A case of preleukemia--reconstitution of normal marrow function after bone marrow transplantation (BMT) from identical twin.
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Biomedical subjects
Publications and source records attributed to B Kubanek.
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A 3-year-old boy (patient A) with a congenital and a 24-year-old man (patient B) with an acquired granulocyte function defect received supportive granulocyte transfusions for the management of severe infections. The boy had suffered from recurrent infections since bith. His granulocytes showed in vitro almost no chemotactic responsiveness, an impaired phagocytosis and reduced intracellular killing of Candida albicans. Family studies suggested that it was an inherited autosomal recessive defect. The child developed a Pseudomonas pneumonia at the age of 3 years, which did not respond to antibiotic therapy. Granulocyte transfusions were then started and soon after the fever and pneumonia disappeared. Patient B showed the haematological signs of a preleukaemic state. He had 3 recurrent episodes of furunculosis which led each time to cellulitis and septic temperatures accompanied by symptoms of an enterocolitis. Tests of granulocyte function in vitro showed reduced intracellular killing of Staphylococcus aureus. Granulocyte transfusions were started, since no clinical improvement could be attained by antibiotics. With transfusion therapy, fever, cellulitis and enterocolitis disappeared each time.
60 adult patients with acute leukemia (AL) previously untreated or in relapse received induction chemotherapy with different types of supportive care. Group A was decontaminated by nonabsorbable antibiotics in strict reverse isolation, group B was isolated only and group C was treated under routine hospital conditions. There were less infections in group A and B compared with group C. 76% of patients in group A achieved remission, in contrast to 57% in group B and 59% in group C. Late evaluation three years after termination of the study showed that all patients were dead except four patients being in first remission after discontinuation of maintenance treatment. Three patients were treated in group A, one patient in group C. However, the differences of survival and remission rates were not significant. Failure to demonstrate significant advantage of isolation and decontamination in treatment of AL was caused by insufficient suppression of microbes by the applied antimicrobial measures. Thus, it is suggested to investigate better antimicrobial treatment before gnotobiotic care is accepted as routine supportive treatment in AL.
Possible variation in proliferative state among subpopulations of myelopoietic progenitor cells of mouse bone marrow (CFU-c), which form in vitro colonies of granulocytes and/or macrophages, was investigated by estimation of the percentage in S phase of the cell cycle. Subpopulations of CFU-c, obtained by separation of femoral marrow cells on continuous albumin density gradients, were detected by culture in agar with different types of colony stimulating factor (CSF). The percentage of CFU-c in S phase, detected with mouse lung conditioned medium (CSFMLCM), averaged 17%. This was significantly lower than the 41% which was found when an extract of human urine (CSFHU) was used. This result was obtained with unfractionated marrow cells both by in vitro suicide with tritiated thymidine and by in vivo administration of hydroxyurea. There were different CFU-c responses to CSF, on the basis of their density distributions. Those responding to CSFMLCM had a low density disposition whereas the CSFHU responders had a high density disposition. The administration of hydroxyurea resulted in an alteration in the density distribution which indicated that a larger proportion of high density CFU-c were in S phase. The results indicate that CFU-c responding to different types of CSF differ in buoyant density and proliferative state.
Employing the erythroid colony-forming technique, it is shown that throughout hepatic erythropoiesis in the mouse, the CFU-E population remains sensitive to erythropoietin. Maximum stimulation was achieved during this period using an erythropoietin concentration of 0.075 units/ml. The peak in the CFU-E concentration occurs between the 11th and 12th day while absolute values show a maximum on the 14th day of gestation. These results are discussed in terms of changing cell populations, both of erythropoietic precursors and hepatocytes from which it is concluded that at no time during foetal erythropoiesis does the CFU-E population change or become unresponsive to erythropoietin. The BFU-E population follows closely that of the CFU-E, but declines about 24 h earlier on the 16th day of gestation. The effect of the foetus on the mother was also studied during the second half of pregnancy. During this period of natural perturbation both femoral and, in particular, splenic erythropoiesis are increased. However, during this time an erythropoietin concentration of 0.3 units/ml was required to maximally stimulate the CFU-E population derived from these tissues. The fact that both adult and foetal erythroid tissue maintain a rather constant requirement for erythropoietin for their growth in vitro, indicates that it is an intrinsic property of the cells. It is concluded that increased maternal erythropoiesis is due to an increased oxygen requirement causing hypoxia due to the growing foetus.
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In two patients with acute leukaemia, the development of progressive interstitial pulmonary fibrosis was observed following chemotherapy with BCNU, Cytoxan and Ara-C. The x-ray changes were accompanied by restrictive changes of pulmonary function and, later on, by severe hypoxia. Serologic tests did not reveal infection with cytomegaly virus or mycoplasma pneumoniae. These findings, together with reports in the literature, suggest a toxic effect of BCNU on the lung. The combination with Cyclophosphamide may contribute to this toxic reaction.
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Thirty patients with severe drug-induced agranulocytosis were admitted to the Ulm University Hospital between January, 1968 and October, 1976. All of 13 already infected patients treated with antimicrobial decontamination in a plastic isolation bed system survived. But nine of 17 patients treated in the open ward died. The cases were not randomised and there was a difference in age between the two groups, but nevertheless the results suggest that antimicrobial decontamination and isolation is superior to treatment in an open ward.
Medium conditioned by mouse heart tissue was found to contain colony-stimulating factor(s) (CSF) which produced in vitro colonies of granulocytes and/or macrophages with bone marrow cells of CBA mice. The action of this CSF type (CSFMHCM) was compared with that of post-endotoxin mouse serum (CSFES on colony formation by density subpopulations of colony-forming cells (CFU-c), separated by isopycnic centrifugation in a continous albumin density gradient. The number, size and morphology of colonies were examined. Mouse heart conditioned medium produced slightly more colonies and of larger size than endotoxin serum but the density distribution of their CFU-c were similar. Low density CFU-c produced predominately pure granulocytic colonies and high density ones predominately pure macrophage colonies with both types of CSF. There was no apparent relationship between colony size and CFU-c density.
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Nine patients with anorexia nervosa were studied, who had varying degrees of bone marrow failure ranging from a slight neutropenia to severe pancytopenia. In addition to routine laboratory work bone marrow biopsies were performed at admission and during the course of disease. In four of those patients erythropoietin excretion per 24 hours was measured by the bioassay in the polycythemic mouse at least twice during the course of treatment. At admission most bone marrow showed a marked although varying hypocellularity with grossly apparant background gelatinous material, which appeared to consist of acid mucopolysaccharides. Leukopenia and the changes of the bone marrow morphology reversed to normal after refeeding. Erythropoietin excretion was only elevated in patients who were anemic and returned to normal when the haematocrit reached normal levels. It seems therefore unlikely that an impaired production of erythropoietin or other postulated humoral factors cause the haemopoietic changes in anorexia nervosa. A direct effect of fat or carbohydrate depletion and/or of the increased mucopolysaccharides upon the proliferation of the haemopoietic cells can be suggested, but is an entirely speculative preposition.
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