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Hypersplenism is characterized by cytopenia, splenomegaly (possibly hyperplastic bone-marrow), and lienal hypersequestration. It is necessary, in view of the rather important surgical risks of splenectomy, to clarify if the hypersplenism may be influenced by splenic irradiation in case of chronic myeloid leukemia (CML) or chronic lymphatic leukemia (CLL). References in literature are rare and do not present a reliable differentiation of the syndrome, according to its present definition. Of our patients, three cases with hypersplenism verified by radioiron studies are reported: in one patient with chronic myeloid leukemia, irradiation of the spleen had no effect, whereas pancytopenia was completely repaired by means of splenectomy. The same results were seen in a patient with chronic lymphatic leukemia. In the last patient, however, who had chronic lymphatic leukemia, fractionated irradiation of the spleen led to a distinct improvement of anemia and thrombopenia, but the recovery lasted only six months. This effect is due to transient normalization of the lienal hypersequestration.
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BALB/c mice depleted of T-cells by thymectomy at 3 to 5 days of age and by treatment with antithymocyte serum were inoculated with the lymphatic leukemia virus derived from Friend virus. After a long latent period, these animals developed erythroid leukemia. In contrast, intact control mice inoculated with Friend virus-associated lymphatic leukemia virus developed typical thymic (T-cell) lymphomas. Cell-free virus prepared from leukemic T-cell-depleted animals induced lymphoid, myeloid, and erythroid leukemias in intact mice. The erythroid leukemia-inducing virus differed from the spleen focus-forming component of Friend virus in its long latent period (88 to 225 days) and in its inability to induce spleen foci. End-point dilution experiments suggested that a hitherto undescribed component of the Friend virus complex might be responsible for these late-appearing erythroid leukemias.
Chronic lymphatic leukemia (CLL) is a disease with a prognosis that has previously been difficult to assess. In recent years, this problem has largely been overcome by various classifications based on clinical and hematologic findings. This article presents the results of a study designed to show the value of lymphograms in assessing the prognosis. These results show that prognosis is associated with lymph node structure, as assessed by lymphography. Lymphography, as an investigation is superior to scanning or echography, since these give information merely on nodal size. It is proposed that lymphograms should be used for assessing the gravity of the disease and help in the choice of therapy.
Acute lymphatic leukemias, expressing the common acute leukemia antigen were investigated for expression of early T- and B-cell associated markers and the activation of the gene for the heavy chain of the immunoglobulin M. The gene activation as determined by quantification of the mu mRNA with a fluorochrome labeled gene probe in situ in individual cells showed a wide spectrum of positivity which was correlated to increasing expression of B-maturation markers. There was also a correlation between the amount of cellular immunoglobulin as determined by immunofluorimetry. Quantitation of mRNA in individual cells may allow to determine the degree of gene activation in antigenically defined individual cells and may thus contribute a new tool for classification of normal and malignant cells.
Acute lymphatic leukemia (common-ALL-Ag positive) was found to be the underlying disease in a 4-year-old boy with arthropathy, generalized rash and marked eosinophilia. ALL may be overlooked in the early stages. Cytochemical, chromosomal and immunological markers are needed to distinguish it from other leukemias. As shown by the data of 25 patients from the literature, hypereosinophilic syndrome (HES) influences morbidity and lethality. Hydroxyurea rapidly lowers the eosinophil counts and may therefore prevent the cardiac involvement typical of HES.
The methylation state of CCGG sites in and around the human ornithine decarboxylase gene, oncogenes c-myc and erb-A1, and actin genes were determined in human malignant leucocytes from patients with acute and chronic myeloid leukemia, chronic lymphatic leukemia, polycythemia vera, and multiple myeloma by means of isoschizomeric restriction endonuclease analysis. When compared with DNA from leucocytes of healthy controls, the ornithine decarboxylase and erb-A1 genes were substantially hypomethylated in all samples obtained from patients with chronic lymphatic leukemia. Hypomethylation of genes, particularly growth-related sequences, might be a crucial fact in the malignant transformation of human leucocytes. Its relatively simple detection from blood samples may prove clinically applicable in monitoring patients with chronic lymphatic leukemia.
Alkaline phosphatase [orthophosphoricmonoester phosphohydrolase (alkaline pH optimum), EC 3.1.3.1] purified from a Burkitt lymphoma cell line (Daudi) and Moloney-virus-induced murine leukemia (YAC) showed unique catalytic properties in substrate specificity and inhibition by cysteamine-S-phosphate. It migrated on polyacrylamide gel electrophoresis in a single activity band. Alkaline phosphatase with similar properties was found in several human lymphoblastoid cell lines, in chronic lymphatic leukemic cells, in organs of leukemic mice, and in sera of patients with certain lymphoproliferative disorders.
In chronic lymphatic leukemia lymph nodes show very often nodular aggregates of cells that are somewhat larger than small lymphocytes and that are less hyperchromatic and less closely packed. These aggregates appear histologically as light areas that are called pseudofollicles, pseudonodules or proliferation centers. However, it has not been substantiated as yet that a more active proliferation of cells indeed takes place within these areas. Therefore, in 10 cases of chronic lymphatic leukemia the DNA-content, the size of the nuclei, and the frequency of mitoses within and outside the pseudofollicles were assessed. It could be shown that the cells of the pseudofollicles are indeed more actively proliferating populations than the cells outside the pseudofollicles. This proves that pseudofollicles are proliferation centers.
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Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously ex vivo purged of the leukemia cells with mafosfamide (ASTA Z7654) and stored in liquid nitrogen. Eight weeks after cytoreductive therapy and bone marrow transplantation we tried to immunize the mice against the lethal dose of the leukemia by i.p. injections of L1210-Maf cells (L1210 cells treated in vitro with mafosfamide for inhibition of their growth). About 75% of such mice were able to reject the subsequent 10(3) L1210 leukemia cell challenge, as compared with 70% of normal immunized mice and 55% of mice reconstituted with bone marrow cells not treated with mafosfamide.
In chronic lymphatic leukemia there are also leukemic changes in the gastrointestinal tract; these can be detected roentgenologically and endoscopically.
Acute lymphatic leukemia presenting with bone pain and spine involvement is a recognized clinicopathologic complex that can mimic a wide range of orthopaedic conditions. Bone pain as the presenting complaint is common, with a reported incidence of 27% to 50%. Radiologic abnormalities associated with leukemia in children has been described previously. In the literature, the incidence of spinal involvement is controversial, but there is agreement that the spine is less commonly involved than are the long bones. At the onset of the disease, only 10% of children have normal peripheral blood counts. If the patient has spinal involvement and a normal leukocyte count, the diagnosis is often unclear. Only three of these patients have been described in the literature; this article adds one more patient with acute lymphatic leukemia with back pain as the main symptom, vertebral collapse, and a normal peripheral blood cell count at the time of initial presentation. It illustrates that delay in diagnosis frequently occurs, with the classic features of the disease being uniformly absent.