocytes were taken in incomplete remission or during the month preceding relapse.with the technical assistance of T. Lehtinen and A. M. SjögrenSupported by the Swedish Cancer Research Foundation Grant no. 699-B76-04XA     

Immunotherapy for remission maintenance in acute myeloblastic leukemia

Summary Forty-eight patients with acute myeloblastic leukemia in remission were treated with immunotherapy in addition to remission-maintenance chemotherapy. The first 16 patients were treated with weekly BCG and a leukemia cell vaccine (group 1). The next 32 patients were randomly allocated to receive BCG and a leukemia cell vaccine given once monthly (group 2) or BCG given monthly with no leukemia cell vaccine (group 3). There was no significant difference in remission duration or survival between the randomly allocated groups (2 and 3).Comparisons with group 1 are limited by the non-random allocation to this group, but selection bias was unlikely and clinical features were similar in the three patient groups. No significant difference in remission duration or survival was seen amongst the three groups studied. There was no advantage in the addition of leukemia cell vaccine (groups 1 and 2) to BCG alone (group 3) and no advantage to weekly (group 1) versus monthly immunotherapy (groups 2 and 3). Only 7 of the 48 patients achieved a second remission, and 4 of these were short-term partial remissions.The following are contributing members of the Toronto Leukemia Study Group: Doctor's Hospital, Harvey Silver MD; Humber Memorial Hospital, Alan Seidenfeld MD; Mississauga Hospital, Michael King MD; Mount Sinai Hospital, Dominic Amato MD; Northwestern Hospital, Wilhelm Kwant MD; Oshawa General Hospital, Hak Chiu MD; St Michael's Hospital, Bernadette Garvey MD, Kenneth Butler MD; St Joseph's Hospital, H. James Watt MD, Murray Davidson MD; Toronto General Hospital, Gerald Scott MD, William Francombe MD, Kenneth Shumak MD; John Crookston MD, PhD; Toronto Western Hospital, James G. Watt MD, David Sutton MD; Michael Baker MD; Domenic Pantalony MD; Wellesley Hospital, Dale Dotten MD; Women's College Hospital, George Kutas MD; York Finch Hospital, Sam Berger MD     

Disturbances of desmofibrinogenesis in pateints suffering from acute myeloblastic leukemia

Significantly decreased levels of blood plasma clotting factor XIII (FSF) were found in the blood of 20 patients with acute myeloblastic leukemia as compared to the control values. It was found that after administration of cytostatic drugs (Cerubidyne and Cytosar) FSF deficiency was higher. This effect was associated with a proteolytic activity detectable in plasma which destroys FSF in vitro. This proteolytic activity was neither inhibited by EACA nor by Trasylol. These results indicate that in patients with acute myeloblastic leukemia beside DIC the treatment with cytostatic drugs as well as the presence of proteases from leukemic cells in the plasma will cause an impairment of transformation of soluble fibrin polymer into insoluble desmofibrin.     

A mathematical model of the chemotherapeutic treatment of acute myeloblastic leukemia.

Based on our previous mathematical model of the acute myeloblastic leukemic (AML) state in man, we superimpose a chemotherapeutic drug treatment regimen. Our calculations suggest that small changes in the protocol can have significant effects on the result of treatment. Thus, the optimal period between drug doses is the S-phase interval of the leukemic cells--about 20h--and the greater the number of doses administered in a given course treatment, the longer the rest interval should be before the next course is administered. For a patient with a "slow" growing AML cell population, remission can be achieved with one or two courses of treatment, and further suppression of the leukemic population can be achieved with continued courses of treatment. However, for patients with a "fast" growing AML cell population, a similar aggressive treatment regimen succeeds in achieving remission status only at the cost of very great toxic effects on the normal neutrophil population and its precursors.     

Computed tomographic symptomatology of lymphedema of the lower extremities]

CT potentialities in the diagnosis and differential diagnosis of lower limb lymphedema in 40 patients (11 men and 29 women), aged 16 to 56, are illustrated. Eighty studies on the limbs were performed to 20 patients with primary lymphedema, 6 with congenital lymphedema, 26 with secondary lymphedema, and 28 with unaffected limbs. The data were statistically processed according to the following parameters: leg diameter, skin and subcutaneous fat thickness and density, the presence of fibrosis in subcutaneous fat, its localization, shape and spreading, fascial thickness. CT permitted objective assessment of disease and a right choice of a type of surgical intervention.     

Acute myeloblastic leukemia considered as a clonal hemopathy.

Acute myeloblastic leukemia, like certain other hematologic disorders, originates in pluripotent stem cells. Two general biologic processes underlie development of the disease. Over long times, clonal progression leads from normal polyclonal hemopoiesis through clonal preleukemia to leukemia. Overt leukemia is characterized by the emergence of blast cell populations. Over shorter times, clonal expansion yields cellular diversity based upon randomizing events. The analysis indicates that that blast population is of crucial importance. Characteristics of a colony assay for blast cell progenitors are presented.     

Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans

Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.